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Gene Information

Gene symbol: INS

Gene name: insulin

HGNC ID: 6081

Related Genes

# Gene Symbol Number of hits
1 AANAT 1 hits
2 ABCA1 1 hits
3 ABCA4 1 hits
4 ABCB11 1 hits
5 ABCC8 1 hits
6 ABCG1 1 hits
7 ABCG2 1 hits
8 ABHD6 1 hits
9 ABL2 1 hits
10 ABO 1 hits
11 ABR 1 hits
12 ABRA 1 hits
13 ACACA 1 hits
14 ACAD10 1 hits
15 ACADL 1 hits
16 ACADM 1 hits
17 ACADS 1 hits
18 ACCN3 1 hits
19 ACCS 1 hits
20 ACE 1 hits
21 ACE2 1 hits
22 ACHE 1 hits
23 ACLY 1 hits
24 ACO1 1 hits
25 ACOT1 1 hits
26 ACP1 1 hits
27 ACP5 1 hits
28 ACPP 1 hits
29 ACSL1 1 hits
30 ACSL5 1 hits
31 ACSL6 1 hits
32 ACSS2 1 hits
33 ACTB 1 hits
34 ACTR1A 1 hits
35 ACVR1B 1 hits
36 ACVR1C 1 hits
37 ADA 1 hits
38 ADAM17 1 hits
39 ADAMTS9 1 hits
40 ADCY1 1 hits
41 ADCY10 1 hits
42 ADCY5 1 hits
43 ADCY7 1 hits
44 ADCYAP1 1 hits
45 ADFP 1 hits
46 ADH1A 1 hits
47 ADIPOQ 1 hits
48 ADIPOR1 1 hits
49 ADIPOR2 1 hits
50 ADK 1 hits
51 ADRA1D 1 hits
52 ADRA2A 1 hits
53 ADRB2 1 hits
54 ADRB3 1 hits
55 ADRBK1 1 hits
56 AGRP 1 hits
57 AGT 1 hits
58 AGTR1 1 hits
59 AGTR2 1 hits
60 AGTRL1 1 hits
61 AGXT 1 hits
62 AHI1 1 hits
63 AHR 1 hits
64 AHSG 1 hits
65 AIRE 1 hits
66 AKR1B1 1 hits
67 AKR1C1 1 hits
68 AKT1 1 hits
69 AKT1S1 1 hits
70 AKT2 1 hits
71 ALB 1 hits
72 ALDH1A3 1 hits
73 ALDH7A1 1 hits
74 ALDOB 1 hits
75 ALMS1 1 hits
76 ALOX12 1 hits
77 ALPI 1 hits
78 ALPP 1 hits
79 ALX3 1 hits
80 ANG 1 hits
81 ANGPT1 1 hits
82 ANGPT2 1 hits
83 ANGPTL2 1 hits
84 ANGPTL4 1 hits
85 ANK3 1 hits
86 ANKRD23 1 hits
87 ANXA5 1 hits
88 AOC3 1 hits
89 AP2B1 1 hits
90 APLN 1 hits
91 APLP2 1 hits
92 APOA1 1 hits
93 APOB 1 hits
94 APOC3 1 hits
95 APOE 1 hits
96 APP 1 hits
97 APPL1 1 hits
98 AQP5 1 hits
99 AQP7 1 hits
100 AQP9 1 hits
101 AR 1 hits
102 ARD1A 1 hits
103 ARHGEF11 1 hits
104 ARNT 1 hits
105 ART2P 1 hits
106 ASIP 1 hits
107 ASPM 1 hits
108 ATF2 1 hits
109 ATF3 1 hits
110 ATF6 1 hits
111 ATIC 1 hits
112 ATM 1 hits
113 ATN1 1 hits
114 ATP2A3 1 hits
115 ATP2B4 1 hits
116 ATP6V1H 1 hits
117 AVP 1 hits
118 AXPC1 1 hits
119 AZGP1 1 hits
120 B2M 1 hits
121 BACE1 1 hits
122 BAX 1 hits
123 BCHE 1 hits
124 BCL2 1 hits
125 BCL2A1 1 hits
126 BCL2L1 1 hits
127 BDNF 1 hits
128 BGLAP 1 hits
129 BHLHB2 1 hits
130 BHMT 1 hits
131 BIRC5 1 hits
132 BLM 1 hits
133 BMP3 1 hits
134 BMP4 1 hits
135 BMP7 1 hits
136 BMPR2 1 hits
137 BRD2 1 hits
138 BRS3 1 hits
139 BTC 1 hits
140 BTG2 1 hits
141 C20orf181 1 hits
142 C8orf4 1 hits
143 CACNA1D 1 hits
144 CALCA 1 hits
145 CAMK2G 1 hits
146 CANX 1 hits
147 CAPN10 1 hits
148 CASP3 1 hits
149 CASP9 1 hits
150 CASR 1 hits
151 CAT 1 hits
152 CAV1 1 hits
153 CBL 1 hits
154 CBR1 1 hits
155 CBS 1 hits
156 CBX4 1 hits
157 CCK 1 hits
158 CCL11 1 hits
159 CCL2 1 hits
160 CCL3 1 hits
161 CCL5 1 hits
162 CCL8 1 hits
163 CCNB1 1 hits
164 CCND1 1 hits
165 CCR2 1 hits
166 CCR5 1 hits
167 CCRK 1 hits
168 CCT 1 hits
169 CD14 1 hits
170 CD300C 1 hits
171 CD36 1 hits
172 CD38 1 hits
173 CD4 1 hits
174 CD40 1 hits
175 CD40LG 1 hits
176 CD46 1 hits
177 CD47 1 hits
178 CD5 1 hits
179 CD59 1 hits
180 CD68 1 hits
181 CD69 1 hits
182 CD79A 1 hits
183 CD79B 1 hits
184 CD80 1 hits
185 CD83 1 hits
186 CD86 1 hits
187 CD8A 1 hits
188 CDK2 1 hits
189 CDK4 1 hits
190 CDK5 1 hits
191 CDK5R1 1 hits
192 CDKAL1 1 hits
193 CDKN1A 1 hits
194 CDX2 1 hits
195 CEACAM1 1 hits
196 CEBPA 1 hits
197 CEL 1 hits
198 CES1 1 hits
199 CETP 1 hits
200 CFD 1 hits
201 CFDP1 1 hits
202 CHAT 1 hits
203 CHPT1 1 hits
204 CISH 1 hits
205 CKB 1 hits
206 CKM 1 hits
207 CLCN3 1 hits
208 CLPS 1 hits
209 CLU 1 hits
210 CNBP 1 hits
211 CNR1 1 hits
212 CNR2 1 hits
213 CNTF 1 hits
214 COL18A1 1 hits
215 COL1A1 1 hits
216 COL1A2 1 hits
217 COL1AR 1 hits
218 COL4A4 1 hits
219 COQ6 1 hits
220 COQ9 1 hits
221 COX11 1 hits
222 COX7A1 1 hits
223 COX8A 1 hits
224 CP 1 hits
225 CPA6 1 hits
226 CPB2 1 hits
227 CPE 1 hits
228 CPT1A 1 hits
229 CRABP1 1 hits
230 CREB1 1 hits
231 CREBBP 1 hits
232 CREM 1 hits
233 CRH 1 hits
234 CRK 1 hits
235 CRP 1 hits
236 CRTC1 1 hits
237 CRTC2 1 hits
238 CS 1 hits
239 CSH1 1 hits
240 CSN2 1 hits
241 CSNK2A1 1 hits
242 CSNK2B 1 hits
243 CST3 1 hits
244 CTBS 1 hits
245 CTGF 1 hits
246 CTLA4 1 hits
247 CTNNB1 1 hits
248 CTSD 1 hits
249 CTSK 1 hits
250 CTSL1 1 hits
251 CXCL10 1 hits
252 CXCL2 1 hits
253 CYB5A 1 hits
254 CYBA 1 hits
255 CYBB 1 hits
256 CYCS 1 hits
257 CYGB 1 hits
258 CYP19A1 1 hits
259 CYP1A1 1 hits
260 CYP2B6 1 hits
261 CYP2E1 1 hits
262 CYP2J2 1 hits
263 CYP3A 1 hits
264 CYP7A1 1 hits
265 CYSLTR2 1 hits
266 DBH 1 hits
267 DBI 1 hits
268 DBP 1 hits
269 DDIT3 1 hits
270 DDIT4 1 hits
271 DEDD 1 hits
272 DGAT1 1 hits
273 DGKB 1 hits
274 DGKQ 1 hits
275 DLK1 1 hits
276 DNAJB1 1 hits
277 DOK1 1 hits
278 DPP4 1 hits
279 DUOX1 1 hits
280 DUSP1 1 hits
281 DUSP6 1 hits
282 DUSP9 1 hits
283 E2F1 1 hits
284 EDC3 1 hits
285 EDN1 1 hits
286 EDNRA 1 hits
287 EDNRB 1 hits
288 EGF 1 hits
289 EGFR 1 hits
290 EGR1 1 hits
291 EIF2A 1 hits
292 EIF2AK2 1 hits
293 EIF2AK3 1 hits
294 EIF2B1 1 hits
295 EIF2S1 1 hits
296 EIF4E 1 hits
297 EIF4EBP1 1 hits
298 ELSPBP1 1 hits
299 ENO2 1 hits
300 ENPP1 1 hits
301 ENPP2 1 hits
302 ENTPD2 1 hits
303 EP300 1 hits
304 EPHB2 1 hits
305 EPHX2 1 hits
306 EPO 1 hits
307 EPOR 1 hits
308 ERBB2 1 hits
309 ERBB3 1 hits
310 ERCC2 1 hits
311 ESR1 1 hits
312 ESR2 1 hits
313 ESRRB 1 hits
314 ETV5 1 hits
315 F2 1 hits
316 F7 1 hits
317 FAAH 1 hits
318 FABP2 1 hits
319 FABP4 1 hits
320 FABP5 1 hits
321 FADS1 1 hits
322 FADS2 1 hits
323 FADS3 1 hits
324 FAM3B 1 hits
325 FAS 1 hits
326 FASN 1 hits
327 FBP2 1 hits
328 FEV 1 hits
329 FFAR1 1 hits
330 FGF19 1 hits
331 FGF2 1 hits
332 FGF21 1 hits
333 FKBP11 1 hits
334 FKBP1A 1 hits
335 FLNA 1 hits
336 FOS 1 hits
337 FOSB 1 hits
338 FOXA2 1 hits
339 FOXC1 1 hits
340 FOXC2 1 hits
341 FOXM1 1 hits
342 FOXO1 1 hits
343 FOXO3 1 hits
344 FOXO4 1 hits
345 FOXO6 1 hits
346 FOXP3 1 hits
347 FTO 1 hits
348 FUCA1 1 hits
349 FURIN 1 hits
350 G6PC 1 hits
351 G6PC2 1 hits
352 G6PD 1 hits
353 GAA 1 hits
354 GAB1 1 hits
355 GAB2 1 hits
356 GABBR1 1 hits
357 GABPA 1 hits
358 GABRE 1 hits
359 GAD1 1 hits
360 GAD2 1 hits
361 GADD45B 1 hits
362 GAL 1 hits
363 GAP43 1 hits
364 GAPDH 1 hits
365 GAS6 1 hits
366 GAST 1 hits
367 GC 1 hits
368 GCG 1 hits
369 GCGR 1 hits
370 GCK 1 hits
371 GCLC 1 hits
372 GDNF 1 hits
373 GFAP 1 hits
374 GGT1 1 hits
375 GHR 1 hits
376 GHRH 1 hits
377 GHRL 1 hits
378 GIP 1 hits
379 GIPR 1 hits
380 GJB1 1 hits
381 GLIS3 1 hits
382 GLP1R 1 hits
383 GNAI2 1 hits
384 GNAS 1 hits
385 GNAT3 1 hits
386 GNRH1 1 hits
387 GOLGA6 1 hits
388 GORASP1 1 hits
389 GPA33 1 hits
390 GPBAR1 1 hits
391 GPER 1 hits
392 GPI 1 hits
393 GPR119 1 hits
394 GPR120 1 hits
395 GPR176 1 hits
396 GPR39 1 hits
397 GPR55 1 hits
398 GPR77 1 hits
399 GPT 1 hits
400 GPX1 1 hits
401 GRB10 1 hits
402 GRB2 1 hits
403 GRIN2B 1 hits
404 GRP 1 hits
405 GSK3A 1 hits
406 GSK3B 1 hits
407 GSR 1 hits
408 GSTA1 1 hits
409 GSTA4 1 hits
410 GSTCD 1 hits
411 GSTK1 1 hits
412 GYPE 1 hits
413 H19 1 hits
414 H6PD 1 hits
415 HADH 1 hits
416 HBA1 1 hits
417 HBB 1 hits
418 HCRT 1 hits
419 HDAC9 1 hits
420 HEXA 1 hits
421 HEXB 1 hits
422 HFE 1 hits
423 HGF 1 hits
424 HGS 1 hits
425 HHEX 1 hits
426 HIF1A 1 hits
427 HIRA 1 hits
428 HIST2H2BE 1 hits
429 HK2 1 hits
430 HLA-A 1 hits
431 HLA-B 1 hits
432 HLA-DQA2 1 hits
433 HLA-DQB1 1 hits
434 HLA-DRB1 1 hits
435 HLA-F 1 hits
436 HMGB1 1 hits
437 HMGCR 1 hits
438 HMOX1 1 hits
439 HMX1 1 hits
440 HNF1A 1 hits
441 HNF1B 1 hits
442 HNF4A 1 hits
443 HP 1 hits
444 HPSE 1 hits
445 HRB 1 hits
446 HSD11B1 1 hits
447 HSD17B6 1 hits
448 HSF1 1 hits
449 HSPA1A 1 hits
450 HSPA1B 1 hits
451 HSPA5 1 hits
452 HSPD1 1 hits
453 HSPE1 1 hits
454 HTL 1 hits
455 HTR2B 1 hits
456 HTT 1 hits
457 IAPP 1 hits
458 ICA1 1 hits
459 ICAM1 1 hits
460 ID1 1 hits
461 IDDM2 1 hits
462 IDE 1 hits
463 IDS 1 hits
464 IFI44 1 hits
465 IFN1 1 hits
466 IFNA1 1 hits
467 IFNG 1 hits
468 IGF1 1 hits
469 IGF1R 1 hits
470 IGF2 1 hits
471 IGF2BP2 1 hits
472 IGFBP1 1 hits
473 IGFBP2 1 hits
474 IGFBP3 1 hits
475 IGFBP4 1 hits
476 IGFBP5 1 hits
477 IGFBP7 1 hits
478 IGKV1-17 1 hits
479 IHG1 1 hits
480 IKBKB 1 hits
481 IL10 1 hits
482 IL13 1 hits
483 IL18 1 hits
484 IL1A 1 hits
485 IL1B 1 hits
486 IL1RN 1 hits
487 IL2 1 hits
488 IL24 1 hits
489 IL2RA 1 hits
490 IL2RG 1 hits
491 IL4 1 hits
492 IL6 1 hits
493 IL6R 1 hits
494 IL6ST 1 hits
495 IL8 1 hits
496 ILK 1 hits
497 IMMT 1 hits
498 INHBE 1 hits
499 INPP5D 1 hits
500 INPPL1 1 hits
501 INSR 1 hits
502 INSRR 1 hits
503 IRF1 1 hits
504 IRS1 1 hits
505 IRS2 1 hits
506 IRS4 1 hits
507 IRX6 1 hits
508 ISL1 1 hits
509 ITGAX 1 hits
510 ITLN1 1 hits
511 ITPR3 1 hits
512 JAK2 1 hits
513 JAZF1 1 hits
514 JPH3 1 hits
515 JUN 1 hits
516 KCNJ11 1 hits
517 KCNJ3 1 hits
518 KCNJ4 1 hits
519 KCNQ1 1 hits
520 KDR 1 hits
521 KIAA1524 1 hits
522 KIF5B 1 hits
523 KITLG 1 hits
524 KLF11 1 hits
525 KLK1 1 hits
526 KLK3 1 hits
527 KLRG1 1 hits
528 KNG1 1 hits
529 KRT124P 1 hits
530 KRT19 1 hits
531 LAMB1 1 hits
532 LBP 1 hits
533 LCAT 1 hits
534 LCN2 1 hits
535 LDLR 1 hits
536 LEP 1 hits
537 LEPR 1 hits
538 LIPA 1 hits
539 LIPC 1 hits
540 LIPE 1 hits
541 LMF1 1 hits
542 LMNA 1 hits
543 LNPEP 1 hits
544 LONP1 1 hits
545 LPAL2 1 hits
546 LPIN1 1 hits
547 LPIN2 1 hits
548 LPL 1 hits
549 LPO 1 hits
550 LRP1 1 hits
551 LRP5 1 hits
552 LRP6 1 hits
553 LTA 1 hits
554 LTB4R 1 hits
555 LTF 1 hits
556 MADD 1 hits
557 MAFA 1 hits
558 MAFB 1 hits
559 MAP2K1 1 hits
560 MAP3K1 1 hits
561 MAP3K14 1 hits
562 MAP3K5 1 hits
563 MAP3K8 1 hits
564 MAPK1 1 hits
565 MAPK10 1 hits
566 MAPK14 1 hits
567 MAPK3 1 hits
568 MAPK6 1 hits
569 MAPK8 1 hits
570 MAPK9 1 hits
571 MAPT 1 hits
572 MB 1 hits
573 MBP 1 hits
574 MC4R 1 hits
575 MCF2 1 hits
576 MCF2L2 1 hits
577 MCHR1 1 hits
578 MCL1 1 hits
579 MDH2 1 hits
580 ME1 1 hits
581 MEF2A 1 hits
582 MEN1 1 hits
583 MET 1 hits
584 MGEA5 1 hits
585 MGST3 1 hits
586 MIF 1 hits
587 MIRN145 1 hits
588 MIRN146A 1 hits
589 MIRN15A 1 hits
590 MIRN212 1 hits
591 MIRN29A 1 hits
592 MIRN33A 1 hits
593 MIRN375 1 hits
594 MIRN96 1 hits
595 MKI67 1 hits
596 MLN 1 hits
597 MLX 1 hits
598 MLXIPL 1 hits
599 MME 1 hits
600 MMP12 1 hits
601 MMP2 1 hits
602 MMP7 1 hits
603 MMP9 1 hits
604 MOG 1 hits
605 MPFD 1 hits
606 MPG 1 hits
607 MSC 1 hits
608 MSI1 1 hits
609 MSI2 1 hits
610 MSTN 1 hits
611 MT3 1 hits
612 MTNR1A 1 hits
613 MTNR1B 1 hits
614 MTPN 1 hits
615 MTTP 1 hits
616 MYC 1 hits
617 MYD88 1 hits
618 MYH14 1 hits
619 MYH7 1 hits
620 MYLK 1 hits
621 NAGLU 1 hits
622 NAMPT 1 hits
623 NCAM1 1 hits
624 NCK1 1 hits
625 NCL 1 hits
626 NCOR1 1 hits
627 NDN 1 hits
628 NDUFA10 1 hits
629 NDUFB4 1 hits
630 NES 1 hits
631 NEU1 1 hits
632 NEUROD1 1 hits
633 NEUROG3 1 hits
634 NFE2L2 1 hits
635 NFKB1 1 hits
636 NFKBIA 1 hits
637 NGF 1 hits
638 NIDDM2 1 hits
639 NIT1 1 hits
640 NKX6-1 1 hits
641 NLRP3 1 hits
642 NM 1 hits
643 NME2 1 hits
644 NMT1 1 hits
645 NOD1 1 hits
646 NOD2 1 hits
647 NOS1 1 hits
648 NOS2A 1 hits
649 NOS3 1 hits
650 NOTCH1 1 hits
651 NOX4 1 hits
652 NOX5 1 hits
653 NPC1 1 hits
654 NPHS1 1 hits
655 NPPA 1 hits
656 NPPC 1 hits
657 NPY 1 hits
658 NPY5R 1 hits
659 NPY6R 1 hits
660 NR0B2 1 hits
661 NR1H2 1 hits
662 NR1H4 1 hits
663 NR2C2 1 hits
664 NR3C1 1 hits
665 NR3C2 1 hits
666 NR4A1 1 hits
667 NR4A3 1 hits
668 NR5A2 1 hits
669 NSF 1 hits
670 NT5C2 1 hits
671 NUCB2 1 hits
672 NUDT6 1 hits
673 OCLN 1 hits
674 ODC1 1 hits
675 OGT 1 hits
676 OLR1 1 hits
677 ONECUT1 1 hits
678 OPRD1 1 hits
679 OPRK1 1 hits
680 OPRM1 1 hits
681 OSBPL8 1 hits
682 OSM 1 hits
683 OXCT1 1 hits
684 P4HB 1 hits
685 PAH 1 hits
686 PAPPA 1 hits
687 PARD6A 1 hits
688 PARP1 1 hits
689 PAX4 1 hits
690 PAX6 1 hits
691 PC 1 hits
692 PCIF1 1 hits
693 PCK1 1 hits
694 PCK2 1 hits
695 PCNA 1 hits
696 PCNT 1 hits
697 PCSK1 1 hits
698 PCSK2 1 hits
699 PCSK9 1 hits
700 PDE3B 1 hits
701 PDE5A 1 hits
702 PDGFA 1 hits
703 PDGFRB 1 hits
704 PDHA1 1 hits
705 PDHB 1 hits
706 PDHX 1 hits
707 PDIA3 1 hits
708 PDIK1L 1 hits
709 PDK1 1 hits
710 PDK2 1 hits
711 PDK4 1 hits
712 PDLIM5 1 hits
713 PDPK1 1 hits
714 PDR 1 hits
715 PDX1 1 hits
716 PDXP 1 hits
717 PEA15 1 hits
718 PENK 1 hits
719 PF4V1 1 hits
720 PFKL 1 hits
721 PFKM 1 hits
722 PGF 1 hits
723 PGM1 1 hits
724 PGR 1 hits
725 PHF12 1 hits
726 PHKA1 1 hits
727 PI3 1 hits
728 PIK3C2A 1 hits
729 PIK3CA 1 hits
730 PIK3CB 1 hits
731 PIK3CG 1 hits
732 PIK3R1 1 hits
733 PIK3R2 1 hits
734 PIK3R3 1 hits
735 PIP 1 hits
736 PIP5K1A 1 hits
737 PKLR 1 hits
738 PKM2 1 hits
739 PKN1 1 hits
740 PKNOX1 1 hits
741 PLA2G1B 1 hits
742 PLA2G6 1 hits
743 PLA2G7 1 hits
744 PLAT 1 hits
745 PLCB1 1 hits
746 PLCG1 1 hits
747 PLIN 1 hits
748 PLN 1 hits
749 PLOD1 1 hits
750 PLTP 1 hits
751 PMCH 1 hits
752 PNLIP 1 hits
753 PNMT 1 hits
754 PNPLA2 1 hits
755 PNPLA3 1 hits
756 POMC 1 hits
757 PON1 1 hits
758 PPA1 1 hits
759 PPARA 1 hits
760 PPARD 1 hits
761 PPARG 1 hits
762 PPARGC1A 1 hits
763 PPARGC1B 1 hits
764 PPP1CA 1 hits
765 PPP1R12A 1 hits
766 PPP1R13B 1 hits
767 PPP1R3A 1 hits
768 PPP1R3C 1 hits
769 PPP2R3B 1 hits
770 PPP2R4 1 hits
771 PPY 1 hits
772 PREB 1 hits
773 PRKAA1 1 hits
774 PRKAA2 1 hits
775 PRKAR2A 1 hits
776 PRKCA 1 hits
777 PRKCB1 1 hits
778 PRKCD 1 hits
779 PRKCE 1 hits
780 PRKCZ 1 hits
781 PRKD1 1 hits
782 PRKG1 1 hits
783 PRL 1 hits
784 PRMT1 1 hits
785 PROX1 1 hits
786 PRPS1 1 hits
787 PSEN1 1 hits
788 PSEN2 1 hits
789 PSMD8 1 hits
790 PTBP1 1 hits
791 PTEN 1 hits
792 PTF1A 1 hits
793 PTGDS 1 hits
794 PTGS1 1 hits
795 PTGS2 1 hits
796 PTH 1 hits
797 PTK2 1 hits
798 PTK2B 1 hits
799 PTPN1 1 hits
800 PTPN2 1 hits
801 PTPN6 1 hits
802 PTPRA 1 hits
803 PTPRC 1 hits
804 PTPRF 1 hits
805 PTPRN 1 hits
806 PTPRN2 1 hits
807 PTPRR 1 hits
808 PTPRT 1 hits
809 PTPRU 1 hits
810 PTPRV 1 hits
811 PTRF 1 hits
812 PTTG1 1 hits
813 PWCR 1 hits
814 PYCARD 1 hits
815 PYGM 1 hits
816 PYY 1 hits
817 RAB1A 1 hits
818 RAB27A 1 hits
819 RAB2A 1 hits
820 RAB3A 1 hits
821 RAB3B 1 hits
822 RAB4A 1 hits
823 RAB6A 1 hits
824 RAC1 1 hits
825 RAF1 1 hits
826 RAG2 1 hits
827 RALBP1 1 hits
828 RAP1A 1 hits
829 RARRES2 1 hits
830 RASD2 1 hits
831 RASGRF1 1 hits
832 RB1 1 hits
833 RBM5 1 hits
834 RBP1 1 hits
835 RBP4 1 hits
836 REG1A 1 hits
837 REG3A 1 hits
838 REN 1 hits
839 RENBP 1 hits
840 RETN 1 hits
841 RETNLB 1 hits
842 RGS16 1 hits
843 RHBG 1 hits
844 RHOD 1 hits
845 RHOQ 1 hits
846 RNF123 1 hits
847 RNU105B 1 hits
848 RNU1A3 1 hits
849 ROCK1 1 hits
850 RORC 1 hits
851 RP9 1 hits
852 RPS27A 1 hits
853 RPS6 1 hits
854 RPS6KA1 1 hits
855 RPS6KB1 1 hits
856 RSPO1 1 hits
857 RYR2 1 hits
858 S100A12 1 hits
859 S100G 1 hits
860 SAA 1 hits
861 SAA2 1 hits
862 SAA3P 1 hits
863 SART3 1 hits
864 SAT1 1 hits
865 SCAF1 1 hits
866 SCARB1 1 hits
867 SCARNA14 1 hits
868 SCD 1 hits
869 SCGN 1 hits
870 SCN2A 1 hits
871 SDC1 1 hits
872 SDPR 1 hits
873 SELPLG 1 hits
874 SENP1 1 hits
875 SEPP1 1 hits
876 SERPINA1 1 hits
877 SERPINA12 1 hits
878 SERPINC1 1 hits
879 SERPIND1 1 hits
880 SERPINE1 1 hits
881 SERPINE2 1 hits
882 SERPINF1 1 hits
883 SETD2 1 hits
884 SFTPA1 1 hits
885 SFTPA2B 1 hits
886 SFTPB 1 hits
887 SGCB 1 hits
888 SGK1 1 hits
889 SGMS1 1 hits
890 SGMS2 1 hits
891 SH2B1 1 hits
892 SH2B2 1 hits
893 SHB 1 hits
894 SHBG 1 hits
895 SHC1 1 hits
896 SIRT1 1 hits
897 SIRT2 1 hits
898 SLC10A2 1 hits
899 SLC15A1 1 hits
900 SLC20A1 1 hits
901 SLC25A19 1 hits
902 SLC27A1 1 hits
903 SLC29A1 1 hits
904 SLC2A1 1 hits
905 SLC2A10 1 hits
906 SLC2A2 1 hits
907 SLC2A3 1 hits
908 SLC2A4 1 hits
909 SLC2A5 1 hits
910 SLC2A8 1 hits
911 SLC2A9 1 hits
912 SLC30A10 1 hits
913 SLC30A8 1 hits
914 SLC35B4 1 hits
915 SLC37A4 1 hits
916 SLC39A3 1 hits
917 SLC39A6 1 hits
918 SLC39A8 1 hits
919 SLC5A1 1 hits
920 SLC5A11 1 hits
921 SLC5A2 1 hits
922 SLC6A2 1 hits
923 SLC6A3 1 hits
924 SLC6A4 1 hits
925 SLC9A3 1 hits
926 SMAD2 1 hits
927 SMAD3 1 hits
928 SNAP23 1 hits
929 SNAPIN 1 hits
930 SNF1LK 1 hits
931 SNF1LK2 1 hits
932 SNORD46 1 hits
933 SNRPE 1 hits
934 SNTB1 1 hits
935 SNTG1 1 hits
936 SNW1 1 hits
937 SOCS1 1 hits
938 SOCS3 1 hits
939 SOD1 1 hits
940 SOD2 1 hits
941 SOD3 1 hits
942 SORBS1 1 hits
943 SORCS1 1 hits
944 SORD 1 hits
945 SOX4 1 hits
946 SOX9 1 hits
947 SP1 1 hits
948 SPAG8 1 hits
949 SPINK4 1 hits
950 SPP1 1 hits
951 SPTLC1 1 hits
952 SRC 1 hits
953 SREBF1 1 hits
954 SREBF2 1 hits
955 SRF 1 hits
956 SRPR 1 hits
957 SS18L1 1 hits
958 SST 1 hits
959 ST3GAL4 1 hits
960 ST6GAL1 1 hits
961 STAT1 1 hits
962 STAT3 1 hits
963 STAT5A 1 hits
964 STAT5B 1 hits
965 STC1 1 hits
966 STEAP4 1 hits
967 STH 1 hits
968 STK11 1 hits
969 STK38 1 hits
970 STK39 1 hits
971 STN 1 hits
972 STX1A 1 hits
973 STX4 1 hits
974 STXBP3 1 hits
975 STXBP5 1 hits
976 SUFU 1 hits
977 SUMO1 1 hits
978 SUMO4 1 hits
979 SYP 1 hits
980 SYT1 1 hits
981 SYT7 1 hits
982 SYT8 1 hits
983 TAC1 1 hits
984 TACR1 1 hits
985 TACSTD1 1 hits
986 TAS1R3 1 hits
987 TAT 1 hits
988 TBC1D1 1 hits
989 TBC1D4 1 hits
990 TBK1 1 hits
991 TBXAS1 1 hits
992 TCF3 1 hits
993 TCF4 1 hits
994 TCF7 1 hits
995 TCF7L1 1 hits
996 TCF7L2 1 hits
997 TERT 1 hits
998 TF 1 hits
999 TFAM 1 hits
1000 TFAP4 1 hits
1001 TFPI 1 hits
1002 TFRC 1 hits
1003 TG 1 hits
1004 TGFA 1 hits
1005 TGFB1 1 hits
1006 TGM2 1 hits
1007 THADA 1 hits
1008 THBD 1 hits
1009 THBS1 1 hits
1010 THM 1 hits
1011 THY1 1 hits
1012 TIMP1 1 hits
1013 TIMP3 1 hits
1014 TKT 1 hits
1015 TLR1 1 hits
1016 TLR2 1 hits
1017 TLR4 1 hits
1018 TLR5 1 hits
1019 TM7SF3 1 hits
1020 TMEM27 1 hits
1021 TNF 1 hits
1022 TNFRSF10A 1 hits
1023 TNFRSF11B 1 hits
1024 TNFRSF1A 1 hits
1025 TNFRSF25 1 hits
1026 TNFSF10 1 hits
1027 TNKS 1 hits
1028 TP53 1 hits
1029 TP73 1 hits
1030 TPH1 1 hits
1031 TPO 1 hits
1032 TRAF3 1 hits
1033 TRH 1 hits
1034 TRIB3 1 hits
1035 TRIM63 1 hits
1036 TRO 1 hits
1037 TRPM3 1 hits
1038 TRPM5 1 hits
1039 TRPV1 1 hits
1040 TSC2 1 hits
1041 TSHR 1 hits
1042 TTR 1 hits
1043 TXN 1 hits
1044 TXNIP 1 hits
1045 TYRP1 1 hits
1046 UBASH3B 1 hits
1047 UBE2I 1 hits
1048 UBL5 1 hits
1049 UCP1 1 hits
1050 UCP2 1 hits
1051 UCP3 1 hits
1052 UGCG 1 hits
1053 UNC13A 1 hits
1054 USF1 1 hits
1055 USP6 1 hits
1056 UTS2 1 hits
1057 VAMP2 1 hits
1058 VAMP8 1 hits
1059 VDR 1 hits
1060 VEGFA 1 hits
1061 VGF 1 hits
1062 VHL 1 hits
1063 VIM 1 hits
1064 VIP 1 hits
1065 VIPR1 1 hits
1066 VIPR2 1 hits
1067 VLDLR 1 hits
1068 VTN 1 hits
1069 VWF 1 hits
1070 VWS 1 hits
1071 WARS 1 hits
1072 WFS1 1 hits
1073 WNT2 1 hits
1074 WNT3A 1 hits
1075 WNT4 1 hits
1076 WRN 1 hits
1077 XBP1 1 hits
1078 XBPP1 1 hits
1079 ZDHHC17 1 hits
1080 ZFP36 1 hits
1081 ZNF24 1 hits

Related Sentences

# PMID Sentence
1 21744203 In addition, an unexpected role of the TRP channel TRPM3 as a gatekeeper of zinc, which is required for insulin storage, will be considered.
2 21821716 It has been previously reported that overexpression of activating transcription factor 6 (ATF6) reduces insulin gene expression in part via upregulation of small heterodimer partner.
3 21821716 In this study, we investigated whether ATF6 directly binds to the insulin gene promoter, and whether its direct binding represses insulin gene promoter activity.
4 21862013 To analyze the direct effects of paraoxonase-1 (PON1) on diabetes development and on ?-cell insulin release.
5 21862013 Incubation of ?-cells with PON1 also dose-dependently increased insulin secretion and its cellular content.
6 21862013 The addition of the PON1 carrier in the circulation - HDL, to ?TC3 cell line, had an additive effect on PON1-induced insulin secretion.
7 21862013 However, the PON1 free sulfhydryl group was shown to be essential for insulin release by PON1, as blocking the PON1 SH group, abolished PON1 stimulatory effect on insulin secretion.
8 21862613 Our previous studies demonstrated that the ceramides activate the Nod-like receptor family, pyrin domain containing 3 (Nlrp3) inflammasome to cause the generation of mature IL-1? and ablation of the Nlrp3 inflammasome in diet-induced obesity improves insulin signaling.
9 21878513 Here we study the role of BRS-3 in the regulation of glucose-stimulated insulin secretion (GSIS) and glucose homeostasis.
10 21896669 Obesity and type 2 diabetes are characterized by insulin resistance, and the common basis of these events is a chronic and systemic inflammatory process marked by the activation of the c-Jun N-terminal kinase (JNK) and inhibitor-?B kinase (IKK?)/nuclear factor-?B (NF?B) pathways, up-regulated cytokine synthesis, and endoplasmic reticulum dysfunction.
11 21907990 Insulin stimulated nitric oxide synthase (NOS) activity in human vein endothelial cells from G/G (n=4, p=0.03) but not the G/A (n=5, p=0.83) genotype.
12 21907990 Variability at the SH2B1 obesity locus is associated with MI in diabetic patients and with reduced insulin-stimulated NOS activity in human endothelial cells.
13 22114711 In skeletal muscle, the reduced GLUT4 expression in severe insulin resistance was associated with decreased ubiquitin-conjugating enzyme 9 (UBC9) expression while expression of GLUT1, TBC1D1 and AS160 was not significantly different among type 2 diabetic patients and matched controls.
14 22114711 Type 2 diabetic patients with severe insulin resistance have reduced expression of GLUT4 in skeletal muscle compared to patients treated with oral antidiabetic drugs alone.
15 21437903 Insulin treatment (10 mU/ml/30 min) increased the phosphorylation of the IR ?-subunit and Akt.
16 21782840 Insulin secretion from pancreatic ? cells is stimulated by glucagon-like peptide-1 (GLP-1), a blood glucose-lowering hormone that is released from enteroendocrine L cells of the distal intestine after the ingestion of a meal.
17 21782840 GLP-1 mimetics (e.g., Byetta) and GLP-1 analogs (e.g., Victoza) activate the ? cell GLP-1 receptor (GLP-1R), and these compounds stimulate insulin secretion while also lowering levels of blood glucose in patients diagnosed with type 2 diabetes mellitus (T2DM).
18 21782840 Investigational compounds that stimulate GLP-1 secretion also exist, and in this regard a noteworthy advance is the demonstration that small molecule GPR119 agonists (e.g., AR231453) stimulate L cell GLP-1 secretion while also directly stimulating ? cell insulin release.
19 21820006 Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two primary incretin hormones secreted from the intestine upon ingestion of glucose or nutrients to stimulate insulin secretion from pancreatic ? cells.
20 21820006 However, despites of plethora of rigorous studies, molecular mechanisms underlying how GIPR and GLP-1R activation leads to enhancement of glucose-dependent insulin secretion are still largely unknown.
21 21986512 Human placental lactogen (hPL) and prolactin increase maternal food intake by induction of central leptin resistance and promote maternal beta-cell expansion and insulin production to defend against the development of gestational diabetes mellitus.
22 22022575 GC treatment decreased lipogenesis but did not alter rates of ?-oxidation in Chub-S7 cells, whilst insulin increased lipogenesis in all adipocyte cell models.
23 22127749 In the K (ITT) > 1.56 group (n=81), hemoglobin A(1c) (HbA(1c)) significantly increased in both patients treated with insulin sensitizers (n=10) and patients not treated with insulin sensitizers (n=71).
24 22127804 The pancreatic effects of GLP-1 receptor agonists include glucose-lowering effects by stimulating insulin secretion and inhibiting glucagon release in a strictly glucose-dependent manner, increased beta-cell proliferation, and decreased beta-cell apoptosis.
25 21143387 In cardiomyocytes, CM from EAT of HFD-fed animals increased SMAD2-phosphorylation, a marker for activin A-signalling, decreased sarcoplasmic-endoplasmic reticulum calcium ATPase 2a expression, and reduced insulin-mediated phosphorylation of Akt-Ser473 versus CM from SAT and standard diet-fed animals.
26 21885868 Transfer experiments determined the role of hepatic tumor necrosis factor (TNF)/inducible nitric oxide synthase-producing dendritic cells (Tip-DCs) and adipose tissue macrophages (ATMs) in inflammation-induced insulin resistance, determined by homeostatic assessment of insulin resistance.
27 21896928 Sprague Dawley (SD) male rats received acute central (MBH) or systemic injections of vehicle, resveratrol, or SIRT1 inhibitor during basal pancreatic insulin clamp studies.
28 21911750 It is interesting that activation of AMPK by A769662 attenuated NF-?B-p65 DNA binding activity in obese T2D cells to levels measured in nonobese myocytes; however, this had no effect on insulin sensitivity of the cells.
29 21911750 Despite attenuation of NF-?B activity by AMPK, insulin resistance in obese T2D cells remained, suggesting factors in addition to inflammation may contribute to the insulin resistance phenotype in muscle cells.
30 21926268 This study aimed to investigate the roles of the multidomain adaptor protein APPL1 in modulating vascular actions of insulin in mice and in endothelial cells.
31 21926268 In endothelial cells, APPL1 potentiated insulin-stimulated Akt activation by competing with the Akt inhibitor Tribbles 3 (TRB3) and suppressed ERK1/2 signaling by altering the phosphorylation status of its upstream kinase Raf-1.
32 21926268 APPL1 plays a key role in coordinating the vasodilator and vasoconstrictor effects of insulin by modulating Akt-dependent NO production and ERK1/2-mediated ET-1 secretion in the endothelium.
33 21926281 Multivariable analyses suggested that age, BMI, and insulin sensitivity independently affect SHBG and testosterone levels and the risk of metabolic syndrome and its components.
34 21933986 In vivo studies showed insulin was able to suppress IRS-2 expression via activation of SREBP-1 in the liver, but this mechanism was not apparent in pancreatic islets from the same animal.
35 21933987 Tribbles 3 (TRB3) is associated with insulin resistance, an important trigger in the development of diabetic cardiomyopathy (DCM).
36 21940782 FoxO6 integrates insulin signaling to hepatic gluconeogenesis.
37 21940782 Insulin inhibits FoxO6 activity via a distinct mechanism by inducing its phosphorylation and disabling its transcriptional activity, without altering its subcellular distribution in hepatocytes.
38 21940782 Our data uncover a FoxO6-dependent pathway by which the liver orchestrates insulin regulation of gluconeogenesis, providing the proof-of-concept that selective FoxO6 inhibition is beneficial for curbing excessive hepatic glucose production and improving glycemic control in diabetes.
39 21958333 The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) stimulate glucose-induced insulin secretion; however, in patients with type 2 diabetes, the incretin system is impaired by loss of the insulinotropic effects of GIP as well as a possible reduction in secretion of GLP-1.
40 21958333 Both the GPCR agonist AR231453 and the novel bile acid mimetic INT-777 have been shown to stimulate GLP-1 release, leading to increased insulin secretion and improved glucose tolerance in mice.
41 21750265 Even in the presence of IBMX or GLP-1, their insulin release did not significantly change despite further enhanced cAMP accumulation in both cases.
42 21849270 AhR signaling also affects molecular clock genes to influence glucose metabolism.Objective: We investigated mechanisms by which AhR activation affects glucose metabolism.Methods: Glucose tolerance, insulin resistance, and expression of peroxisome proliferator-activated receptor-? (PPAR-?) and genes affecting glucose metabolism or fatty acid oxidation and clock gene rhythms were investigated in wild-type (WT) and AhR-deficient [knockout (KO)] mice.
43 21946517 We have recently shown that miR-33 regulates cholesterol efflux and high-density lipoprotein (HDL) formation, as well as fatty acid oxidation and insulin signaling.
44 22065737 The p70 ribosomal protein S6 kinase 1 (S6K1) plays a key role in cell growth and proliferation by regulating insulin sensitivity, metabolism, protein synthesis, and cell cycle.
45 21801810 Our data suggest that in 3T3-L1 adipocytes NPY inhibits insulin-stimulated glucose uptake in a GLUT4-dependent manner.
46 21801810 This study provides evidence that NPY impairs the insulin sensitivity of adipocytes and suggests that the Y1 receptor could be a potential therapeutic target for type 2 diabetes.
47 21827825 Insulin induced Wnt3a, Wnt4 and Brachyury expression in a temporal- and stage-specific pattern.
48 21827825 Only blastocysts cultured with insulin reached the Wnt3a, Wnt4 and Brachyury expression levels of stage 2 in vivo blastocysts, indicating that insulin is required for Wnt3a, Wnt4 and Brachyury expression during gastrulation.
49 21827825 Blastocysts grown in diabetic rabbits are retarded in development, a finding which supports our current results that insulin is highly likely required for early mesoderm formation in rabbit blastocysts by inducing a distinct spatiotemporal expression profile of Wnt3a, Wnt4 and Brachyury.
50 21871056 Intensive insulin therapy resulted in a significant decrease of sRAGE and thrombomodulin at Day 7, in diabetic but not in non-diabetic patients.
51 21906675 Recently it has been found that PRAS40 is regulated by its upstream phosphatidylinositol 3-kinase/Akt (PI3K/Akt) which is activated by many tyrosine kinase receptors growth factors including insulin-like growth factor 1.
52 21914810 In 293E, insulin increased the amount of mTORC1 retrieved by the transiently expressed nonphosphorylatable 4E-BP[5A] to an extent that varied inversely with the amount of PRAS40 bound to mTORC1.
53 21914810 RNAi depletion of PRAS40 enhanced 4E-BP[5A] binding to ?70% the extent of maximal insulin, and PRAS40 RNAi and insulin together did not increase 4E-BP[5A] binding beyond insulin alone, suggesting that removal of PRAS40 from mTORC1 is the predominant mechanism of an insulin-induced increase in substrate access.
54 21914810 In the presence of Rheb and insulin, PRAS40 release is abolished by Akt inhibition without diminishing mTORC1 signaling.
55 21926342 In GK (vs. age-matched control) aortas, various insulin-stimulated levels [nitric oxide production and the phosphorylations of eNOS at Ser(1177), of Akt at Thr(308), of phosphoinositide-dependent kinase-1 (PDK1) at Ser(241), of Src at Tyr(416), and of Pyk2 at Tyr(579)] were all significantly decreased and unaffected by either Src inhibitor (PP2) or Pyk2 inhibitor (AG17), while the insulin-stimulated levels of insulin receptor substrate (IRS)-1 phosphorylation at Ser(307), total-eNOS, and total-Akt were significantly increased.
56 21645024 Objective? Retinol-binding protein 4 (RBP4), produced by adipocytes and hepatocytes, contributes to an unfavourable lipid profile and insulin resistance, which can contribute to the development of coronary artery disease (CAD).
57 21679181 The levels of SHBG were associated negatively with the risk of T2D, obesity and insulin resistance in both men and women.
58 21711374 Insulin and glucose were negatively associated with SHBG levels, as well as IGF-1 and IGF-BP3, while no associations were found with free thyroid hormone status.
59 21726266 Conclusions? Multiple endocrine neoplasia type 1 patients had decreased insulin sensitivity and higher prevalence of impaired fasting glucose compared with controls, which was unrelated to MEN1 manifestations.
60 21916833 Leptin secretion from white adipocytes curbs appetite to limit dietary nutrient intake and adipocyte TAG storage and, potentially, GSIS, thereby curtailing insulin-dependent TAG storage.
61 22081023 We show that Met is essential for an optimal hepatic insulin response by directly engaging INSR to form a Met-INSR hybrid complex, which culminates in a robust signal output.
62 22147092 Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD).
63 4700328 Those patients requiring the largest insulin increment for the control of their diabetes in the pregnancy have placental lactogen levels in the higher range.
64 164620 The endocrine system plays a paramount role in glucokinase adaptation, since insulin is essential for glucose-dependent glucokinase induction and, on the other hand, glucagon, catecholamines and cyclic AMP prevent the induction.
65 166896 Glutathione-insulin-transhydrogenase is suggested by the appearance of a component that has the same elution volume as the A chain, but the inhibitory effects of trasylol on insulin degradation, as well as qualitative and quantitative similarities with insulin proteases, suggest that a proteolytic similiarities with insulin proteases, suggest that a proteolytic mechanism is involved.
66 237762 The triamcinolone effect on acetyl-CoA carboxylase activity appeared to be dependent on the coincident hyperinsulinemia since it was not obtained in alloxan-diabetic rats, whereas the alanine-aminotransferase-inducing effect of this hormone was additive to that of insulin deficiency.
67 168109 Although acute insulin deficiency in intact rats produced the previously described increase in protein synthetic activity of free hepatic ribosomes and decrease in activity of hepatic bound ribosomes, these changes did not occur in Hx rats, even when Hx rats received replacement doses of thyroxine, ACTH, and growth hormone.
68 1159060 In three maturity onset diabetics, somatostatin infusion abolished the insulin rise induced by breakfast and oral glucose, and in 2 of them, inhibited the basal insulin secretion by 50% seen during control studies.
69 53167 Accumulation of acetylcholinesterase (AChE) and choline acetylase (ChAc) activities proximal to a tie placed on the sciatic nerve was measured in control, untreated diabetic, and insulin-treated diabetic rats.
70 171190 With the perfused pancreas, somatostatin caused 32 per cent inhibition of glucose-mediated insulin release and inhibited arginine-induced glucagon release by 72 per cent.
71 1184738 The role of insulin in the regulation of human adipose tissue lipoprotein lipase was evaluated.
72 1184738 In contrast, the diabetic patients with low insulin responses, failed to increase lipoprotein lipase activity with feeding.
73 1184738 Thus, insulin appears to be important in the regulation of human adipose tissue lipoprotein lipase activity.
74 1186499 The effect of glucagon suppression by somatostatin upon endogenous hyperglycemia was studied in three forms of experimental insulin deficiency in dogs: alloxan diabetes, total pancreatectomy, and diazoxide administration.
75 1215908 Albumin and plasma protein almost completely prevent insulin adsorption.
76 1227847 Concentrations of immunoreactive insulin activity (IRI) and proinsulin activity (IRP), blood glucose, free fatty acids (FFA), glycerol, cholesterol, triglycerides were analyzed in 140 subjects suspect of protodiabetes and 50 healthy persons before, during and after a glucose infusion test (GIT).
77 791728 Finally, in insulin-dependant diabetics, somatostatin infusion reduces plasma glucagon concentration and blood glucose and prevents the development of ketosis after withdrawal of insulin therapy.
78 176403 Alteration of growth of dimethylbenz[a]anthracene-induced mammary tumors was caused by removal of estrogen (ovariectomy), or insulin (diabetes), or by inhibition of prolactin secretin (treatment with an ergoline derivative).
79 814025 The effects of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, substance P, somatostatin, and a partially purified hypothalamic extract on insulin secretion were tested both in vitro and in vivo.
80 814025 Only somatostatin and the hypothalamic extract affected insulin secretion.
81 814025 In vitro, somatostatin decreased glucose-stimulated insulin secretion by isolated islets and in vivo significantly reduced the rate of insulin output into the portal vein.
82 1254110 The nonsuppressible insulin-like (NSILA-s) and somatomedin-like activities of the serum were not elevated, and the tumor did not release insulin-like activity on incubation nor did it contain somatostatin.
83 1259204 The assays done by the Eli Lilly Research Department revealed no in vitro effect of insulin on the CAMP and GMP level of mast cells as occurs in liver cells.
84 5326 Glucagon, insulin, and gastrin levels were suppressed by somatostatin while calcium infusion caused a paradoxical increase.
85 61140 The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously.
86 960073 HLA-A and B antigens were determined in 112 patients with insulin-dependent juvenile onset diabetes mellitus, who could be subdivided into "non" and "high responder" to insulin.
87 185113 In the control and the insulin resistant subjects the quantity of LDL apoprotein catabolised per day agreed closely with the amount derived from VLDL B-apoprotein conversion, suggesting that VLDL-B-apoprotein serves as the main source of LDL apoprotein.
88 974179 Pyruvate kinase activity was decreased under diabetes, and insulin injections produced further decrease of the enzyme activity in diabetic rats.
89 976635 The study investigated the respective influences of nicotinic acid and somatostatin on plasma concentrations of blood glucose, free fatty acids, glucagon, growth hormone and cortisol in insulin-dependent diabetic subjects.
90 976937 This PDR lasted 3 to 4 hours and was evaluated by glucemia and glucosuria determination and by the appearance of an insulin antagonist, alpha2-glycoprotein STH-dependent, called alpha2-inhibitor, which inhibits glucose uptake by isolated tissues.
91 186865 There are several causes for hyperlipemia in the diabetic: (a) an increase in hepatic synthesis of prebetalipoproteins, and (b) reduced elimination of prebetalipoproteins and chylomicrons from the bloodstream, due to diminished activity of lipoprotein lipase in insulin deficiency.
92 992197 Adipose tissue lipoprotein lipase activity (LPLA) and cellularity have been studied in controls, in diabetic or non-diabetic obese subjects and in insulin dependent diabetic patients.
93 1033640 The inhibitory effect of somatostatin on the secretion of glucagon permits the examination of the effect of glucagon on some metabolic parameters in the insulin-dependent diabetic patient.
94 1033640 The results obtained in 5 insulin-dependent diabetics and in 4 pancreatectomized patients revealed an inhibitory effect of somatostatin on blood glucose in the juvenile-type diabetics, but failed to show this influence of somatostatin in the pancreatectomized patients.
95 211005 The presence of somatostatin within the pancreatic D cells raises the possibility that it may function as a local regulator of insulin and glucagon release.
96 187516 Insulin treatment of ketotic diabetes resulted in a rapid increase in the activity of LPL and decrease in serum triglycerdie level, whereas sulfonylurea treatment of non-insulin-requiring diabetics did not significantly influence the enzyme activity.
97 187516 The activity of LPL was correlated to basal plasma insulin concen tration in the insulin-deficient diabetes r = +0.34) but not in patients with maturity-onset-type diabetes.
98 188551 Prolactin binding to both tumor and liver was significantly reduced in diabetic rats, suggesting that insulin may play an important role in controlling tissue sensitivity to prolactin.
99 188551 Prolactin binding to both tumor and liver was significantly reduced in diabetic rats, suggesting that insulin may play an important role in controlling tissue sensitivity to prolactin.
100 189835 The effect of diabetes and insulin on the activities of both prolyl hydroxylase (trivial name; proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) and lysyl hydroxylase (trivial name; lysine,2-oxoglutarate dioxygenase, EC 1.14.11.4) in isolated rat renal glomeruli was determined.
101 264686 We conclude that somatostatin caused only transient hypoglycemia in normal subjects and that hyperglycemia eventually developes as a consequence of insulin deficiency.
102 140046 The binding of labeled insulin was inhibited by low concentrations of unlabeled insulin and by high concentrations of proinsulin, whereas it was unaffected by the presence of glucagon, gastrin, prolactin, ACTH, or growth hormone in microgram amounts.
103 323091 In in-vitro experiments with isolated pancreatic islets, GIP significantly augmented insulin release induced by either 8.3 mM or 16.7 mM glucose, whereas the augmentation of glucagon release was observed at 3.3 mM, 8.3 MM, and 16.7 mM glucose concentrations.
104 323091 Three peptides, consisting of 1-28, 22-43, and 15-43 amino acids of GIP, failed to potentiate insulin and glucagon secretion.
105 870515 To determine whether cyclic somatostatin (GH-RIH) interferes with glucose utilization and gluconeogenesis we studied levels of blood glucose (BG), immunoreactive insulin (IRI), immunoreactive glucagon (IRG) and of human growth hormone (GH) after iv glucose (330 mg/kg) and iv arginine (0.5 g/kg) in healthy subjects (n=8) and in maturity onset diabetics (n=8; fasting BG less than 200 mg/dl) both in the presence and in the absence of GH-RIH (500 microng/h iv).
106 326606 It is suggested that somatostatin plays an important role in the regulation of insulin release in the physiologic range of glucose concentration.
107 301801 The results suggest that von Willebrand factor activity is suppressed coincident with the rise of glucose and insulin and provide further evidence of hormonal and metabolic control of levels of von Willebrand factor activity.
108 908462 Infusion of somatostatin along with insulin prevented the effects of diazoxide on plasma glucose and glucose production.
109 908478 A longer acting and more selective somatostatin preparation may prove useful as an adjunct to insulin in the management of diabetes.
110 917016 Determinations of the components of the kinin system indicate that the kininogenase activity is increased, and both the kininogen and kininase content are in turn decreased in the plasma of insulin-treated animals.
111 591612 The failure of apomorphine to affect glucagon secretion, despite a substantial effect on growth hormone and prolactin, was also observed in insulin-dependent diabetics known to exhibit A-cell hyperresponsiveness to various stimuli.
112 415444 Treatment with insulin led to lowering of serum GOT, GPT, and ceruloplasmin while serum alkaline phosphatase remained low.
113 340309 In severely diabetic mice, islets presented a reduced proportion of insulin containing cells but increased glucagon-, somatostatin-, and pancreatic polypeptide (PP)-containing cells, as compared with islets of control (+/+) mice.
114 621574 In the absence of insulin, fasting alone was able to reduce the serum alkaline phosphatase of diabetic rats to control values.
115 205552 In the high-dose insulin-treated diabetic rats, glucagon binding and basal and glucagon-stimulated adenylate cyclase activity were normalized to control values, whereas low-dose insulin treatment resulted in changes intermediate between control and untreated diabetic rats.
116 416984 The quantity of insular amyloid correlated significantly with glucose clearance in intravenous glucose tolerance tests and with serum glucose, triglycerides, immunoreactive insulin, and prebetallipoprotein measured after an overnight fast.
117 640235 In the normals, somatostatin suppressed plasma growth hormone, glucagon, and insulin but increased plasma glucose.
118 640235 The elevated plasma glucose levels in normals must be due to the suppressive effects of somatostatin on insulin secretion.
119 661568 Somatostatin inhibited glucose-stimulated insulin release and reduced plasma glucagon by 50%--65%.
120 98419 Alrestatin, a lens aldose reductase inhibitor, decreased i.v. arginine-induced glucagon levels and augmented arginine-stimulated insulin release in the ether anesthetized rat.
121 81157 IV insulin decreased urinary excretion of beta-2-microglobulin and increased albumin excretion (2 p less than 0.05).
122 81157 The albumin excretion induced by insulin is most likely due to increased amounts of filtered albumin, the mechanism of which remains unexplained.
123 151683 Earlier work demonstrated that the activity of liver phosphofructokinase (PFK-L2) and immunoreactive PFK-L2 were decreased in diabetic rats and increased to normal or super-normal amounts following insulin treatment (Dunaway, G.A., and Weber, G., (1974) Arch.
124 698217 Other lectins (wheat germ agglutinin, Dolichos) and enzymes (alpha-L-fucosidase, beta-N-acetyl-hexosaminidase and neuraminidase) are without effect on insulin binding.
125 700257 The results indicate that a preparation with a pattern of hormone suppression like that of somatostatin will not be useful in the control of maturity-onset diabetes, because it suppresses insulin and elevates the blood glucose concentration.
126 152519 Insulin treatment of non-diabetic female rats resulted in slight decreases in aminopyrine N-demethylase and aniline hydroxylase activities, but no changes in cytochrome P-450 content.
127 153061 Insulin treatment of diabetic animals returned the altered AHH activity to control values in both sexes of rats. 2.
128 282608 We have studied the effects of alloxan-induced diabetes and subsequent insulin replacement on albumin and total hepatic protein synthesis.
129 721253 The liver insulinase activity of diabetic dogs after acetazolamide administration was also studied to evaluate the role of this enzyme for the destruction of exogenous insulin.
130 729537 Insulin appeared to have a specific effect on the activities of glucokinase, ATP-citrate lyase, malic enzyme, and glucose-6-P-dehydrogenase.
131 373769 It is suggested that rates of oxidation of lipid fuels may be a major determinant of the activity of pyruvate dehydrogenase in tissues in relation to the actions of insulin and lipolytic hormones and the effects of diabetes and starvation.
132 400725 Insulin treatment did not affect the GIP, glucagon-like immunoreactivity, or IRG responses to oral glucose.
133 759824 The role of insulin in the regulation of LPL has been well documented.
134 84999 DAMME and other substances with opiate-like activity, such as morphine and beta-endorphin, affect carbohydrate metabolism and insulin secretion.
135 220534 The beta-cell localization of human pancreatic kallikrein, an endopeptidase that, in concert with carboxypeptidase B, converts bovine proinsulin to a polypeptide with the electrophoretic mobility of insulin, suggests that pancreatic kallikrein may be involved in the physiologic activation of proinsulin.
136 374172 Freshly isolated islets are relatively insensitive to somatostatin, requiring 100 ng/ml to suppress partially the glucose-induced insulin secretion.
137 437377 Cytochrome b5 levels were elevated in the face of decreased fatty acid desaturation and returned to normal after 48 h of insulin treatment; 2 U of regular insulin every 6 h for 24 h repaired the fatty acid desaturation defect, while 0.5 U failed to correct the defect.
138 437377 This, together with the fact that delta 6 desaturase activity in diabetes (64% of control) is altered less than is delta 9 desaturase activity (22% of control), indicates that delta 6 desaturase enzyme activity is less responsive to insulin than is delta 9 desaturase enzyme activity.
139 446917 The addition of insulin (10(-7) M and 10(-6) M) had no significant effect on somatostatin and glucagon release.
140 456774 Although all groups showed an increase of plasma insulin after oral glucose, both the diabetic and nondiabetic hypertriglyceridaemics had impaired activities of lipoprotein lipase in adipose tissue compared to the obese normals (p less than 0.02, p less than 0.03, respectively).
141 456774 A course of insulin therapy (20 u.o.d.) for one week increased the activity of lipoprotein lipase extracted from adipose tissue, lowered plasma triglycerides and improved triglyceride clearance from plasma in a group of diabetics with hypertriglyceridaemia (mean plasma triglyceride 8.7 mmol/l).
142 457845 An insulin infusion test was administered to test the hypothesis that insulin suppresses GIP secretion.
143 457845 These results do not support a direct role for insulin in suppressing GIP in normal or diabetic subjects.
144 157804 Since we had earlier shown that insulin action on transport in these tumor cells were directed towards the A system, we examined the effects of insulin, estradiol, and their combination in vitro on proline and leucine transport.
145 223535 Growth hormone (hGH) responsiveness to exercise and somatomedin C (SmC) activity were measured in ten children with insulin-deficient diabetes mellitus.
146 224797 Prolactin release could not be stimulated by TRH, levodopa, metoclopramide, chlorpromazine and insulin hypoglycemia.
147 225168 In insulinoma, both insulin and C-peptide increased and PLC occupied 5.48 and 5.96%, respectively.
148 489974 Administration of insulin to diabetic mice is associated with a partial reversal of the decreased ability of their lymphoid cells to generate ESP.
149 510813 Fat feeding stimulated the release of gastric inhibitory polypeptide (GIP) without concomitant insulin secretion.
150 400579 Since pyruvate kinase activity in diabetic dogs without endotoxin treatment was not affected, these findings suggest that the stimulatory effect of endotoxin on pyruvate kinase activity in diabetic dogs may be associated with insulin deficiency and/or high ambient blood glucose level.
151 6444670 In contrast, adrenalectomy or insulin administration prevented the diabetes and elevations of circulating DBH.
152 6986299 The infusion of insulin alone (in the presence of elevated glucose levels) or together with glucose significantly suppressed the IR-GIP rise after fat ingestion, but it did not alter the GIP response to oral glucose.
153 6987118 Effects of arginine and such pancreatic hormones as insulin and pancreatic polypeptide on gastric somatostatin release from the isolated perfused rat stomach were studied.
154 6987118 Both insulin and pancreatic polypeptide (10(-10), 10(-9), and 10(-8) M) caused a significant decrease in gastric somatostatin secretion.
155 6987118 Insulin (10(-10) M), furthermore, inhibited the glucagon (5 x 10(-8) M)-induced somatostatin response.
156 6987123 The infusion of 19 mM arginine significantly augmented secretion of somatostatin and glucagon and attenuated insulin secretion in 48-h fasted rats.
157 6988274 All showed antibody binding of insulin, 29 binding of proinsulin, 29 binding of pancreatic polypeptide, two binding of glucagon but none of the sera bound vasoactive intestinal peptide or somatostatin.
158 6989262 Calcification of cartilage and osteogenesis were reduced by more than 50% in diabetic rats and corrected by insulin as measured by alkaline phosphatase activity and 45Ca incorporation.
159 6989547 After 6 wk renin and aldosterone responses were again determined, as were oral glucose tolerance and serum potassium and serum insulin levels.
160 6104595 These results suggest that an abrupt deprivation of insulin from islets results in an elevation of pancreatic somatostatin concentration, and that glucagon in the pancreas plays a minor role in determining pancreatic somatostatin concentration in rats with insulin-deprived diabetes of short duration.
161 6155299 The ability to induce hyperglycemia by an insulin antiserum can be predicted by the titer of ABR measured.
162 6445842 Insulin treatment within 10 h of the SZ injection prevented the increase of ODC activity; however, insulin given after enzyme activity had increased did not restore ODC activity to control levels.
163 6991329 However, omission of calcium from the adipocyte incubation media significantly lowered the insulin stimulation by 24% while basal levels were not significantly affected.
164 6991335 In these studies, we show that lysosomal degradation of internalized receptor-bound insulin is not necessary for insulin to cause short-term biologic effects in the adipocyte.
165 6995476 Glucose-dependent insulin-releasing peptide or gastric inhibitory polypeptide (GIP) is released into the circulation after ingestion of a mixed meal and is thought to enhance glucose-induced insulin release.
166 6997022 In diabetic patients plasma levels of pancreatic polypeptide (PP) increased four fold after intramuscular injection of secretin (50 CHRU, Eisai Co.) in spite of the lack of response of plasma insulin, plasma glucagon and blood glucose levels.
167 6998798 Contrary to expectation insulin decreased urinary albumin excretion (from 418 to 312 micrograms/min, 27 per cent) in these patients.
168 6998809 Beta-2-microglobulin excretion decreased but this difference was not significant. -- It is concluded that the rise in heart rate and plasma noradrenaline, and the increase in urinary albumin excretion, after insulin, are unrelated to changes in blood glucose concentration.
169 7418953 The serum activities of two lysosomal enzymes, beta-N-acetylglucosaminidase (EC 3.2.1.30, NAG) and beta-glucuronidase (EC 3.2.1.31, GLU), were determined in 41 insulin-dependent diabetics, 27 age-matched non-diabetic first-degree relatives of the diabetics and 103 age-matched non-diabetic blood-donors.
170 6108269 The pancreatic somatostatin content increased in proportion to the dose of STZ (I, 189 +/- 31; II, 222 +/- 20, III, 343 +/- 4; IV, 515 +/- 36 ng/g wet wt), while graded reductions of insulin content were observed.
171 6108269 Pancreatic somatostatin release increased during arginine infusion (19.2 mM) dose dependently, (I, 543 +/- 36; II, 946 +/- 64; III, 1229 +/- 55; IV, 2186 +/- 150 pg/15 min), and it correlated with the graded decreases of insulin release.
172 6108269 These results indicate that pancreatic somatostatin content and release increased in STZ-diabetic rats in proportion to the degree of insulin deficiency.
173 6108274 Studies in vitro using the isolated perfused rat pancreas revealed a significant increase of somatostatin release from the diabetic pancreas, with a marked reduction of insulin release and almost normal glucagon release.
174 6108275 In spite of the marked, fifteenfold stimulation of somatostatin release (1.5 x 10-10 M in the perfusate effluent) by glucose, the concentration of somatostatin was insufficient to significantly alter glucose-stimulated insulin release in the isolated perfused rat pancreas.
175 6160072 To assess the effects of endogenous somatostatin on pancreatic islet A- and B-cell function, isolated rat islets were incubated in antisomatostatin gamma-globulin to bind endogenously released somatostatin, and the insulin and glucagon secretion of these islets was compared with that of islets incubated in gamma-globulin isolated from nonimmune serum.
176 6448739 In rats treated with insulin, blood glucose levels and glycosuria decreased, and serum somatomedin A returned to 108.3% +/- 11.7% of the initial values by the sixth day of treatment.
177 6777219 A series of synthetic peptides corresponding to the amino-terminal sequence of human growth hormone (hGH) has been studied for insulin-potentiating effects using three different bioassay systems: (1) intravenous insulin tolerance tests, (2) insulin binding to specific receptors of hepatic plasma membranes and isolated hepatocytes, and (3) modulation of insulin-dependent glycogen synthase and glycogen phosphorylase in muscle and adipose tissue.
178 6108887 Infusion of somatostatin together with glucagon suppressed the glucagon-induced increase in insulin and greatly augmented the increase in blood glucose.
179 6110570 The present study was undertaken to reevaluate the influence of somatostatin on platelet function in insulin-dependent diabetics and in normal subjects.
180 6257880 When KK mice had been injected with IAP, they responded to epinephrine and isoproterenol more readily than did ddY mice in increasing plasma insulin and glycerol.
181 7013838 In the control of insulin dependent diabetes in a remission, hemoglobin A1c allowed assessment of the regulation of carbohydrate metabolism after suppression of insulin therapy.
182 6110595 A possible deficiency of somatostatin, one of the factors controlling insulin release, has only recently been considered.
183 6110596 Binding of glucagon and insulin to the L fraction was very low while, in contrast, somatostatin binding was substantial and linear with lymphocyte number.
184 6110597 Perfusion with medium containing 1 microM muscimol inhibited glucose-stimulated somatostatin release by 38%, whereas the course of glucose-stimulated insulin release was unaffected.
185 6110603 High plasma levels of free fatty acids (FFA) stimulate the secretion of splanchnic somatostatin, and both are elevated in insulin deficiency.
186 6110604 Addition of 1 microgram/ml porcine insulin to the perfusion medium did not modify the alterations in somatostatin and glucagon responses to arginine.
187 7009280 The intragastric administration of naloxone (4 mg), a specific opiate receptor antagonist, reduced the insulin response and augmented the glucagon response to the digested gluten test meal, whereas the response of both hormones to the undigested gluten meal was not affected by naloxone.
188 6111219 The location of somatostatin in pancreatic islet D cells suggests that it may act as a local regulator of insulin and glucagon secretion.
189 6111928 These studies assessed the ability of des-Asn5-[D-Trp8-D-Ser13]-somatostatin (d-ATS-SS) to selectively inhibit insulin release and produce a hyperglycemia sufficient to compensate for the original impairment. d-ATS-SS at 0.017 micrograms/min inhibited basal insulin output (delta = -38 +/- 6%, P less than 0.005) and increased basal pancreatic glucagon output (delta - +21 +/- 6%, P less than 0.05, n = 5). d-ATS-SS at 0.17 micrograms/min markedly inhibited insulin output (delta = -84 +/- 4%, P less than 0.0005) and slightly inhibited glucagon output (delta = -14 +/- 6%, P less than 0.05, n = 5). d-ATS-SS at 0.055 micrograms/min decreased basal and stimulated insulin release but not basal nor stimulated glucagon release.
190 6164586 Insulin release was stimulated 50-fold and somatostatin (SRIF) secretion twofold when the glucose concentration was increased from 100 mg/dl to 300 mg/dl.
191 6784807 Somatostatin was infused during the experiment to suppress endogenous insulin secretin.
192 6114914 During the 3 hour period following glucose loading plasma concentrations of glucagon and growth hormone were diminished by somatostatin, as were the rise in blood glucose and insulin requirement (4.0 +/- 1.2 U) when compared with the control study (11.3 +/- 1.5 U; p less than 0.01).
193 6788617 Using a high resolution automated chromatographic method, the levels of the different minor haemoglobins Hb A1a, A1b, and A1c were measured in 20 healthy controls, in 20 patients with chronic renal failure, in 20 uraemic patients on intermittent haemodialysis, and in 20 insulin-dependent diabetic patients.
194 7018971 Addition of insulin and amino acids had no effect; however, 50% rat serum increased ODC activity four- to seven-fold after the initial decrease.
195 7018971 These findings suggest that insulin modulates the synthesis of ODC via production of a second circulating factor, the activity of which is diminished in serum of diabetic rats.
196 7021386 Both in starved and unstarved groups of normal mice, pyruvate dehydrogenase complex activity increased equally by insulin administration.
197 7022106 In obesity, IDDM and NIDDM there were no change in insulin sensitivity or in insulin responsiveness.
198 6115786 The effects of somatostatin on spontaneous hyperglycemia, plasma growth hormone, and IRG after withdrawal of insulin treatment was studied in 4 patients.
199 6115786 Somatostatin blunted both the hyperglycemic and paradoxical IRG responses to the glucose challenge, and reduced the spontaneous rise of blood glucose that occurred after insulin withdrawal.
200 6271530 The addition of TSH and insulin to the culture medium significantly increased the rate of thyroglobulin hydrolysis in glands of diabetic mice over that resulting from the addition of dibutyryl cAMP alone.
201 6271617 The possible physiologic significance of these results is discussed, emphasizing the idea of dual control of glycolysis and insulin release by glucokinase and hexokinase.
202 7026548 When glucagon or insulin was given to pancreatectomized rats, dietary induction of ODC was restored to a level found in normal rats.
203 7026548 These results suggest that increased influx of amino acids into liver is a critical factor for dietary induction of ODC and that both glucagon and insulin play a role in stimulating amino acid influx.
204 6213639 To test the effectiveness of SOD against streptozotocin in vitro, canine islets were incubated 10 min with or without streptozotocin (0.1 mg/ml) with 4 mM glucose; their functional integrity was tested subsequently as the insulin secretory response to 28 mM glucose.
205 6286296 Case 1 has remained consistently insulin-dependent and associated with positive islet cell antibody, gastric parietal cell antibody, thyroglobulin hemoagglutinating antibody and thyroidal microsomal hemoagglutinating antibody.
206 7049672 The current study was undertaken to determine if superoxide dismutase (SOD), the enzyme that converts superoxide to hydrogen peroxide, is altered in the mucosa of the alimentary tract and renal cortex of the diabetic rat, and if so, whether SOD responds to insulin treatment.
207 7049672 The level of Mn-SOD was not affected by diabetes or insulin treatment, but the cyanide-sensitive [copper- and zinc containing SOD (Cu-Zn SOD] SOD was depressed in the small intestine and colon of diabetic rats.
208 7049672 Insulin treatment restored total and Cu-Zn SOD activity in the small intestine to normal and increased Cu-Zn SOD activity in the colon to normal.
209 7050060 HADH activity was increased in the normal and diabetic insulin-treated trained groups, but because of its already high activity in the diabetic diaphragm, it did not require an adaptation.
210 7051007 In this study, the effects of glucose and insulin on the contractile response of cloned homogeneous cultures of rat glomerular mesangial cells to angiotensin II were examined.
211 7051007 From these data, it appears that insulin may be required for the contractile response of mesangial cells to angiotensin II.
212 6295856 In search of possible factors which impair insulin release, we have investigated the effect of naloxone, a specific opiate receptor blocker, on insulin responses to glucose in subjects with non-insulin-dependent diabetes, as well as in normal subjects.
213 6759233 The effects of insulin were not associated with any significant changes in glucagon or somatostatin levels in the culture media.
214 6760859 A radioimmunoassay specific for liver pyruvate kinase was used to determine the mechanism(s) involved in the insulin stimulation of this enzyme activity in chronically diabetic rats.
215 6760859 Liver pyruvate kinase activity, which is depressed in diabetes, did not respond to insulin until 36 h of treatment, with a more substantial increase occurring by 60 h.
216 6760859 These results demonstrate that a dual mechanism, i.e. an increase in both the quantity and specific activity of the enzyme, regulates the insulin-mediated stimulation of liver pyruvate kinase in the diabetic rat.
217 6761438 Chronic treatment with insulin significantly depressed by 48% intravascular phagocytosis of colloidal carbon administered IV at a dose of 8 mg/100 g, while glucagon and somatostatin stimulated macrophage endocytic function by 32% and 26%, respectively, compared to the control value.
218 7151653 In 102 insulin-dependent diabetic patients without retinopathy and with visual acuity 20/20, the Farnsworth-Munsell 100-Hue test was performed, and glycosylated hemoglobin (GlHb) levels were determined.
219 7152136 In the alloxan-diabetic dogs, treated with insulin alone, blood glucose, ketone body concentrations, and plasma somatostatin and glucagon levels were elevated.
220 7159398 In perfused hearts of alloxan-diabetic rats, insulin induced a modest increase in the proportion of active complex in the presence of albumin, but not in its absence.
221 6765517 To assess whether human insulin (recombinant DNA) is superior to porcine insulin, we compared the biologic effect of these two insulin preparations on rat and human adipocyte lipogenesis in vitro.
222 6131079 The loss of insulin inhibition of glucagon-mediated somatostatin secretion may account for the hypersomatostatinemia of severe diabetes.
223 6296674 In nondiabetic subjects, beta-endorphin also increased plasma insulin concentrations.
224 6336703 However, phenylephrine, an inhibitor of glucose-induced insulin secretion, stimulated arachidonate turnover in PI. p-Bromophenacyl bromide, an inhibitor of phospholipase A2, markedly depressed both glucose-stimulated arachidonate incorporation into phospholipids and insulin release.
225 6337893 Insulin receptor affinity was significantly higher in subcutaneous than in omental fat cells, but there was no difference in receptor number (about 300,000 sites/cell). 125I-insulin dissociated more rapidly from omental than from subcutaneous adipocytes in both the absence and the presence of excess native insulin.
226 6131815 In the PSDS preparation, diabetes reduced total integrated insulin output by 97% (from 1146 +/- 198 to 40 +/- 24 ng/65 min, P less than 0.001), and glucagon output by about 50% (from 51.6 +/- 13.1 to 24.0 +/- 3.7 ng/65 min, P less than 0.05), whereas somatostatin output did not change (105.5 +/- 48.1 to 110.1 +/- 36.9 ng/65 min).
227 6131850 Cysteamine (300 mg/kg) administered subcutaneously depletes pancreatic somatostatin to 36% of control levels, but does not alter pancreatic insulin or glucagon content.
228 6220614 The effects of insulin, T4, and T3 treatment on cardiac function, myosin ATPase activity, and myosin isozyme distribution were studied in alloxan diabetic rats.
229 6220614 Insulin treatment totally reversed the changes in function, serum thyroid hormones, and myosin ATPase activity.
230 6133785 The size of the somatostatin cells from the gizzard-duodenum junction was negatively related to the magnitude of the glucose-induced insulin release, which suggests an increase in somatostatin cell activity in true insulin-deficient depancreatized chickens as observed in insulin deficient diabetic mammals.
231 6189748 Fasting the rats for 24 h significantly suppressed the insulin and glucagon responses to glibenclamide while the concomitant somatostatin response was slightly enhanced.
232 6134649 The relative hypoglycemic effects of pulsatile versus steadily infused insulin have been examined in six normal subjects in whom pancreatic insulin output was suppressed by somatostatin-14.
233 6134650 In man a small dose of somatostatin (50 micrograms/h) suppressed moderately basal insulin (5 microU/ml) and glucagon (40 pg/ml) levels.
234 6135416 The increase in hepatic lipogenesis in T3-treated 48 h-starved rats after intragastric glucose feeding was prevented by short-term insulin deficiency, but not by (-)-hydroxycitrate, an inhibitor of ATP citrate lyase.
235 6135634 These results suggest that (1) dynorphin is a very potent stimulus for insulin secretion; (2) dynorphin does not affect somatostatin secretion in static incubations of islets, in the same way as does glucose and glyceraldehyde; (3) dynorphin's effects may involve increased calcium ion movement and can be blocked by verapamil; (4) dynorphin can also increase islet c-AMP, and could thereby modulate the responsiveness of other secretagogues; (5) the actions of dynorphin on insulin secretion are not mediated by delta or mu opiate receptors in islets.
236 6135831 Serum human placental lactogen (hPL) and human chorionic gonadotropin (hCG) were assayed and fetal crown-rump length (CRL) was determined by sonar in three groups of pregnant women--35 with uncomplicated pregnancies, 13 with insulin-dependent diabetes mellitus, and 21 who represented a general pregnancy population.
237 6136893 Administration of the somatostatin analogue increased the effectiveness of insulin in controlling postprandial hyperglycemia and permitted satisfactory postprandial glycemic control when the insulin infusion was initiated immediately before meal ingestion.
238 6192127 Administration of insulin to diabetic rats produced an increase in the level of mRNA coding for glucokinase within 20 min and reached a maximum 13-fold increase 1 h following insulin treatment.
239 6137430 In summary, a 46-h infusion of somatostatin with glucagon replacement in humans leads to hyperglycemia, a slightly diminished basal insulin level, markedly decreased insulin responses to glucose, and an insulin response to isoproterenol maintained at a normal level by acute and probably chronic adaptation to the hyperglycemia.
240 6311653 In contrast, tumors of group B are characterized by scarce well-granulated typical B-cells, a medullary-type histologic structure, and irregular insulin immunofluorescence; functionally these tumors show elevated circulating levels of proinsulin-like component and a marked resistance of insulin secretion to somatostatin and diazoxide inhibition.
241 6141177 We conclude that prolonged mild selective insulin deficiency produced by infusion of somatostatin with glucagon replacement in normal men causes an elevation of the fasting plasma glucose level, which is maintained by glucose overproduction rather than by glucose underutilization.
242 6319955 Administration of human beta-endorphin (2.5 mg IV bolus) to three subjects with non-insulin-dependent diabetes mellitus (type II) induced prompt and simultaneous increments in the plasma concentrations of insulin and glucagon lasting up to 90 minutes.
243 6320671 Insulin deficiency was not associated with greater changes in epinephrine-induced activation of glycogen phosphorylase kinase than that observed in normal hearts.
244 6361450 The effect of insulin treatment on the activity of lysosomal acid lipase requires further evaluation.
245 6364673 In diabetic rats with 26.51 +/- 1.89 mmol/l of serum glucose, the plasma renin activity (PRA), plasma aldosterone (PA), immunoreactive insulin (IRI) and urinary excretion of prostaglandin E2 (PGE2) were all significantly lower than in control rats, but the plasma potassium and renal function were not significantly different.
246 6364828 Decreased islet glucokinase would diminish islet glycolysis and would result in a higher set point of beta-cells for glucose-induced insulin release.
247 6400703 In this study the effect on blood glucose, serum insulin, C-peptide, and plasma gastric inhibitory polypeptide (GIP) of giving 75 g glucose in 300 ml over 1 and 10 min (G1 and G10) was investigated in six subjects.
248 6400709 Fourteen insulin-dependent diabetic patients were treated for 6 wk with the alpha-glucosidase inhibitor, acarbose, in a double-blind crossover study to see whether the drug would delay absorption of the evening meal sufficiently to correct the mismatch and prevent nocturnal hypoglycemia.
249 6694560 In summary, inhibition of carnitine palmitoyltransferase 1 by POCA is suggested to be a useful approach for restoring insulin sensitivity depressed by an excessive metabolism of lipids.
250 6143233 We now report structure-activity studies which optimize the potency of this cyclic hexapeptide series with the synthesis of cyclo (N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe), II, which is 50-100 times more potent than somatostatin for the inhibition of insulin, glucagon and growth hormone release.
251 6143305 The present study was designed to determine the effect of naloxone, a specific opiate receptor antagonist, on postprandial levels of insulin, glucagon, pancreatic polypeptide (PP), somatostatin-like immunoreactivity (SLI) and gastrin in response to carbohydrate and fat-rich test meals in a group of 6 healthy volunteers.
252 6200377 Somatostatin (10 micrograms/ml), which inhibits cAMP-stimulated protein phosphorylation, suppresses insulin release evoked by IBMX, glucagon, or forskolin (inhibition: 80, 75, or 82%, respectively).
253 6323236 Insulin causes a 7-10-fold decrease of both the mRNA that codes for rat hepatic phosphoenolpyruvate carboxykinase (mRNAPEPCK) and of PEPCK synthesis, provided the animals are made diabetic and fed chow. mRNAPEPCK, measured either by in vitro translation or cDNA hybridization, decreases with a half-time of 30-60 min after insulin treatment.
254 6323405 These data indicate that insulin regulates hepatic glucokinase synthesis in vivo by increasing glucokinase mRNA; its effect is reduced by the absence of glucocorticoids or thyroid hormones and is rapidly antagonized by cyclic AMP.
255 6323532 Glucagon receptor levels, glucagon-stimulated and other forms of adenylyl cyclase activity, and regulatory component activity of adenylyl cyclase were determined in hepatic plasma membranes of rats administered streptozotocin without and with insulin to produce varying degrees of hyperglycemia.
256 6366551 Insulin requirements increased at least 50 per cent for 1 1/2 hours in 77 per cent of patients with NIDDM and in 75 per cent of patients with IDDM.
257 6366551 In five patients with IDDM who were studied on four occasions, the phenomenon occurred during 17 of the 20 observation periods, with insulin requirements after 6 a.m. increasing 225 +/- 34 per cent; coefficients of variation in individual patients ranged from 4 to 25 per cent.
258 6367775 The effect of insulin and ATP on pyruvate dehydrogenase activity has been studied in a mixture of plasma membranes/mitochondria from normal and diabetic rat brain.
259 6201519 Short-term insulin treatment restores pancreatic amylase and trypsinogen levels to normal but has no effect on serum amylase or pancreatic lipase levels.
260 6232127 The fructose-induced increase in Ca++-activated myosin ATPase activity and alteration in myosin isoenzyme distribution occurred in the absence of changes in insulin and thyroid hormone levels or improvement in the general metabolic status of fructose-fed diabetic rats.
261 6232163 Changes in the expression of different myosin heavy chain genes are most likely responsible for the thyroid hormone and insulin-induced alterations in myosin isoenzyme predominance.
262 6327435 The effect appears to be mediated by the insulin receptors, as: the concentration dependence on insulin is identical to that for insulin induction of tyrosine aminotransferase and stimulation of 2-aminoisobutyric acid transport, proinsulin is 6% as potent as insulin, and the effect is blocked by anti-receptor antibodies.
263 6372155 After 24 hr of strict control, plasma free insulin levels rose significantly, total t-PA R-Ag, its active fibrin binding fraction and euglobulin fibrinolytic activity were significantly decreased.
264 6373459 GIP increased the insulin response to 300 mg/dl glucose threefold in both lean and obese rats.
265 6373459 At basal glucose levels (80 mg/dl), GIP augmented insulin release in obese but not in lean rats.
266 6373459 GIP infusion to achieve levels equivalent to those seen in the basal state are capable of stimulating insulin release in the absence of hyperglycemia in the obese rat, which suggests an impairment of the regulatory mechanisms controlling the glucose-dependent insulinotropic action of GIP in these animals.
267 6235742 Insulin administration rapidly lowered plasma glucose and the elevated glucose-6-phosphatase (G-6-Pase) specific activity of the diabetic rats.
268 6331195 On a normal salt intake, glomerular ANG II receptor density was reduced significantly in untreated diabetic rats (853 +/- 74 (SE) fmol/mg protein), compared with insulin-treated diabetic rats (1,185 +/- 118 fmol/mg) and normal controls (1,058 +/- 83 fmol/mg).
269 6378262 Levels of human placental lactogen (HPL) were significantly elevated in B-noRx patients compared to PC and A and were lowered to levels comparable to normal in insulin-treated B patients.
270 6380308 Patients with IDDM determined to have inadequate glucose counterregulation during an insulin infusion test (40 mU X kg-1 X h-1) with bedside plasma glucose monitoring and clinical observation have been found to have a 25-fold greater risk of severe hypoglycemia during subsequent intensive therapy than patients with adequate glucose counterregulation.
271 6380310 Addition of 1 microM insulin during the culture period led to a 30% decrease in subsequent 125I-insulin binding; the presence or absence of either epidermal growth factor or carbachol was without effect on insulin binding.
272 6094290 Inhibition of insulin degrading activity (IDA) during chloroquine therapy was associated with reductions in the leukocyte lysosomal enzymes alpha-galactosidase and hexosaminidase-A but not hexosaminidase-B and beta-glucuronidase.
273 6238541 Papillary muscle function, actomyosin ATPase, and myosin isoenzyme distribution showed progressive normalization with increasing insulin dose as blood glucose concentration returned to normal.
274 6387483 We conclude that hypoglycemia can cause rebound hyperglycemia in the absence of insulin waning in patients with IDDM, and that this results primarily from an excessive increase in glucose production due to activation of glucose counterregulatory systems.
275 6389225 In competition with 125I(A14)-iodoinsulin for binding to adipocyte receptors at 15 degrees C, proinsulin showed a 100-fold lower affinity for binding than did insulin.
276 2578419 Galanin infusions produced greater parenteral glucose-induced rises in plasma glucose levels along with markedly blunted insulin responses compared with glucose and insulin responses to control glucose infusions.
277 2578419 These results suggest that galanin's hyperglycemic activity is predominantly mediated by a reversible inhibition of insulin secretion.
278 3880552 The effects of putative insulin mediators on the pyruvate dehydrogenase (PDH) activity of intact mitochondria isolated from rat liver were investigated.
279 6085698 This study examined orthograde axonal transport of choline acetyltransferase activity and motor nerve conduction velocity in insulin-treated diabetic and nondiabetic rats of the BB/D strain.
280 6399521 We observed that prolongation of the time period between insulin and meal did not alter the magnitude of the post-meal rise in glucose concentration in the IDDM group.
281 3881645 The mean maximum PFI levels were 39 +/- 7.2, 28.4 +/- 3.4, 36.2 +/- 6.4, and 29.2 +/- 7.6 mus U/mL, respectively, during the U10, U40, and U100 infusions and the U40 bolus injection; these values were observed, respectively, 60, 120, 90, and 90 minutes after a step up increase of insulin infusion and after the SC bolus injection.
282 3881888 In order to ascertain whether or not abnormal mineral and vitamin D metabolism in diabetes can be reversed by insulin therapy, plasma calcium, ionized calcium, phosphorus, parathyroid hormone (PTH) and vitamin D metabolites were measured in control, streptozotocin (STZ) diabetic and insulin-treated diabetic rats.
283 3883096 To determine whether H-TGL activity is altered in insulin-deficient diabetes, postheparin plasma was obtained from eight beagle dogs: three normal (nondiabetic) control dogs and five pancreatectomized diabetic dogs were studied acutely in poor diabetic control (underinsulinized), and again in short-term good control (well insulinized).
284 3883096 Thus, insulin-deficient diabetes in dogs increases H-TGL, and short-term improvement of glycemic control with insulin partially corrects this increase.
285 3883097 To determine whether a delay in carbohydrate absorption would increase the effectiveness of subcutaneous insulin in controlling postprandial hyperglycemia in patients with insulin-dependent diabetes mellitus and whether it could allow insulin to be taken immediately prior to meals, the effects of an alpha-glucosidase inhibitor (Acarbose Boyer AG, Wuppertal, Germany) on postprandial plasma glucose profiles were determined in six subjects with insulin-dependent diabetes when a subcutaneous insulin infusion was started immediately or 30 minutes prior to meal ingestion.
286 3883988 Administration of insulin to control rats did not alter this parameter, but increased the Km for casein of casein kinase 2 in diabetic rats.
287 3971912 Overt insulin-dependent diabetes mellitus in the rat is associated with the u haplotype of the rat major histocompatibility complex (MHC), RT1.
288 3979691 These results do not support the suggestion that continuous subcutaneous insulin infusion stimulates serum amyloid A production or that it carries a risk of inducing reactive systemic amyloidosis.
289 2580790 Insulin treatment had a significant effect on lysozyme and lactoperoxidase activity, recovering 73 and 74% those of the controls, respectively, and the ratio of lactoferrin to total salivary protein reverted to normal values.
290 2581958 The effect of insulin on protein synthesis was associated with a 1.5-fold increase in the amount of Met-tRNAmeti bound to the 1.41 g/cm3 particle.
291 2859985 Reducing circulating fetal insulin levels by injection of streptozotocin was not sufficient to induce TAT enzyme activity.
292 2412919 Isolated rat and mouse acini have insulin receptors, and in these cells, after binding to its receptors, insulin regulates a number of functions including: sugar transport, protein synthesis, and the number of cholecystokinin receptors.
293 2864297 The values from the standard FSIGT were then compared with direct measurements obtained from experiments in which the dynamic insulin response to glucose was suppressed with somatostatin (SRIF).
294 3898867 The effect of streptozotocin-induced diabetes mellitus on maximal insulin-stimulated glucose uptake in the rat was studied in isolated adipocyte, perfused hindlimb, and the intact organism.
295 3899766 The effect of plasma glucose control on retinal morphology, urinary albumin excretion and related haematological and lipid measurements was studied prospectively for 30 weeks in 17 patients with insulin-dependent diabetes mellitus.
296 3900134 Infusion of GIP with peripheral intravenous glucose did not increase hepatic uptake of glucose or the fractional hepatic extraction of insulin compared with peripheral intravenous glucose alone.
297 2866056 Somatostatin was not found to influence the assessment of insulin sensitivity by the insulin sensitivity test.
298 2866128 A gradient of met-enkephalin from 0 to 10(-6) M caused only an inhibition of somatostatin release, whereas insulin release was stimulated.
299 2866128 Naloxone (10(-6) M) alone changed the endocrine secretions by decreasing somatostatin release and by stimulating insulin release.
300 3905185 In 43 patients the insulin antibody response was correlated with HLA A, B, and DR antigens.
301 3905188 In the density separated samples the insulin binding correlated closer to the pyruvate kinase activity than to the number of reticulocytes.
302 3905460 Comparative studies were performed on the relative effects of diabetes and insulin on heparin-releasable adipose lipoprotein lipase (LPL) in the intact and hypothyroid rat.
303 3905460 Insulin stimulated adipose LPL in the Tx-diabetic group.
304 3905460 Furthermore, the magnitude of the adipose LPL stimulation by insulin was not modulated by the endogenous serum T3.
305 3905479 Exogenous copper-zinc superoxide dismutase reproducibly protected the morphological features of pancreatic beta cells against damage by alloxan as determined by light microscopic immunostaining for insulin and by ultrastructural examination.
306 3905968 Porcine insulin conjugated with bovine serum albumin was used for coating microtiter plates.
307 3908279 Insulin promotes proliferation of arterial smooth muscle cells and enhances lipid synthesis and low density lipoprotein receptor activity.
308 3908487 Combinations of PDGF and insulin caused an even more rapid increase in collagen deposition.
309 2867167 To investigate the possibility that metformin (dimethylbiguanide) modifies insulin-mediated glucose metabolism by an effect that is independent of insulin receptor binding, glycogenesis and insulin binding were measured in soleus muscles isolated from streptozocin diabetic mice after treatment with 60 mg kg-1 metformin daily for 10 weeks.
310 2867847 No change in somatostatin release was caused by insulin (25 U/l) during perifusion of freshly isolated islets at 8.3 mmol/l glucose, whereas AIS showed an inhibitory effect.
311 2935351 To determine the relationship between thrombin generation and platelet secretion in vivo in diabetes mellitus, we measured simultaneous plasma beta-thromboglobulin (BTG) and fibrinopeptide A (FPA) in 40 insulin-dependent patients without renal disease, and 20 control subjects of similar age.
312 3002934 We have studied the effect of insulin hypoglycemia on the secretion of pancreatic polypeptide (PP) in 14 obese subjects with normal glucose tolerance and in 6 normal controls.
313 3910488 To investigate whether metabolic decompensation has an effect on gastric inhibitory polypeptide (GIP), 8 fasting male type 1 diabetics were deprived of insulin for 12 h.
314 3936737 Met-enkephalin, catecholamines and prostaglandin E (PGE) have all been reported to inhibit the acute insulin response to glucose in normal humans.
315 4092861 Type IV collagen antigen crossreacting with antibodies to the C-terminal domain was elevated from 32.0 +/- 5.36 ng/ml (n = 10) in serum of normal rats to 94.9 +/- 24.5 ng/ml (n = 10, P less than 0.0001) in serum of streptozotocin diabetic rats and could be normalized to 40.1 +/- 8.30 ng/ml (n = 18) by insulin treatment.
316 2420523 Pineal levels of tryptophan, 5-hydroxytryptophan, serotonin, N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid and the enzyme activities of N-acetyltransferase and hydroxyindole-O-methyltransferase were determined in male albino rats and Syrian hamsters that were injected with insulin twice daily for three days, or injected with streptozotocin to induce diabetes.
317 3516750 We have determined peripheral venous somatostatin like immunoreactivity (SLI) levels in 11 normal subjects (blood glucose--BG--: 4.4 +/- 0.1 mM; ketone bodies--KB--: 90 +/- 12 microM; plasma free fatty acids--FFA --: 340 +/- 42 microM), 4 Biostator controlled insulin dependent diabetics (BG: 5.4 +/- 0.2 mM; FFA: 418 +/- 38 microM; KB: 226 +/- 41 microM) and 7 poorly controlled ketotic diabetics (BG: 10.8 +/- 1.3 mM; FFA: 915 +/- 19 microM; KB: 2490 +/- 576 microM).
318 3516835 The effects of insulin or oral agent treatments on the plasma lipoproteins and lipoprotein lipase activator were compared in a strictly defined non-obese, non-insulin dependent diabetic patient.
319 3516835 Lipoprotein lipase activator contents of the very low density lipoproteins correlated positively with their triglyceride (r = 0.803 in insulin, r = 0.828 in oral agent treated patients) and protein (r = 0.713 in insulin, r = 0.862 in oral agent treated patients) contents.
320 3518119 The basal level of serum gastrin was determined by radioimmunoassay in 144 patients with insulin-dependent diabetes mellitus.
321 3701514 In most patients, a gluten-free diet had little effect on insulin dosage, urinary excretion of glucose, or serum level of hemoglobin A1.
322 3091164 The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria.
323 3527808 PDHa and PDHt activity reaches a maximum of stimulation at 25 microU/ml insulin; the activation is reduced at higher concentrations of insulin though no inhibition appears.
324 3527826 We have previously suggested that insulin effects on 2-deoxyglucose (2-DOG) uptake in BC3H-1 myocytes are due to increases in de novo phospholipid synthesis, diacylglycerol generation, and protein kinase C activation.
325 3527826 These findings support our hypothesis that diacylglycerol generation and protein kinase C activation may be important in the stimulation of glucose uptake by agents such as phenylephrine and insulin that activate the phosphoinositide cycle.
326 3528867 Growth hormone and insulin act mainly by modulating the hepatic synthesis of IGF-I.
327 2876005 SMS 201-995 is a new somatostatin analog which is 10-60 times more potent and specific than somatostatin as an inhibitor of GH and insulin release.
328 2876501 Native somatostatin has multiple actions, including inhibition of the secretion of insulin, glucagon, thyroid-stimulating hormone (TSH), and various gut hormones.
329 3489237 Insulin-dependent diabetes mellitus (IDDM) susceptibility determinants are known to be associated with both HLA-DR3 and -DR4.
330 3530596 The direct effects of insulin and glucose on bone modelling was studied in an in vitro system. 16 day old mice fetal radii and ulnae prelabelled with 45Ca were cultured for 48 hr in BGJ medium supplemented with either 4 mg/ml of human serum albumin or 10% fetal calf serum.
331 3530724 The receptors were highly specific for insulin, with 60% inhibition of insulin binding by an antireceptor antibody, no competition by epidermal growth factor, and an ED50 of 300 nM for proinsulin.
332 3530724 Chloroquine (100 microM) inhibited intracellular processing of insulin, leading to a 300% increase in cell-associated insulin by 2 h (37 C).
333 3530724 After exposure to insulin for 24 h, alkaline phosphatase activity was decreased compared to basal by 39.5% and 50% with 5 and 50 ng/ml insulin, respectively.
334 3530857 The antiketogenic effects of insulin and proinsulin were associated with an increased glycerol 3-phosphate content and a decreased affinity of carnitine palmitoyltransferase for its substrate palmitoyl-CoA.
335 3751446 Several lysosomal enzymes (beta-N-D-acetylglucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase, beta-D-galactosidase, alpha-L-fucosidase, alpha-D-glucosidase, alpha-D-mannosidase, beta-D-glucosidase), glycated albumin and glycated hemoglobin (HbA1c) were determined in the serum of 81 insulin-dependent diabetics with different degrees of metabolic control (optimal, 21 patients; good, 39 patients; poor, 21 patients) and without signs of complications, and in 42 control subjects.
336 2878175 36 patients with insulin-dependent diabetes mellitus who had 'Albustix'-negative urine but raised urinary albumin excretion (30 to 300 mg/24 h) were randomly assigned to either remaining on conventional insulin treatment or continuous subcutaneous insulin infusion and followed up for 2 years.
337 2878175 Insulin infusion had an overall beneficial effect on the annual increase in urinary albumin excretion (p less than 0.05), and the mean glycosylated haemoglobin values correlated positively with annual change in albumin excretion (r = 0.57, p less than 0.0001).
338 2946569 PNMT activity was approximately 2-fold higher in the brainstem of diabetic rats than in controls (P less than 0.0001), and administration of insulin partially prevented the effects of diabetes on PNMT activity (P less than 0.01 compared to diabetics and P less than 0.05 compared to controls).
339 3024509 In diabetics, combined cold exposure and insulin did not affect the increase in BAT growth or LPL activity resulting from either treatment alone, but in controls this combination decreased BAT growth and COA.
340 3536368 These results suggest that the decreased clearance of insulin is due to the decreased receptor binding and the decreased receptor-mediated degradation, but is not due to the decreased degradation by IDE.
341 3537254 Adipose tissue from PGF-treated intact and hypophysectomized rats had significantly elevated basal glucose oxidation rates, and the tissue was sensitive to further stimulation by insulin or hGH.
342 2435221 Both are mitogenic and IGF-II has more insulin-like effects than does SM-C/IGF-I.
343 2878848 Somatostatin (SRIF) has been widely used in the study of in vivo carbohydrate metabolism to suppress pancreatic hormone secretion and thereby interrupt the glucoregulatory feedback loops between insulin, glucagon, and glucose.
344 2879758 Endogenous insulin and glucagon secretion were inhibited by somatostatin (0.8 micrograms X kg-1 X min-1), and intraportal replacement infusions of insulin (213 +/- 28 microU X kg-1 X min-1) and glucagon (0.65 ng X kg-1 X min-1) were given to maintain basal hormone concentrations for 2 h (12 +/- 2 microU/ml and 108 +/- 23 pg/ml, respectively).
345 3491769 The HLA association with insulin-dependent diabetes mellitus is highest among individuals heterozygous for DR3 and DR4.
346 3542649 This result provides direct confirmation that insulin is not associated with a circulating serum binding protein(s) and that insulin is present predominantly as a monomer in plasma.
347 3543053 The insulin receptor contains an alpha subunit with insulin binding properties and a beta subunit with insulin-stimulated tyrosine kinase function.
348 3803736 We conclude that a decreased carbohydrate tolerance associated with winter can explain the seasonal variation in the incidence of IDDM and that this seasonality is caused by the precipitation of overt carbohydrate intolerance in individuals with already seriously compromised insulin secretory capacity.
349 3803738 In perfused lean rat hearts, the activator of protein kinase C phorbol myristate acetate (PMA), when present alone, stimulates glucose transport but inhibits the insulin stimulation of this transport.
350 3803738 In contrast, none of these effects are observed in hearts and hepatocytes of obese animals, indicating an impaired protein kinase C activation in these tissues, which are insulin resistant.
351 3803738 Pretreatment of lean rats with PMA in vivo, aimed at downregulating protein kinase C, induces the same defects (i.e., insulin resistance and unresponsiveness to PMA) as those observed in hearts of untreated obese animals.
352 2880702 In Study B, endogenous secretion of IRI and IRG was suppressed by infusion of somatostatin (0.2 microgram/kg/min), while peripheral concentrations were maintained constant by replacing glucagon (0.65 ng/kg/min) and insulin (0.225 mU/kg/min).
353 2950085 Administration to normal rats of 100 mg of streptozotocin/kg body weight produced ketotic diabetic rats in which the affinity of carnitine palmitoyltransferase for malonyl-CoA was decreased by 10-fold and its activity was increased by 30%, but the injection of insulin brought the affinity and the activity back to normal within 4 h.
354 2950085 The total activity of mitochondrial carnitine palmitoyltransferase (outer + inner activities) was 40% greater in the BB Wistar diabetic rat, but treatment with insulin did not decrease the total activity to normal values within 2 h.
355 2950085 Insulin acts on the outer carnitine palmitoyltransferase to reverse these effects very rapidly, but diabetes produces some change in the total activity that is not reversed by short-term treatment with insulin.
356 2950929 Serum EGF concentrations measured were almost the same among the control, diabetic, and insulin-treated diabetic groups.
357 2950929 These results suggest that insulin deficiency in vivo causes a decrease in hepatic EGF receptors.
358 2951221 To investigate whether morning or evening injection of a long-acting insulin preparation (Ultratard HM, Novo) affects the glycaemic control in insulin-dependent diabetic (IDDM) patients, 24-hour blood glucose and plasma free insulin profiles were obtained in nine C-peptide negative IDDMs after one daily injection of insulin Ultratard HM either before breakfast (0800 h) or at 2200 h during the preceding 14 days.
359 2951394 To address the possibility that an abnormality in pancreatic beta-endorphin activity might contribute to abnormal insulin secretion in diabetes mellitus, we studied the effects of beta-endorphin infusion on islet function in diabetic patients.
360 2951394 The iv infusion of human beta-endorphin at a dose of 0.5 mg/h for 2 h in type-2 non-insulin-dependent diabetic patients (n = 12) raised plasma insulin and glucagon levels and slightly but significantly lowered plasma glucose concentrations. beta-Endorphin infusion also resulted in reappearance of a clear-cut acute insulin response to glucose, while second phase insulin release was increased and glucose disposal accelerated.
361 2951394 Acute insulin and glucagon responses to arginine were not increased by beta-endorphin, suggesting that the effect of the opioid on the B cells of the diabetic patients is specific for glucose.
362 3030412 A major effect of insulin in vitro upon diabetic liver was the induction of a large increase in the rate of pyruvate kinase flux, bringing relative and absolute fluxes up to the levels measured in 24-h-fasted controls.
363 3547015 The administration of the long-acting met-enkephalin analogue (FK 33-824, Sandoz; Basel Switzerland) inhibits insulin secretion induced by glucose (oral and intravenous) and nonglucose (arginine and breakfast) secretagogues in both normal subjects and in patients with noninsulin-dependent diabetes mellitus.
364 3548715 Cytochrome P-450 dependent hydroxylation of testosterone has been measured in hepatic microsomes of control, diabetic and insulin-treated diabetic rats.
365 3549258 Glomerular angiotensin II receptors were measured by Scatchard analysis; insulin, renin activity, angiotensin II, and aldosterone were measured by RIA.
366 3549325 Miglitol is an alpha-glucosidase inhibitor which lowers blood glucose and insulin concentrations in healthy volunteers after a starch meal.
367 3817304 We measured glycosylated albumin and hemoglobin and serum protein binding of phenytoin in 57 children and adolescents with insulin-dependent diabetes mellitus (IDDM).
368 2882748 However, when insulin secretion was inhibited, either by the induction of streptozotocin-diabetes or by simultaneous infusion of somatostatin, glucagon treatment was able to depress the expressed activity of HMG-CoA reductase (i.e. it increased the phosphorylation of the enzyme).
369 2883057 We have previously shown that a nonimmunoreactive analogue of somatostatin, (D-Ala5, D-Trp8)-somatostatin, differentially inhibits pancreatic somatostatin secretion without inhibiting insulin or glucagon secretion.
370 2883057 Pancreatic insulin output increased 10-fold, pancreatic somatostatin output increased from 1.2 +/- 0.3 to 3.0 +/- 0.8 ng/min, and pancreatic glucagon output was suppressed from 1.4 +/- 0.7 to 0.5 +/- 0.1 ng/min.
371 2883058 C-peptide was equally suppressed by hypoglycemia regardless of whether somatostatin was administered, indicating suppression of endogenous insulin during these studies.
372 3032718 The opiate receptor antagonist naloxone (1 mg/kg intraperitoneally) rapidly and transiently raised glucose and suppressed insulin concentrations in lean mice, and produced qualitatively similar but more protracted response in ob/ob mice.
373 3033025 Two metabolic sequelae of hyperglycemia in diabetic nerve, sorbitol accumulation via aldose reductase, and (Na,K)-ATPase deficiency related to myo-inositol depletion, were explored as possible underlying causes of acute paranodal swelling in the spontaneously diabetic bio-breeding rat. 3 wk of insulin replacement, or therapy with an aldose reductase inhibitor or myo-inositol completely reversed paranodal swelling in sural nerve fibers after 3 wk of untreated insulin deficiency.
374 3552532 Therapy with oral agents or insulin, resulting in good glycemic control, is followed by an increase of LPL activity in both adipose tissue and postheparin plasma.
375 3552532 In chronically insulin-treated patients with high LPL activity, VLDL triglyceride concentrations are normal or subnormal, and HDL level is increased.
376 3552798 Fed plasma glucose concentrations increased in the NSIR between 4 and 5 wk and were significantly elevated at 8 wk (251 +/- 25 vs. 527 +/- 52 mg/dl, P less than .001). 125l-labeled insulin binding showed a progressive increase as a function of adipocyte volume in control and NSIR.
377 3569629 The effect of rapid daily variation of glycemia and labile HbA1 on both antithrombin III (ATIII) activity and plasma concentration in ten insulin dependent diabetics has been evaluated.
378 2884157 We conclude that in IDDM and in totally pancreatectomized patients, administration of insulin with subsequent normalization of blood glucose is accompanied by a decline in plasma levels of SLI in the fasted state, whereas the apparent response to a meal is enhanced.
379 2884158 We conclude that basal and stimulated gastric SLI release is increased in untreated BB rats and is suppressed with insulin therapy, gastric delta-cell hyperfunction accounts for portal vein hypersomatostatinemia characteristic of untreated diabetic BB rats, and somatostatin-14 is the main molecular form of SLI released from normal and diabetic stomachs.
380 3296383 Specific adipocyte receptor binding of insulin and the effects of the hormone on glucose oxidation and lipolysis were determined in subcutaneous adipose tissue.
381 3556105 The urinary excretion of albumin in the diabetic subjects was not associated with the presence of hypertension or coronary heart disease or with the fasting blood glucose or serum insulin levels measured at diagnosis of diabetes.
382 3584394 Body weight and insulin requirement correlated directly with HTGL activity and inversely with serum HDL cholesterol levels.
383 2886385 These studies were performed with a clonal cell line of glucose-responsive beta-cells (HIT cells) to determine whether PGE2 effects on insulin secretion are receptor mediated and, if so, whether the postreceptor effects are mediated by inhibitory regulatory components (Ni) of adenylate cyclase.
384 2886385 Maximum inhibition of glucose-induced insulin secretion was 26, 37, and 29% of control values for somatostatin, PGE2, and epinephrine, respectively.
385 3109862 Peak and integrated cortisol, GH, and catecholamine responses to insulin and proinsulin were similar, but those of prolactin were reduced after proinsulin when compared with insulin by 42% (P less than .01) and 34% (P less than .05), respectively.
386 3109862 The intravenous injection of a dose of proinsulin (6 micrograms/kg), which did not produce hypoglycemia but was the molar equivalent of insulin used in the first protocol, failed to modify the GH or prolactin responses to a combined injection of GH-releasing hormone (1 microgram/kg) and thyrotropin-releasing hormone (500 micrograms).
387 3297891 The effects of interleukin 1 (IL-1) on glucose-induced insulin secretion from isolated rat islets of Langerhans have been examined.
388 3297891 IL-1 both inhibits and stimulates glucose-induced insulin secretion depending on the experimental design.
389 3301157 The cells produced 63 +/- 3 ng (mean +/- SD) immunoreactive insulin and 9.4 +/- 0.3 ng immunoreactive glucagon per day per 10(6) cells, while somatostatin (SRIF) and pancreatic polypeptide (PP) were undetectable.
390 3301474 Insulin stimulated myosin and LDH synthesis by 169 and 184%, respectively.
391 3595966 In order to investigate the endocrine pancreatic dysfunction resulting from iron overload, plasma pancreatic polypeptide (PP) response to a protein-rich meal was studied in 10 healthy controls and 30 insulin-dependent (type I) diabetic patients: ten with idiopathic haemochromatosis (IH), ten with chronic pancreatitis and ten with idiopathic type I diabetes.
392 2957293 Serum EGF concentrations measured were almost the same among the control, diabetic, and insulin-treated diabetic groups.
393 2957293 These results suggest that insulin deficiency in vivo causes a decrease in hepatic EGF receptors.
394 3040496 We have recently shown that interferon-gamma (IFN-gamma) markedly upregulates the expression of the class I major histocompatibility proteins on pancreatic beta cells and have therefore postulated that interferon-gamma may enhance cytotoxic lymphocyte-mediated beta cell damage in insulin-dependent diabetes mellitus.
395 2888696 Human insulin and C-peptide were infused intraportally into conscious dogs (n = 11) at equimolar rates; endogenous insulin and C-peptide release were suppressed with somatostatin (0.8 micrograms . kg-1 . min-1).
396 2958492 The IGFs inhibited fat cell glycerol release and stimulated adipocyte 3-O-methylglucose transport and adipose tissue glucose oxidation as effectively as did insulin, but the biological potencies of the IGFs, on a molar basis, were 600-1000 times less than that of insulin.
397 2958492 In contrast, IGF-I inhibited [125I]insulin binding with a molar potency 1600 times lower than that of native insulin.
398 2958492 However, the IGFs definitely produce acute insulin-like effects in the human adipocyte, which seems to be mediated via the insulin receptor.
399 3307403 At the end of 10 weeks, insulin administration was associated with a more rapid decrease in the levels of fasting plasma glucose, two-hour postprandial glucose, and glycosylated hemoglobin, but there was no significant difference between the two therapies by the end of the study.
400 3308437 In the present study we have investigated the effects of IL-1 and two other cytokines, namely tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) on the pancreatic B cell paying particular attention to insulin production and glucose metabolism.
401 3308584 Although both forms of therapy improved chronic glycemic control (glycosylated hemoglobin concentration went from 9.6 +/- 0.7 to 7.6 +/- 0.5 and 7.1 +/- 0.2%, respectively, P less than .01), exogenous insulin resulted in a lower postprandial glycemic response than tolazamide (P less than .001).
402 3308589 It has been suggested that the gut hormone cholecystokinin (CCK), by modulating insulin output from pancreatic beta-cells, plays an important role in the enteroinsular axis.
403 3652616 Size exclusion chromatography of acid/ethanol extracts of sera on a Bio-Rad P2 column revealed the presence of a Mr 300-400 inhibitor of insulin-stimulated lipogenesis in 32 (70%) of 46 NIDDM sera but not in 9 IDDM or 12 control sera.
404 2444209 Diabetes, starvation and high-fat diet all caused a fall in the hepatic PPRibP content, whereas insulin treatment and high-carbohydrate diet raised the tissue content.
405 2959439 Guar ingestion reduced postprandial insulin and enteroglucagon responses, the latter significantly so, but had no apparent effect on gastric inhibitory polypeptide, pancreatic glucagon, gastrin, and pancreatic polypeptide.
406 3311550 We conclude that inhibition of intestinal alpha-glucosidases by Bay-m-1099 in IDDM reduces meal insulin requirements by at least 20% and that such an agent could be useful in the management of diabetes mellitus by reducing hyperinsulinemia.
407 3313390 Infusion of a low dose of insulin (2 units per kg per day) into the JV had no effects on the hyperglycemia, body weight gain, tail growth, tibial epiphysial cartilage plate thickness, or serum levels of somatomedin C in the diabetic rats.
408 2890501 Glyburide increased basal and meal-but not glucagon-stimulated insulin and C-peptide levels, and also augmented the effect of meals on somatostatin release.
409 2960133 We have observed that the conversion of 3T3-L1 and 3T3-F442A preadipocyte clones to the adipocyte phenotype, in response to appropriate differentiation stimuli (fetal calf serum, insulin, dexamethasone, and 1-methyl-3-isobutylxanthine), is blocked by DHEA and other steroidal inhibitors of glucose-6-phosphate dehydrogenase.
410 3315515 After the 8-wk program, glycemic control, as measured by glycosylated serum albumin and blood glucose values (but not by glycosylated hemoglobin), improved in the supervised-exercise group despite reduced daily insulin dosage.
411 3318463 At initial presentation, glycosylated hemoglobin concentration was increased in the 18 women who required insulin compared with the 14 women managed by diet alone (7.1% +/- 0.2% versus 6.2% +/- 0.2%, mean +/- SEM, p less than 0.01).
412 2829328 Insulin treatment for 10 days partially normalized serum ACE activity.
413 2829328 Therefore, STZ-induced diabetes produced significant changes in ACE activity that are partially corrected by insulin treatment.
414 2894431 The effect of proglumide ((+/-)-4-benzamido-N,N-dipropyl-glutaramic acid), a gastrin and cholecystokinin receptor antagonist, has been studied on the fasting plasma glucose (FPG) and insulin levels in normal and alloxan-diabetic mice.
415 2963888 Both orchidectomy and insulin deficiency depressed serum concentrations of 1,25-(OH)2D3 (-22 and -45% respectively) and DBP (-14 and -29% respectively), but the effects of insulin deficiency were greater than those of androgen withdrawal.
416 3124871 The adipocyte was found to be a sensitive model for insulin activation of this enzyme.
417 3124871 The present studies indicate that the isolated human subcutaneous adipocyte may serve as a useful model for in vitro investigation of the effects of insulin on glycogen synthase.
418 3327177 Relations between lowered blood capability to degenerate insulin in diabetes mellitus and a rise of antiinsulinase activity of the plasma with preserved normal insulinase activity of erythrocytic hemolysate were established.
419 2896134 The present study was aimed at characterizing the effects of beta-endorphin on plasma glucose, insulin and glucagon plasma levels in subjects with type-2 diabetes mellitus.
420 2896134 Infusion of 0.5 mg/h human beta-endorphin produced significant and simultaneous increments in both insulin and glucagon concentrations and decreased plasma glucose levels (-18 +/- 4 mg/dl, 60 min level, p less than 0.01).
421 2896134 Naloxone (5 mg), an opiate antagonist, did not produce any significant change in the insulin and glucagon responses to beta-endorphin, while somatostatin (0.25 mg/h) completely abolished the hormonal responses to the opioid.
422 2449974 We have produced transgenic mouse strains harboring class II major histocompatibility complex or interferon-gamma genes linked to the human insulin promoter.
423 2833110 To determine if other tyrosine kinases might be altered, we have studied the epidermal growth factor (EGF) receptor kinase in wheat germ agglutinin-purified, Triton X-100-solubilized liver membranes from streptozotocin (STZ)-induced diabetic rats and the insulin-deficient BB rat.
424 2833110 Thus autophosphorylation of EGF receptor, like that of the insulin receptor, is decreased in insulin-deficient rat liver.
425 2964980 The urinary excretion of prostaglandin E2 was significantly elevated in 8 insulin-dependent diabetic patients with incipient nephropathy as compared with 9 normoalbuminuric IDDM patients and 11 healthy controls: 317 (182-1273); 95 (67-225); 132 (54-263) pg/min, respectively (2p less than 0.01).
426 3279808 Insulin at 8 x 10(-10) M increased the accumulation of [14C]glucose in mesangial cells, whereas IGF-I was 10-fold less potent.
427 3279941 The most marked change during insulin therapy was a 2.3-fold increase in adipose tissue lipoprotein lipase (LPL) activity (p less than 0.001).
428 3279941 The data indicate that intensive insulin therapy induces antiatherogenic changes in serum lipids and lipoproteins and suggest that the induction of LPL by insulin is the major factor responsible for redistribution of HDL particles from HDL3 to HDL2.
429 3280182 The CD25 positivity and insulin proliferation were associated to the duration of symptoms before the diagnosis of IDDM.
430 2453340 Insulin release was 97% inhibited after 6 h of incubation in RPMI-1640 medium (11 mM glucose) containing 1 U/ml IL-1 and 96% inhibited after 24 h of incubation in medium containing 0.1 U/ml IL-1.
431 2453340 The cell content of insulin in the monolayers was decreased by 66% (P less than 0.01) after 4 days of incubation in 10 U/ml IL-1; however, after a further 8-day incubation in IL-1-free medium, cell insulin content recovered fully.
432 2966883 Specific binding of both IGF-I and insulin in placental membranes from patients with good glycemic control (as reflected by blood hemoglobin content) was unaltered while that in the placental membranes from the patients with poor glycemic control was increased to approximately 20% of the normals.
433 3130257 In order to study the effects of two new alpha-glucosidase inhibitors with long (BAYo1248) and short (BAYm1099) duration of action on glycaemic control, seventeen insulin-dependent diabetics were connected to the Biostator for 24 h and postprandial hyperglycaemia, insulin requirements and breath H2 concentrations were assessed under three conditions: (a) before administration of any alpha-glucosidase inhibitor (control experiments), (b) after administration of BAYo1248 (40 mg before breakfast, nine patients) or BAYm1099 (100 mg before breakfast and dinner, eight patients) for 1 month, (c) after 1-month administration of placebo (double-blind crossover study).
434 3282856 This study describes insulin binding to circulating monocytes in 24 children with insulin-dependent diabetes mellitus (IDDM), five children with non-insulin-dependent diabetes mellitus (NIDDM), and 10 healthy and 12 obese control children.
435 3282856 Insulin binding to monocytes was greatly increased in untreated IDDM children with obvious ketoacidosis (5.51 +/- 3.49 vs. 1.91 +/- 0.47 pg/10(6) cells, P less than 0.01), whereas it was decreased in those without obvious ketoacidosis (1.39 +/- 0.30 vs. 1.91 +/- 0.47 pg/10(6) cells, P less than 0.01).
436 3282941 To determine the effects of insulin on dietary and endogenous leucine metabolism, five normal subjects, seven insulin-insufficient insulin-dependent (IDDM) diabetic patients, and five diabetic patients controlled with continuous subcutaneous insulin infusion (CSII) were studied before and for 8 h after ingestion of a chemically defined elemental test meal (10 cal/kg) containing crystalline amino acids.
437 3284417 Similarly, the activity of the hepatic lipogenic enzyme, malic enzyme, increased at initial insulin dosages and reached maximal levels at 2 + 2.
438 3286168 Bay-m-1099, a new alpha-glucosidase inhibitor, was given along with insulin immediately before standard breakfasts, lunches and dinners to nine insulin-dependent diabetic patients to determine whether this combination therapy would produce postprandial glycemic control comparable to that achieved when insulin alone was administered 30 min prior to eating.
439 3286168 Thus, the combination of immediate preprandial administration of an alpha-glucosidase inhibitor along with insulin resulted in glycemic control comparable to that achieved when more insulin was taken 30 min prior to eating.
440 3286168 We conclude that use of alpha-glucosidase inhibitors could lessen the inconvenience of intensive insulin regimens by permitting patients to take their insulin immediately before eating and thus result in greater patient compliance.
441 3286334 Absorption studies indicated that autoantibodies against p73 recognized a common epitope on insulin and IgE-binding factor.
442 3286489 The results indicate that the cells responding to insulin were T cells mainly of the helper (CD4+) phenotype and that they required adherent cells of the monocyte/macrophage lineage for proliferation to occur.
443 2454647 The plasma immunoreactive insulin profiles were determined during a 6 h post injection period in subjects receiving concomitantly somatostatin to suppress endogenous insulin secretion. 2.
444 2898831 Therefore, the unimpaired increase in the cell surface area of parathyroid cells in insulin deficient and short-term diabetic rats indicates that insulin does not modulate the release of parathyroid hormone.
445 2898855 It is concluded that somatostatin reduces insulin resistance following hypoglycemia in patients with IDDM.
446 2900090 Somatostatin has been widely employed in studies of hepatic metabolism to suppress the endogenous secretion of the pancreatic hormones, insulin and glucagon.
447 2969796 Thus, insulin action mediated through the IGF-I receptor may initiate growth-promoting tissue effects in the face of limited insulin effect on glucose metabolism.
448 3041640 Pancreatic polypeptide (PP) deficiency has been associated with impaired hepatic sensitivity to insulin and pancreatogenic diabetes in chronic pancreatitis.
449 3041683 These findings indicate that the amount of cytochrome P-450 isozyme involved in the oxidation of 3-methyl group may be regulated by insulin. 5.
450 3042030 The morphological data correlate well with the previously reported evolution of plasma and pancreatic hormone concentration after surgery, and suggest that the normal inhibitory control of glucagon and insulin secretion by the local release of somatostatin might be reduced or suppressed during transient diabetes in subtotally depancreatized ducks.
451 3292327 Insulin significantly and dose dependently inhibited the vasoconstriction induced by NE (10(-8) M for the artery and 10(-7) M for the vein) at greater than or equal to 1.2 mU/ml for both the artery and vein and the vasoconstriction induced by ANG II (3 x 10(-10) M for the artery and 3 x 10(-9) M for the vein) at greater than or equal to 1.2 mU/ml for the artery and greater than or equal to 12 mU/ml for the vein.
452 3292329 Peritoneal macrophages isolated from insulin-deficient mice secreted 70% less LPL activity than control mice.
453 3292329 A 65% decrease in LPL activity in epididymal adipose tissue, without any changes in heart LPL activity, was also seen with insulin deficiency.
454 3292329 Additionally, 1 wk of insulin treatment increased LPL secretion by macrophages, but to only one-half of control, while normalizing adipose tissue LPL activity.
455 3391498 With this RIA method, the following results were obtained: 1) These GA values were correlated with GA values, measured by boronate-affinity chromatographic method. 2) Average of GA values in 44 diabetics was significantly higher than that of 24 normal subjects. 3) These GA values were also correlated with HbA1, HbA1c, and fasting blood sugar (FBS). 4) These GA values were more closely correlated with FBS, 2 weeks before, than with FBS, at the same time, and with FBS, 4 weeks before. 5) After insulin treatment to untreated diabetics, these GA values were more rapidly decreased than HbA1c.
456 2457028 Thus, although lipocortins 1 and 2 are in vitro substrates of the insulin receptor kinase, only lipocortin 1 is phosphorylated in an insulin-dependent manner in intact hepatocytes, and this is only observed after dexamethasone treatment of the rats.
457 2457528 The nonadrenergic component may be mediated by the 29-amino acid peptide galanin in that this neuropeptide meets several of the criteria necessary to be considered a sympathetic neurotransmitter in the endocrine pancreas. 1) Galanin administration inhibits basal insulin and somatostatin secretion and stimulates basal glucagon secretion from the pancreas, qualitatively reproducing the effects of sympathetic nerve stimulation.
458 2457528 If galanin is a sympathetic neurotransmitter in the endocrine pancreas, it may contribute to the inhibition of insulin secretion that occurs during stress and thereby to the hyperglycemic response.
459 2457528 Moreover, the local presence of this potent beta-cell inhibitor in the islet leads to speculation on galanin's contribution to the impairment of insulin secretion that occurs in non-insulin-dependent diabetes mellitus and therefore on the potential utility of a galanin antagonist in the treatment of this disease.
460 2842060 Mutation of the beta-subunit of the insulin receptor by substitution of tyrosyl residue 960 with phenylalanine had no effect on insulin-stimulated autophosphorylation or phosphotransferase activity of the purified receptor.
461 2843407 A suppression of LDL-receptor activity resulting from deficiency of insulin and elevated plasma catecholamine concentrations in uncontrolled insulin-dependent diabetic patients may contribute to the increased levels of LDL cholesterol observed in these patients.
462 2901377 This study explores, using perifused pancreatic slices, whether the reduced B-cell responsiveness to somatostatin in mdb/mdb mice can be overcome upon induction of a biphasic insulin release by using theophylline.
463 2970411 Acute insulin and C-peptide responses to intravenous pulses of different glucose amounts (0.33 g/kg and 5 g) and arginine (3 g) were significantly reduced by beta-endorphin infusion (P less than .01).
464 2970411 This effect was associated with a significant reduction of the glucose disappearance rates, suggesting that the inhibition of insulin was of biological relevance. beta-Endorphin also inhibited glucose suppression of glucagon levels and augmented the glucagon response to arginine.
465 2970411 After stabilization of plasma glucose levels (350 +/- 34 mg/dl, t = 120 min), beta-endorphin infusion caused an immediate and marked increase in plasma insulin level (peak response 61 +/- 9 microU/ml, P less than .01), which remained elevated even after the discontinuation of opioid infusion.
466 3044171 Insulin, within 2 hr, increased the ADH activity found in fasted animals by 28% (p less than 0.02).
467 3044171 Insulin administration failed to stimulate the reduced ADH activity in diabetic rats.
468 3044365 We now report that in normal rats insulin directs a specific increase in malic enzyme mRNA, while albumin mRNA levels remain unaltered.
469 3044889 To evaluate possible mechanisms by which insulin inhibits hepatic apolipoprotein B (apoB) secretion, we incubated primary cultures of rat hepatocytes with sodium orthovanadate, a phosphotyrosine phosphatase inhibitor and insulin-mimetic agent.
470 3044889 Unlike insulin, vanadate, at a concentration that inhibited apoB secretion (10 microM), had no effect on intracellular lipogenesis, inhibited the secretion of newly synthesized hepatic proteins, and had a delayed onset and termination of action on inhibition of apoB secretion.
471 3044889 In conclusion, our data indicate that vanadate mimics insulin action in hepatocytes with regard to the inhibition of medium accumulation of apoB.
472 3046964 A mechanistic understanding of the effects of IL-1 on the beta-cell may clarify its role in modulating insulin release in vivo or yield insight into the pathogenesis of IDDM.
473 3136960 These results confirm the presence in IDDM patients of an imbalanced cellular immune response and demonstrate that the IL-2 deficiency is already present at the diagnosis and is not correlated with insulin administration.
474 3407769 Adipocytes treated with neuraminidase show markedly reduced responsiveness to insulin without any alteration in insulin binding.
475 3407769 At a concentration of neuraminidase that decreases insulin action by 50%, 23% of total cellular sialic acid content was released.
476 2458910 Dexamethasone-induced changes in insulin and epidermal growth factor (EGF) receptor number, autophosphorylation, and kinase activity were studied in intact rat hepatocytes.
477 3050367 Pyruvate dehydrogenase (PDH) activity of NZO mouse adipocytes was totally unresponsive to insulin in contrast to the impaired but still significant insulin stimulation of glucose transport and utilization, suggesting a postreceptor defect at the level of insulin stimulation of this enzyme.
478 3050367 This study demonstrates in adipocytes of NZO mice: (1) a receptor defect and (2) a postreceptor defect of insulin action at the level of pyruvate dehydrogenase activation.
479 3050530 We now report that human pancreatic amylin and rat CGRP-1 are potent inhibitors of both basal and insulin-stimulated rates of glycogen synthesis in stripped rat soleus muscle in vitro.
480 3051005 In skeletal muscle exposed to 120 nM amylin for 1 hr, there was a marked decrease in both basal and submaximally insulin-stimulated rates of glycogen synthesis, which resulted in significant reduction in the rates of insulin-stimulated glucose uptake.
481 3051005 In marked contrast, amylin had no effect on either basal or insulin-stimulated rates of glucose incorporation into either CO2 or triacylglycerol in isolated adipocytes.
482 3051336 Advantages, disadvantages and logistic problems of the change to exclusive use of U-100 insulin, and the possibility of pharmacological differences between insulins of different concentrations, are discussed.
483 3139756 Exposure of islets for 3 days to 200 U/ml of either IFN-gamma or TNF-alpha did not affect glucose-stimulated insulin release, but at higher concentrations (2000 U/ml) of either cytokine there was significant inhibition of glucose-stimulated insulin release.
484 3139756 At day 6, insulin content of the islets was significantly reduced by exposure to TNF-alpha but not IFN-gamma.
485 3139756 The synergistic functional and cytotoxic effects of IFN-gamma and TNF-alpha are consistent with a direct role for these cytokines in the destruction of beta-cells in insulin-dependent diabetes.
486 2903616 These studies therefore indicate that the GH suppressing hormone somatostatin may be of clinical value as an adjunct to insulin in the treatment of patients with insulin-dependent diabetes mellitus and labile blood glucose control.
487 2903837 Anterograde infusion of 500 pg/ml glucagon caused a larger increase in insulin secretion (245 +/- 10%) than retrograde infusion (45 +/- 4%), whereas somatostatin was stimulated more retrogradely (339 +/- 17%) than anterogradely (121 +/- 9%).
488 2903837 Anterograde infusion of somatostatin produced a larger decrease in insulin and glucagon than did retrograde perfusion (P less than .0001 for both comparisons).
489 3053303 After 9 days of treatment, insulin binding to adipocyte plasma membranes from both CS-045-treated Zucker fatty rats and KK mice was increased.
490 3053948 We studied the ability of bovine insulin, porcine insulin, and human insulin ICs to stimulate the procoagulant activity (PCA) of human blood monocytes (HBMs) and human umbilical vein endothelium (HUVE) in vitro.
491 3053948 For four different antibodies, the ratios of PCA (expressed by HBMs exposed to ICs or to antibodies alone and normalized for cell numbers) to activity expressed by tissue culture medium were as follows: beef insulin ICs, 2.55 +/- 0.41; por insulin ICs, 1.47 +/- 0.16; human insulin ICs, 1.28 +/- 0.19; and antibody, 1.28 +/- 0.32.
492 3053948 For a sixth antibody, HBMs could express PCA when stimulated with antibody of a relatively low binding capacity (0.35 ng bovine insulin per microgram of antibody) only in the presence of lymphocytes.
493 3053948 These observations raise the possibility that insulin ICs, that is, beef insulin ICs, may generate increased PCA and thereby contribute to the vascular complications of diabetes mellitus.
494 3053958 Insulin can regulate IGF-I production, acting on the GH receptor or at a post-receptor site.
495 3053958 Conversely IGF-I is thought to have a permissive effect on the pancreatic insulin response to glucose.
496 3054347 The requirements of insulin were reduced (p less than 0.001) during the course of the study, whereas the levels of glycosylated hemoglobin (HbA1c) and glucose were not changed.
497 3054430 These results suggest that insulin secretion of non-insulin-dependent diabetes mellitus (NIDDM) rat model is selectively impaired in response to glucose stimulation, possibly due to a disorder of signaling mechanism other than adenylate cyclase.
498 3056401 Insulin treatment (2 h) restored guanine nucleotide exchange factor activity to control values in both muscles.
499 3056401 Also, insulin treatment did not increase guanine nucleotide exchange factor activity in extracts from soleus and heart.
500 3183302 In 19 insulin-dependent diabetic patients (12 men and 7 women), RP induced cortisol release in all cases, GH and PRL release in men, but not in women, and no modification of LH and glucagon plasma levels; in 12 similar patients receiving saline infusions without RP, no endocrine modifications were observed.
501 3192039 In this study, we observed that LDL isolated from patients with insulin-dependent diabetes mellitus (IDDM) enhanced thrombin-induced platelet aggregation to a greater extent than LDL isolated from matched controls (P less than .01).
502 2461657 Anterograde infusion of insulin antibody increased glucagon and somatostatin secretion (p less than 0.0005), whereas retrograde insulin antibody infusion was without effect.
503 2461657 In contrast, retrograde infusion of somatostatin antibody increased both insulin and glucagon secretion (p less than 0.0005).
504 2461657 In comparison, anterograde infusion of antiglucagon antibody decreased somatostatin secretion without influencing insulin, whereas retrograde antiglucagon antibody infusion decreased insulin without changing somatostatin secretion.
505 2848176 Adipose tissue lipoprotein lipase activity of fed and fasted normal and diabetic sand rats correlated negatively with plasma insulin and glucose levels.
506 3057329 Increasing doses of Bay 1099 were found to decrease the postprandial rise in serum glucose concentration, delay the time to peak insulin concentration, and decrease the output of GIP after the meal.
507 3057484 Comparative analysis of indices during OGTT and food intake has shown that an increase in the levels of gastrin in patients with diabetes mellitus, type II, does not correlate with body mass and the total level of insulin, but it may correlate with a metabolically active form of insulin.
508 3058800 Inasmuch as DP bone marrow can transfer the susceptibility for diabetes to irradiated recipients, our present results suggest that an important predisposing factor for insulin-dependent diabetes mellitus in DP rats is the inability of DP prothymocytes to generate RT6+ T cells.
509 2850132 Glomerular filtration rate (GFR) (thalamate clearance), renal plasma flow (RPF) (hippuran clearance), and urinary albumin excretion rate (AER) were measured in 10 normoalbuminuric, normotensive insulin-dependent diabetic patients and 8 normal subjects before and during acute angiotensin converting enzyme (ACE) inhibition by means of enalapril (10 mg IV).
510 2905942 During the study endogenous insulin secretion was suppressed by somatostatin (300 micrograms h-1) and replaced by infusion of insulin (0.2 mU kg-1 min-1).
511 3063265 Severely hyperlipidemic alloxan-diabetic cholesterol-fed rabbits were treated with different daily doses of insulin in order to study the effect of insulin on plasma lipids, lipoproteins and postheparin lipoprotein lipase activity.
512 3063486 The angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce intraglomerular pressure in animal studies, and the use of these drugs to treat insulin-dependent diabetics with hypertension has produced a reduction in the rate of decline of glomerular filtration rate.
513 3063593 Insulin incubation in bathing medium for 4-5 hr enhances the decreased gastro-intestinal responses to sal, but not to 5-HT. 4.
514 3065196 Tolbutamide significantly decreased fasting plasma gastrin after 5 min of intravenous infusion in patients with atrophic gastritis, duodenal ulcer, or insulin-dependent diabetes mellitus (IDDM) as well as in healthy volunteers.
515 3066348 In conclusion: (1) the data show that AlCl3, probably through activation of a pertussis-toxin-inhibitable G protein, and PLC are able to modulate the intrinsic glucose carrier activity; (2) as pertussis toxin did not modify the effect of insulin, it seems unlikely that the insulin signal on glucose transport involves activation of this specific G protein.
516 3223190 In order to evaluate if in insulin-dependent diabetes lipid and apolipoprotein levels are differently affected by metabolic control in men and women, we measured the concentrations of fasting plasma glucose, mean plasma glucose, glycosylated hemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and apolipoproteins A and B in 94 sex matched patients.
517 2976300 Stearic acid delta 9 desaturase activity is drastically depressed in the BB rats when fatty acid composition of liver phospholipids and microsomal total liver lipids are changed in spite of the daily injection of insulin necessary for the BB rats survival.
518 3066563 IL-1 alpha inhibited both replication and insulin secretion and decreased the insulin content of both islets.
519 3067001 The increased insulin responsiveness of R rats was not due to an increase in insulin binding or to a decrease in insulin degradation (measured with intact cells or as cytosolic insulinase activity).
520 3069282 Increased SAA-concentrations did not correlate with sex or age of patients, diabetes duration, diabetes type, duration of pump treatment, route of insulin, insulin preparation, catheter material and pump model, indicating that pump treatment does not stimulate a specific amyloidogenic reaction.
521 3069766 The progression of metabolic events from hyperinsulinemia to NIDDM in monkeys includes cellular changes in insulin responses at the level of the adipocyte.
522 3071362 In the present study we have further analysed the effect of recombinant human interleukin-1 beta (rIL-1) on the biosynthesis and conversion of proinsulin 1 and 2 in rat islets.
523 3071362 During the 3 h labelling period the labelled proinsulin content compared to insulin was increased from 9.0 +/- 1.3% (control) to 26.6 +/- 6.4% in the IL-1 exposed islets, and the ratio between labelled insulin 1 to 2 was increased from 2.0 +/- 0.1 to 3.4 +/- 0.4, respectively.
524 3071395 On the other hand, the PTH-sensitive renal adenylate cyclase activity was significantly higher in short-term diabetic rats than in control and insulin-treated rats.
525 3149191 Associations of insulin dependent diabetes mellitus exist with the HLA-DR antigens DR3 and DR4 in both British Caucasoid and Dravidian subjects.
526 3230579 An increase in the capacity of serum IgG to bind to native type IV collagen was observed in patients with both insulin-dependent and non insulin-dependent diabetes mellitus.
527 3238312 However, patients who were HLA-DR3/DR4 heterozygotes and had diabetic neuropathy responded to insulin antigens more often by proliferation than DR3/DR4 positive patients without diabetic neuropathy.
528 3149924 The roles of protein kinase C, calcium and calmodulin in mediating insulin-stimulated lipogenesis by rat adipocytes were investigated using the protein kinase C activator, phorbol myristate acetate (PMA); the protein kinase C inhibitors, H7 and polymixin B; the calcium ionophore, A23187; the calcium channel blocker, verapamil; and the calmodulin inhibitor, calmidazolium.
529 3248365 IGF-I levels were determined by radioimmunoassay in 81 insulin dependent adolescent diabetics (49 boys and 32 girls) and compared with 75 puberty stage matched normal controls.
530 2521209 We studied the growth effects of insulin and IGF-I as measured by stimulation of c-myc, DNA synthesis, and cellular proliferation in the presence and absence of these antibodies.
531 2535823 Results showed that significant activation of the insulin-receptor kinase occurred after exposure in vivo to mean serum insulin concentrations as low as 34 +/- 3.5 microU/ml and that maximal activation was achieved by insulin levels less than or equal to 2000 microU/ml.
532 2642488 This treatment resulted in no change in 24-h glucose profiles, although the mean insulin dose decreased by 19%, while hemoglobin A1c decreased significantly (0.084 +/- 0.023 to 0.067 +/- 0.011, P = 0.04).
533 2643309 Microalbuminuria in insulin-dependent diabetics appears to indicate early renal damage rather than susceptibility to it, yet a series of relatively small, short-term intervention studies in insulin-dependent diabetes mellitus patients have already demonstrated reduction in albumin excretion rates or arrest in the increase of fractional clearance of albumin.
534 2643334 One-day insulin treatment increased PWAT weight and adipocyte size without stimulating mitoses.
535 2643334 The results demonstrate that 1) insulin is able to stimulate cell proliferation in PWAT of adult diabetic rats, 2) it transiently stimulates proliferative activity in adipose tissue after a 2- to 3-day period of induction, 3) the increase in adipocyte size precedes the enhancement of mitotic activity, and 4) the effects of insulin were specific, as in the same rats, under the same experimental conditions, insulin did not increase the cell labeling in brown adipose tissue.
536 2464510 The BB rat spontaneously develops insulin-dependent diabetes mellitus (IDDM) as an autoimmune abnormality involving the class II molecules of the major histocompatibility complex (MHC).
537 2563840 The release of tissue plasminogen activator (tPA) by vascular endothelial cells during exercise was studied in forty men with insulin-dependent diabetes.
538 2563840 These findings suggest that insulin-dependent diabetic patients with only slightly raised urinary albumin excretion have general endothelial cell dysfunction or damage.
539 2647487 Production of milk proteins can be induced in vitro by the synergistic interactions of prolactin, insulin, and glucocorticoids and is inhibited by EGF and progesterone.
540 2918051 During pirenzepine administration, hemoglobin A1c significantly decreased (P less than 0.02), and 4 of the 13 patients had lower daily insulin requirements (5-23 U/day), but there was no significant change for the group as a whole.
541 2918840 Multivariate analyses show that sex, age, body mass index, previous androgen and corticosteroid therapy, previous blood transfusion, initial hemoglobin and white blood cell and serum ferritin concentrations were not significantly related to hyperinsulinemia as expressed by the integrated insulin area under the curve of glucose tolerance test.
542 2919156 Fructosamine and various measures of blood glucose were compared to glycosylated hemoglobin as indices of glycaemic control in 148 patients with insulin treated diabetes.
543 2921565 The study group presented the HLA characteristics known to occur in insulin-dependent diabetes: increase in A30, B8, B18, D6, DR3, DR4, BfF1 and decrease in A3, B7, DR2.
544 2495077 To determine whether insulin dependent diabetics with microalbuminuria have significant abnormalities in concentrations of lipoproteins, apolipoproteins AI and B, fibrinogen, and clotting factor VII which could result in increased cardiovascular risk.
545 2523783 GST B1 concentrations were significantly increased 3 h after controlled insulin-induced hypoglycaemia, both in the diabetic patients (p less than 0.02) and in the normal group (p less than 0.05), but the magnitude of the rise did not differ between these two groups.
546 2523787 A complementary in vitro study using adipocytes from non-obese healthy volunteers failed to show any direct effect of metformin on adipocyte insulin binding or glucose transport and metabolism, at media drug concentrations corresponding to therapeutic plasma levels.
547 2540178 Insulin and insulin-like growth factors (IGF-I and IGF-II) in the presence and absence of GTP gamma S did not stimulate PIP2-PLC or PI-PLC in plasma membranes and cytosol preparations nor phosphoinositide breakdown in isolated human hepatocytes.
548 2653258 The symptoms of this biochemical abnormality, the pathophysiology of which is not yet clearly understood, are the following: lack of clinical manifestations, except for a variable and intermittent glycosuria; constant abnormal glucose tolerance tests, above 97 percentiles of the reference value with some variations over time; normal immunoreactive insulin levels; percentage of glycosylated hemoglobin at the upper range of normal; dominant autosomal genetic transmission and no association with HLA markers like in insulin-dependent diabetes; lack of degenerative complications of the micro-angiopathic type, at least on these cases even after more than 30 years of follow-up; finally, no tendency towards insulin-dependent diabetes.
549 2703288 Previous data have indicated that decreased sex hormone binding globulin (SHBG) is associated with increased overall and upper body adiposity and higher levels of glucose, insulin and triglyceride (TG) and decreased levels of high-density lipoprotein (HDL) cholesterol.
550 2703526 In addition, TNF administration to diabetic animals leads to an elevation in serum glucose levels (73% at 17 h) without a change in serum insulin levels.
551 2541440 Protein kinase C agonists (phorbol ester and diacylglycerol) and agonist precursor (myoinositol) reversed the Na+ pump lesion, suggesting that protein kinase C-dependent phosphorylation of the 100-kDa subunit regulates Na+ pump activity and that insulin can influence erythrocyte protein kinase C activity.
552 2542108 The biological effects of insulin and IGF-I were examined by studying adipocyte lipoprotein lipase (LPL).
553 2542427 IGF-I and IGF-II as well as the low molecular type of IGF binding protein (IGFPB) were determined in serum from 11 adolescents with insulin-dependent diabetes mellitus (IDDM) during a cross-over study with conventional and continuous subcutaneous insulin infusion (CIT and CSII) therapy.
554 2542427 The findings of elevated IGF-II and IGFBP levels and correlations between IGFBP and blood glucose concentration as well as IGF-II and HbA1c levels in adolescents with IDDM indicate that both IGF-II and IGFBP reflect a deranged metabolism caused by inadequate insulin administration.
555 2653925 Treatment of pancreatic acini from diabetic rats with insulin resulted in a dose-dependent increase in the phosphorylation of ribosomal protein S6 when analyzed by two-dimensional gel electrophoresis.
556 2653925 The S6 kinase activated by insulin was highly specific for the ribosomal protein S6 when compared with various substrates, including casein, glycogen synthase, phosphorylase b, phosvitin, histone HIII-S, and histone HVIII-S.
557 2653935 To examine the causal relationship between IFN and insulin resistance, we injected natural human leukocyte IFN-alpha (3 x 10(6) IU, i.m.) twice overnight in eight healthy subjects and determined oral (OGT) and intravenous (IVGT) glucose tolerance and sensitivity to insulin (287 nmol or 40 mU.m-2.min-1 euglycemic insulin clamp) the following morning.
558 2655598 Islet amyloid polypeptide inhibited the glucose-stimulated insulin secretion from isolated rat pancreatic islets, as calcitonin gene-related peptide did, but the fragments failed to inhibit the secretion.
559 2656140 Insulin responsiveness was markedly elevated; the steady-state glucose infusion rate (SSGIR) of step 4 was 104 vs. 64 mumol.kg-1.min-1 (range 50-79) in controls and 61 mumol.kg-1.min-1 (range 47-69) in IDDM subjects.
560 2656140 In the patient with newly diagnosed IDDM, the initial marked increases of insulin action and clearance were due to coexistent hyperthyroidism.
561 2658456 Chronic insulin treatment of diabetic rats reversed the increase in somatostatin, but had no effect on the increase in insulin-like immunoreactivity concentration.
562 2471969 Administration of insulin (6 U/100 g/day) to normal Sprague-Dawley rats increased the activity of amylase as well as lipase and colipase, whereas injection of glucagon (0.3 mg/100 g/day) decreased the activity of amylase and colipase but had no significant effect on lipase activity.
563 2525915 Daily administration of insulin to the streptozotocin-induced diabetic mice increased the hepatic levels of EGF receptor messenger RNAs to almost normal levels.
564 2525915 These results indicate that EGF binding to its receptor decreases in the liver of diabetic mice, involving alterations in the level of EGF receptor messenger RNAs, and that insulin is important for the regulation of EGF receptor gene expression in the liver but not in the kidney.
565 2543360 The present experiments were designed to determine the effect of glucagon, cAMP [8-(chlorophenylthio) cyclic AMP], and insulin + cAMP on CPT transcription and mRNA amounts over time after injection.
566 2543360 The data indicate that glucagon and insulin interact in control of transcription rate and amount of CPT mRNA, but that increases in CPT immunoreactive protein and activity are temporally delayed.
567 2544091 Insulin also stimulated Vmax of both SDR and NDR by 50% at 5 minutes.
568 2544091 In contrast to control and both subgroups of the BB rat (SDR and NDR), insulin stimulated adipose tissue from STZ-DM less than 10% at 5 minutes.
569 2567260 However, we also used computer simulation to investigate how the insulin gene region could contribute susceptibility to IDDM without yielding evidence for distortion in insulin gene sharing in a sample comparable to that of GAW5.
570 2658981 The erythrocyte membrane acetylcholinesterase activity is significantly (P less than 0.001) decreased in insulin-dependent diabetes mellitus. 2.
571 2659052 In the eight years that have elapsed since the first implantation of an insulin pump in a human subject, insulin delivered by implantable pump has been shown to improve metabolic control while reducing total and LDL cholesterol, serum amyloid A, and serum anti-insulin antibody titres.
572 2661283 Hyperexpression of major histocompatibility complex (MHC) molecules by islet cells is a prominent, early feature of islet pathology in insulin-dependent diabetes mellitus and concomitant with beta-cell failure after exposure of islets to specific cytokines or viruses.
573 2662016 Insulin treatment of the streptozotocin-diabetic rats or refeeding the fasted animals causes a rapid recovery of the GLUT-4 mRNA to levels significantly above those observed in untreated control animals.
574 2662183 In addition, we determined that transcription of the glucokinase gene increased at least 20-fold when diabetic rats were treated with insulin for 2 hr.
575 2663078 Insulin action on regulation of hepatic malic enzyme has been investigated in comparison with fructose, using streptozotocin-induced diabetic rats.
576 2663078 On the other hand, by feeding a high-fructose diet to diabetic rats, the malic enzyme mRNA concentration was considerably increased, though with a delayed peaking in comparison with the insulin-treated animals, whereas the transcriptional rate was not significantly increased.
577 2663078 These results suggest that insulin is required in both the translational and transcriptional regulation of malic enzyme.
578 2663571 However, since insulin-mediated regulatory processes have been shown to be tissue specific, we decided to examine malic enzyme activity in the epididymal fat pads of normal, diabetic, and insulin-treated normal and diabetic rats.
579 2663571 Insulin treatment of both normal and diabetic rats resulted in an increase in epididymal fat pad malic enzyme activity due to increases in both enzyme quantity and specific activity.
580 2733941 Because magnesium deficiency may occur in insulin-dependent diabetic patients, mainly because of urinary magnesium losses, we hypothesized that serum parathyroid hormone and calcitriol do not increase in the diabetic pregnancy.
581 2502884 Experiments on rats using the primary monolayer culture of isolated islet cells proved that insulin secretion is directly modulated by the growth hormone (GH), C-terminal tetrapeptide of cholecystokinin, thyroliberin, and met-enkephalin, and by certain blood plasma factors of diabetes I patients.
582 2526137 While diabetic animals from both diet groups had similar elevated glycated hemoglobin levels and increased levels of nonenzymatic glycation of glomerular basement membrane, these were significantly elevated as compared to insulin treated diabetic (euglycemic), age-matched controls on an 8% protein diet, and streptozotocin injected nondiabetic animals from both diet groups.
583 2546940 The fetal receptor does not appear to bind insulin but, unlike the IGF-I receptor, its phosphorylation is stimulated by low physiological concentrations of both insulin and IGF I.
584 2547157 These data indicate that glucose and insulin can play independent roles in regulation of PEPCK gene expression, and that these regulatory effects are usually transient.
585 2568667 Changes in plasmatic levels and retinal content of somatostatin after insulin-induced hypoglycemia were investigated in three different groups of animals: Control group (C), Diabetic untreated group (D); and, Insulin-treated diabetic group (DI).
586 2665520 Whereas total cardiac glycogen phosphorylase activity appears to be unaffected by severe insulin deficiency, a diabetes-induced decreased in hepatic glycogen phosphorylase activity has been demonstrated by our laboratory and others using liver extracts, isolated perfused liver, and cultured hepatocytes.
587 2666064 Mean total hemoglobin A1 (HbA1) significantly (at least P less than 0.05) decreased while the plasma free insulin level significantly increased (at least P less than 0.05) under ICIT.
588 2666106 These combined observations suggest that exposure to IL-1 induces a preferential decrease in glucose-mediated insulin release and mitochondrial glucose metabolism.
589 2666202 The enzyme action on glucose transport was not due to a nonspecific membrane perturbation because neuraminidase caused only a nonsignificant decrease in the uptake of the amino acid analog alpha-(methylamino)isobutyric acid and had no effect on basal or insulin-stimulated protein synthesis.
590 2666202 Insulin binding was slightly increased in neuraminidase-treated cells, yet the shapes of the dose-response curves for insulin stimulation of glucose transport were similar (EC50 = 0.087 +/- 0.010 and 0.082 +/- 0.008 nM for control and treated cells, respectively).
591 2759363 In a previous study we demonstrated that the kidney content of somatomedin C was maximal one to two days after uninephrectomy or induction of diabetes, and that insulin treatment prevented an increase in kidney somatomedin C as well as kidney growth in diabetic animals.
592 2475378 The neuropeptide galanin inhibits glucose-stimulated insulin release in dogs and rodents and has been proposed as having a role in the control of insulin release in humans.
593 2475378 The results showed no effect of galanin infusion on plasma glucose or serum insulin, although a rise in serum growth hormone even in the face of the intravenous glucose load confirmed the potent growth hormone-stimulating effect of galanin.
594 2504638 Vigorous blood glucose control with insulin therapy was accompanied by a complete prevention of capillary basement membrane thickening in both capillary beds, whereas aldose reductase inhibitor treatment achieved a complete prevention of basement membrane thickening in the deep capillary bed but not in the superficial capillary bed of the diabetic retina.
595 2527700 The effects of strict metabolic control (multiple insulin injections for 1 week) on urinary albumin excretion, glomerular filtration rate and extracellular fluid volume was evaluated in long-term Type 1 diabetic patients with (n = 9) and without (n = 10) incipient nephropathy.
596 2527701 Alterations of hypothalamic neuropeptide Y, which has potent experimental effects on hypothalamo-pituitary function, may contribute to certain neuroendocrine disturbances in insulin-deficient diabetes.
597 2668761 Although increased production of IAPP may initially cause insulin resistance, prolonged overproduction of IAPP may ultimately impair insulin secretion by leading to the progressive deposition of insoluble islet amyloid, a finding apparent in most subjects with overt diabetes.
598 2761414 To assess the effect of experimentally induced insulin-dependent diabetes mellitus (IDDM) on total body lipid composition, homogenates of neonatal (0-day) and 6-day Sprague-Dawley rat pups treated on day 0 with 65 mg/kg body weight of streptozotocin (STZ) or citrate buffer alone were compared using thin-layer and gas-liquid chromatographic techniques.
599 2764926 An avian insulin-like growth factor I (IGF-I) activity from unfertilized chicken egg-yolk has been partially purified by HPLC.
600 2530249 Our data demonstrate that CD8+ T cells play an important role in controlling peripheral tolerance to insulin and may abrogate IIR in a diabetic patient treated with SBI.
601 2678583 Type 2 diabetic patients are known to frequently have a high insulin level and were recently described as having high plasminogen activator inhibitor (PAI) activity, compared to normal controls.
602 2678583 As we have shown in several clinical conditions (normal subjects, obese patients, angina pectoris patients) that plasma PAI activity was linked with plasma insulin, we have studied in 38 type 2 diabetic patients the relationship between PAI activity, insulin and other parameters.
603 2678583 A significant correlation was found between PAI activity and insulin (r = 0.60, p less than 0.001), body mass index (r = 0.32, p less than 0.05) and Apolipoprotein B (r = 0.33, p less than 0.05).
604 2680233 It is concluded that endogenous insulin secretion (assessed by C-peptide concentration) is relatively unimportant in modifying HDL metabolism in IDDM and that associated clinical features, in particular ambient hypertriglyceridaemia, are of greater importance.
605 2681500 We conclude that the diabetic rat is not a good model to study growth stimulation by short-term insulin or IGF-I treatments because the insulin-like effects of these peptides obscure their specific growth-promoting activities in this model.
606 2681900 Then HDL 2-cholesterol/HDL 3-cholesterol ratio was significantly increased from 4.8 to 5.1 (p less than 0.001) in insulin group. 4) LCAT activity were significantly decreased from 790 to 637 (nmol/ml.h) (p less than 0.05) in insulin group, but did not change in other two groups.
607 2681900 In conclusion, compared to diet alone and sulfonylurea groups, insulin group made significant reduction of HDL 3-cholesterol and LCAT activity during hospitalization.
608 2805586 Products of the pro-opiomelanocortin gene have been shown to have marked effects on insulin secretion.
609 2805586 Selective antagonists of beta-endorphin have been reported to correct the impaired insulin secretory response to glucose seen in non-insulin dependent diabetes.
610 2531549 Likewise, raising perfusate glucose levels to 400 mg/dl or adding insulin (180 microU/ml) to the perfusate failed to modify responses to ANG II.
611 2555241 Considered together, the presence of CRBP and CRABP in a beta-cell line and the increase in KCl-induced insulin release by retinol and retinoic acid are consistent with the idea that retinol has a functional role in insulin secretion and suggest a potential mechanism of action at the beta-cell level similar to that observed in other retinoid-responsive cells.
612 2555679 Alloxan diabetes induced in white rats by intraperitoneal injection of alloxan-monohydrate (15 mg/100 g body weight) was used to study changes in the glycogen phosphorylase a and b, phosphoprotein phosphatases and hexokinase activities under insulin deficiency conditions.
613 2573522 Insulin binds to a receptor on the cell surface, thereby triggering a biological response within the target cell.
614 2573554 Seven nondiabetic and seven IDDM subjects were studied with the pancreatic clamp technique to control plasma insulin, growth hormone, and glucagon concentrations at the desired levels.
615 2573554 We conclude that adipose tissue lipolysis is normally exquisitely sensitive to insulin and that sensitivity, but not responsiveness to insulin, is impaired in poorly controlled IDDM.
616 2481706 In this study the effect of insulin and changes in the glucose concentration on in-vitro IGFBP-1 secretion by the Hep G2 cell line was studied.
617 2481706 Insulin suppressed IGFBP-1 secretion maximally at 100 mU/l (-32%) within 6 h.
618 2481706 The findings in the Hep G2 cell line that a variation in the physiological concentrations of glucose and insulin each independently regulate IGFBP-1 secretion suggest that this cell line may be a suitable model for further in-vitro studies of the regulation of secretion of IGFBP-1.
619 2532536 The present prospective follow-up study was made to study the effect of glycaemic regulation on levels of factor VII, protein C and protein S in 15 insulin-dependent diabetic patients without manifestations of vascular disease.
620 2606746 In Caucasoids HLA-DQB1 genes encoding amino acids other than aspartic acid at position 57 of the DQ beta chain (non-Asp-57) are associated with susceptibility to develop insulin-dependent diabetes mellitus (IDDM), while resistance is associated with aspartic acid at this residue (Asp-57).
621 2608374 Clinical and laboratory studies into the physiochemical properties of circulating immune complexes, serum IgA, IgM, IgG and antibodies against insulin contained by blood serum and circulating immune complexes were conducted in 102 children aged 7-14 years.
622 2689074 Sorbitol dehydrogenase activity in blood was increased similarly in normal, diabetic and insulin-treated diabetic mice after CCl4 administration. 7.
623 2690958 In normal metabolism, amylin could act in concert with insulin as a signal for the body to switch the site of carbohydrate disposal from glycogen to longer-term stores in adipose tissue, by making skeletal muscle relatively insulin-resistant, whilst at the same time leaving rates of insulin-stimulated carbohydrate metabolism in adipose tissue unaltered.
624 2690958 As patients with insulin-treated IDDM frequently experience problems with hypoglycaemia, and as amylin acts to modulate the action of insulin in various tissues, it is possible that amylin deficiency may contribute to morbidity in insulin-treated IDDM, perhaps through the loss of a natural damping mechanism which guards against hypoglycaemia under conditions of normal physiology.
625 2691218 However, glucose-stimulated insulin release was significantly impaired after 3 days of in vivo administration of IL-1, either 3 micrograms/animal/day or 0.3 micrograms/animal/day.
626 2691218 The administration of IL-1 inhibited an acute phase of glucose-induced insulin release, whereas neither basal insulin secretion nor insulin release from 10-30 min of perifusion with glucose was impaired.
627 2691880 The ability of TSH to increase thyroglobulin, but not thyroid peroxidase mRNA levels, requires insulin, 5% serum, or insulin-like growth factor-I.
628 2691880 Insulin or insulin-like growth factor-I alone can increase thyroglobulin mRNA levels as well as or better than TSH but have only a small effect on thyroid peroxidase mRNA levels by comparison to TSH.
629 2612759 When pancreatic mRNA was analysed, a 16-fold elevation in islet amyloid polypeptide mRNA was observed with only a four-fold increase in insulin mRNA levels.
630 2692945 Insulin might overcome the glucose effect by activating pyruvate kinase through the known mechanism of enzyme dephosphorylation.
631 2695283 The prevalence of insulin-dependent diabetes in BB rats was increased in the IAP group as compared to controls.
632 2695369 We also suggest that in the presence of defective proinsulin processing and insulin release, as occurs in NIDDM, hyperglycemia stimulates amylin biosynthesis so that this peptide is deposited in increased quantities in the islet as amyloid.
633 2485904 The effect of cholecystokinin (CCK-33) and its fragments, C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4), on arterial blood pressure and on the function of the isolated rat heart was studied in three groups of animals: normal (C group), rats with streptozotocin-induced diabetes of one month's duration (DM group) and with diabetes treated with insulin (DMI group).
634 2517027 Insulin-dependent diabetes mellitus (IDDM, type I) is an autoimmune disorder exhibiting a strong association with particular haplotypes of the major histocompatibility complex (MHC).
635 2518361 When tested as single agents or added together at very low concentrations, interleukin 1 (IL-1), tumor necrosis factor (TNF), and interferon gamma (IFN-gamma) inhibited insulin release from rat islet cell monolayer cultures during 4 day incubations; however, this secretory function improved after the cytokines were removed.
636 2518361 In contrast, combinations of slightly higher concentrations of IL-1, TNF, and IFN-gamma produced irreversible inhibition of insulin release, as well as decreased cell insulin content and proportional increase in cell lysis, measured as release of 51Cr from labeled islet cell cultures.
637 2518361 These findings suggest that cytokine products of T lymphocytes (IFN-gamma) and macrophage/monocytic cells (IL-1, TNF) infiltrating pancreatic islets in "autoimmune" diabetes may interact synergistically to produce functional inhibition or lethal cytocidal effects on islet beta-cells, possibly accounting for reversible and irreversible stages of insulin-dependent diabetes.
638 2534889 Changes were determined in the activity of submandibular gland N-acetyl-beta-glucosaminidase from streptozotocin-induced diabetic and insulin-treated rats.
639 2534889 It is clear from these findings that the diabetic condition brings about an insulin-dependent increase in the activity of N-acetyl-beta-glucosaminidase in the rat submandibular gland, and imparts certain changes in the properties of the enzymatic proteins themselves.
640 2698436 We have studied the comitogenic activity of IL 1 produced by cultures of mononuclear adherent cells obtained from Diabetes Mellitus (DM) type II or non insulin dependent diabetic patients.
641 1967178 However, insulin infusion at doses that normalized the portal insulin concentration (approximately 208 pmol/L) together with glucagon replacement inhibited the rise in glucose production in both normal and IDDM subjects.
642 2403453 The nonglycosylated form of PRL may play a role in B-cell function by promoting protein synthesis, which results in augmented insulin synthesis.
643 2403617 Injection of heparin to stimulate the action of lipoprotein lipase increased the removal rates in both control and insulin-deficient rats, but control values were not restored by heparin given to insulin-deficient rats and compared with controls the difference due to insulin deficiency persisted.
644 2403617 Compared with control rat plasma, more of apolipoproteins AI and AIV and less of apolipoprotein E isoforms associated with emulsions exposed to insulin-deficient rat plasma.
645 2404722 In patients, total-body insulin-mediated glucose metabolism correlated with the degree of glycemic control as assessed by the level of glycosylated hemoglobin (r = -0.63, P less than 0.001).
646 2404746 When islets were cultured for 18 h only, also 5000 pg/ml IL-6 stimulated the medium insulin accumulation.
647 2404746 IL-6 did not affect the islet insulin content and the rates of islet (pro)insulin and total protein biosynthesis.
648 2404746 In short-term experiments after 48-h culture with IL-6, there was a dose-dependent inhibition of the glucose-stimulated insulin release.
649 2491258 Recent studies have also shown that both amylin and CGRP are potent inhibitors of insulin-stimulated glycogen synthesis in skeletal muscle in vitro.
650 2491643 Thus, patients with IDDM of recent onset and diagnosed within the last three years more frequently responded to insulin by proliferation and less often had HLA-DR3 than patients with IDDM of long duration and diagnosed about 20-25 years earlier.
651 2137789 In the short-term, IL-1 beta induced a dosage-dependent stimulation of insulin release.
652 2137801 Subcutaneous insulin infusion, resulting in circulating plasma free-insulin levels in normotensive control subjects comparable to those in IDDM patients, inhibited natriuresis, increased proximal tubule sodium reabsorption at the level of the kidney, and inhibited an adequate ANP stimulation by saline challenge.
653 2179271 Treatment with a borderline diabetogenic dose of streptozotocin reduced amylin response without significantly changing the insulin response.
654 2407478 In L6 muscle cells in culture, acute treatment (1 h) with insulin causes recruitment of glucose transporters to the plasma membrane, and prolonged exposure to insulin or to glucose-deprived medium causes increased expression of GLUT-1 mRNA and GLUT-1 protein.
655 2407519 However, it has recently been observed that when IGF-I is infused into man and animals, plasma insulin levels fall, raising the possibility that IGF-I may also be an inhibitor of insulin secretion.
656 2407519 This study used the in vitro perfused rat pancreas and recombinant human IGF-I and IGF-II to determine if either of these peptides affected insulin and/or glucagon secretion from normal rats.
657 2407519 IGF-I given with 7.8 mM glucose suppressed insulin secretion by as much as 65%, with the half-maximal effect occurring at less than 10 ng/ml.
658 2407519 IGF-II (200 ng/ml) also suppressed insulin release, but the effect was less pronounced than for IGF-I and was present at 16.7 mM glucose, but not at 7.8 mM glucose.
659 2407519 We conclude from these results that 1) IGF-I at physiological concentrations is a potent inhibitor of both glucose- and arginine-induced insulin secretion; 2) the magnitude of the inhibition depends on the background glucose concentration; and 3) the inhibition fully reverses when IGF-I is stopped.
660 2407519 These results support an in vivo effect of IGF-I to modulate insulin output.
661 2407583 This model prevented variations in insulin secretion induced by IGF-I and permitted evaluation of the effects of IGF-I on extrapancreatic glucagon.
662 2407583 This was continued throughout the experiment, allowing evaluation of IGF-I effects on insulin clearance.
663 2407583 The insulin dose required to induce the same plasma glucose decline as IGF-I (44 +/- 6 vs. 43 +/- 5%, NS) was 9-12 times lower (0.06-nmol/kg bolus + 6.4 +/- 0.6 pmol.kg-1.min-1).
664 1970540 We determined islet amyloid polypeptide (IAPP) response in plasma to oral and intravenous glucose administration and intravenous insulin injection in nondiabetic subjects.
665 1971774 These results indicate that glucose and insulin may play a role in the regulation of GHRH release following a mixed meal but circulating levels of GHRH and SMS are unlikely to be relevant to the abnormal regulation of GH in IDDM.
666 2111887 GnRH-stimulated serum LH levels were higher in diabetic vs. control and diabetic insulin-treated animals.
667 2135382 These findings support the hypothesis that stiff-man syndrome is an autoimmune disease and suggest that GAD is the primary autoantigen involved in stiff-man syndrome and the associated insulin-dependent diabetes mellitus.
668 2140181 Urinary (CPU) and plasma C peptide values at baseline (CP0) and under stimulation with glucagon were determined in healthy subjects (n = 17) and in insulin-dependent (IDD, n = 45) and non insulin-dependent (NIDD, n = 32) diabetics.
669 2140801 We also investigated the role of insulin in regulation of IGF-I expression in the aorta.
670 2140801 In nondiabetic rats, administration of insulin as an acute bolus (10 U i.p.) or a chronic infusion (2.4 U/day for 5 days) resulted in an approximately twofold increase in abundance of IGF-I mRNA in the aorta.
671 2159998 To determine the effects of an aldose reductase inhibitor (ARI) on diabetes-induced cardiac autonomic nerves disturbance, we examined the effects of ONO-2235, an ARI, as well as insulin on the responsiveness to the nerve stimulation and agonists of the isolated atria of the streptozotocin-induced diabetic rats.
672 2185104 Expression of this enzyme is differentially regulated; hepatic glucokinase is stimulated by insulin and repressed by cAMP, whereas beta-cell glucokinase activity is increased by glucose.
673 2187189 In contrast to insulin, this effect of IGF-I occurs despite persisting hyperglycemia and adrenal hyperplasia.
674 2187662 Though this study does not prove a causal relationship between restoration of ovarian function and normalization of circulating IGF-I levels, a relationship has been established, as evidenced by higher levels of IGF-I in both the control and insulin-treated diabetic proestrous groups when compared to the diestrus groups.
675 2188117 Expression of a mutant INSR cDNA with a deletion of the region corresponding to exon 2 of the INSR gene produces a protein devoid of insulin-binding activity, although the mutant protein is processed appropriately to alpha- and beta-subunits, suggesting that the insulin-binding domain is encoded at least in part by exon 2.
676 2188897 Elevated serum angiotensin converting enzyme activity and plasma renin activity, expressed as generated angiotensin I, were unaffected by the lower dose of insulin, but were reduced by 26% and 40%, respectively at the higher dose.
677 2189759 Glucokinase explains the capacity, hexose specificity, affinities, sigmoidicity, and anomeric preference of pancreatic islet glycolysis, and because stimulation of glucose metabolism is a prerequisite of glucose stimulation of insulin release, glucokinase also explains many characteristics of this beta-cell function.
678 2189762 Only very high concentrations of CCK-8 (15 micrograms.kg-1.20 min-1) produced a small increase in plasma insulin levels, indicating a strong CCK-8-eliminating mechanism in the liver.
679 2189828 Red cell phosphoglycerate kinase (PGK) activity was determined in normal individuals and patients with, type I (insulin-dependent) diabetes and insulin treated diabetes.
680 2332119 We examined insulin binding, insulin-stimulated autophosphorylation, and phosphorylation of poly(Glu.Na,Tyr)4:1 by liver and skeletal muscle insulin receptor from lean, obese, and obese streptozocin-induced diabetic Zucker rats.
681 2332631 In contrast, low dose IL-1 beta (0.5 microgram/kg) administration significantly reduced the frequency of insulin-dependent diabetes mellitus (48%) compared to placebo (86%) and high dose IL-1 beta (93%) treatment groups.
682 2333960 In conclusion, 1) at rest, myocardial lactate and amino acid uptake is markedly impaired in IDDM without coronary artery disease, and 2) the metabolic abnormalities of the diabetic myocardium are not a primary phenomenon but rather a consequence of hypoinsulinemia and hyperglycemia because insulin administration, resulting in euglycemia, restored normal patterns of cardiac metabolism.
683 2113530 The present study was designed to determine if diet fat-induced alteration in the fatty acid composition of the adipocyte plasma membrane alters insulin binding and the insulin responsiveness of glucose metabolism in control and diabetic states.
684 2189884 Results of the application of this protocol in IDDM were consistent with previous observations that insulin sensitivity is reduced in poorly controlled IDDM and normalized in well controlled patients.
685 2190214 After 12 days (glucose at 54 +/- 8 mg/dl), GLUT-2 mRNA signal density was undetectable whereas proinsulin mRNA was reduced by 51%.
686 2190214 Hyperglycemic clamping increased GLUT-2 mRNA by 46% (P = 0.001) whereas proinsulin mRNA doubled (P = 0.001).
687 2190782 Immunoglobulin fractions negative for ICSA either from four patients with recently diagnosed IDDM or from four newly diagnosed NIDDM patients had only negligible effect on insulin release after stimulation with glucose.
688 2192715 Pioglitazone also corrected the abnormality in hepatic enzyme regulation by insulin of the fatty rats: glucose-6-phosphatase decreased and glucokinase increased, suggesting the increased response of the liver to insulin and the resultant suppression of HGP.
689 2354749 Because a central feature of non-insulin-dependent diabetes mellitus (NIDDM) is an imparied ability of insulin to enhance glucose disposal in skeletal muscle, we examined the hypothesis that reduced expression of GLUT4 is a characteristic finding in the skeletal muscle of subjects with NIDDM.
690 1695314 Therefore, the effects of isradipine, a new calcium antagonist, on glucose tolerance and insulin secretion during a 75-g oral glucose tolerance test (OGTT) and on ADP- and collagen-induced maximum first-wave platelet aggregation (Tmax%) were studied in 11 type II diabetic patients with borderline hypertension.
691 1695481 The addition of 200 microU/ml of insulin in the incubation media did not change the TRH-stimulated TSH release, but it decreased the basal TSH release by 42%.
692 1695481 In the same experimental conditions, no effect of insulin or glucose was seen on the basal or TRH-stimulated TSH release from thyrotrophs of diabetic rats.
693 1695589 Pig galanin inhibited the insulin output elicited by arginine (approximately 45%, P less than 0.05) but did not affect the somatostatin and glucagon responses to the aminogenic stimulus.
694 2115042 Interleukin-1 (IL-1), tumor necrosis factor (TNF), and interferon-gamma (IFN gamma) inhibit insulin release and may be cytotoxic to isolated rodent pancreatic islets.
695 2115042 Assay of insulin and glucagon in the islet monolayers revealed that IL-1, TNF, and IFN gamma inhibited both B- and A-cell secretory functions; however, only IL-1 and TNF produced permanent decreases in insulin and glucagon contents in the islet cultures.
696 2164373 All groups that received insulin had lower collagenase activity than both controls and diabetic rats that received EGF.
697 2164373 The individual effects of insulin and EGF added synergistically for a net gain in wound collagen content after 15 days.
698 2164920 We recently identified a 32 K mol wt insulin-like growth factor (IGF)-binding protein (BP) which is markedly increased in the serum of streptozotocin-diabetic rats and recognized by antiserum against the human amniotic fluid IGFBP (hIGFBP-1).
699 2197139 These results suggest that prophylactic insulin therapy to prevent IDDM in humans should be considered for clinical trials.
700 2198187 Islet amyloid in diabetic Pima Indians may indicate a primary Beta-cell defect which interacts with insulin resistance to produce diabetes, or may develop as a result of Beta-cell dysfunction induced by insulin resistance and hyperglycaemia.
701 2199215 In the short-term (1 h), 25 U/ml IL-1 beta significantly increased the rates of insulin release and glucose utilisation, but not glucose oxidation.
702 1974524 To examine the effects of growth hormone-releasing factor (GRF) on islet hormone release, rat pancreas was perfused. rhGRF at the concentration of 10(-7) M or more enhanced insulin secretion stimulated by 16.7 mM glucose, hpGRF slightly enhanced insulin secretion as well.
703 1975377 Binding of M tuberculosis heat-shock protein 65 antibodies to interleukin-1 beta-treated cells was inhibited by prior addition of serum from insulin-dependent diabetic patients which contained antibodies to 64 kD beta-cell antigen.
704 2118234 We have previously reported the induction of diabetes in transgenic mice (ins-IFN-gamma) in which the expression of the lymphokine IFN-gamma is directed by the insulin promoter.
705 2200528 FGF responses were abolished, EGF responses were partially inhibited, whereas the response to insulin was unaffected.
706 2201540 Two 8-h primed continuous infusions of L-[1-13C] leucine were used to determine fractional synthesis rates of albumin and non-albumin plasma protein in post-absorptive Type I diabetic patients during insulin infusion and its withdrawal.
707 2203761 Cells expressing the normal human receptor were 10-fold more sensitive to insulin than the untransfected CHO cells with respect to phosphorylation of a cellular substrate (pp 185) on tyrosyl residues, glucose incorporation into glycogen, thymidine incorporation into DNA, and phosphorylation of ribosomal protein S6.
708 2384663 We previously reported that streptococcal preparation (OK-432), which is a TNF inducer, inhibits insulitis and development of autoimmune diabetes in nonobese diabetic (NOD) mice and Bio-Breeding (BB) rats, as animal models of insulin-dependent diabetes mellitus.
709 2392901 The urinary excretion of albumin (a marker of glomerular damage) and retinol binding protein (a low molecular weight protein marker of tubular dysfunction) was determined by sensitive immunochemical methods in 110 insulin-dependent (Type I) diabetic patients.
710 1698582 To investigate the target antigen(s) recognized during the autoimmune process in insulin-dependent diabetes mellitus (IDDM), we produced human monoclonal antibodies by Epstein-Barr virus transformation of peripheral blood lymphocytes from a large number (n = 50) of newly diagnosed IDDM patients.
711 1698676 GH infusion resulted in a similar meal-induced fall in IGFBP-1 levels but led to a delayed nocturnal rise in IGFBP-1, which was associated with elevated postprandial insulin concentrations.
712 1976213 Originally characterized as a hypothalamic regulator of growth hormone secretion, somatostatin also regulates the secretion of several other pituitary, pancreatic, and gastrointestinal (GI) hormones including thyrotropin-stimulating hormone, insulin, glucagon, and gastrin.
713 1976221 Somatostatin secreted by pancreatic D cells is a potent inhibitor of insulin, glucagon and growth hormone secretion, as well as other cells.
714 2145090 Cardiac ANP synthesis in the diabetic rats completely reverted to control levels after insulin therapy, accompanied by normalization of hemodynamic parameters.
715 2168718 Cytochrome P-450 content of both normal and diabetic cells was not affected by insulin in absence or presence of phenobarbital.
716 2204154 Amylin, a novel pancreatic hormone, secreted along with insulin from the pancreatic beta-cells, can modulate insulin effects, to produce insulin resistance in skeletal muscle and liver.
717 2204623 These data show that the juxtamembrane region of the insulin receptor contains residues essential for insulin-stimulated internalization and suggest that the sequence NPXY [corrected] may play a general role in directing the internalization of cell surface receptors.
718 2210059 The effect of insulin on plasma amino acid concentrations and leucine metabolism was examined in 18 healthy nondiabetic young volunteers and in 7 subjects with insulin-dependent diabetes mellitus (IDDM) with the euglycemic insulin-clamp technique (40 mU.m-2.min-1) in combination with [1-14C]leucine.
719 2210070 This conclusion supports the view that glucokinase is a key enzyme in the recognition of glucose as an insulin secretagogue in pancreatic islets.
720 2121149 To determine the effects of an aldose reductase inhibitor (ARI) on diabetes-induced cardiac sympathetic disturbance, the effects of (E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene] rhodamine (ONO-2235), an aldose reductase inhibitor, as well as insulin on the responsiveness to the transmural sympathetic nerve stimulation (TNS) and norepinephrine (NE) of isolated right atria of streptozotocin-induced diabetic rats were investigated. 2.
721 2121569 Staurosporine, a protein kinase C inhibitor, blocked glyburide-, tolbutamide-, and insulin-stimulated glucose uptake.
722 2145873 In the present study the effects of 1 h intravenous infusion of alpha-human atrial natriuretic peptide (24 ng/min/kg) on systemic and renal hemodynamics and on renal excretory function were studied in six insulin-treated and metabolically well-controlled patients with diabetes mellitus (DM) type I and in six healthy control subjects (C).
723 2146178 In diabetic rats, the infusion of 1 nM GLP-I or GIP in perfusates with varying glucose concentrations (2.8, 5.6, 8.3, 11.1, or 22.2 mM) caused a nearly equal degree of insulin stimulation from a similar basal insulin level.
724 2146735 We measured ODC activity, of ventricular homogenates obtained from diabetic SHR and nonhypertensive WKY rats, with and without chronic treatment with insulin or triiodothyronine (T3).
725 2146735 Both T3 and insulin therapy prevented the decline in ventricular ODC activity in both strains, although only the effect of insulin was correlated with LVW.
726 2226108 Lowering fasting blood glucose to normal with a basal insulin supplement reduces endogenous insulin production, and this may be advantageous if accompanying production of islet amyloid polypeptide and islet amyloid formation are also reduced.
727 2227123 Moreover, although intravenous injection of CGRP (5.67 nmol/kg) elicited a significant increase in plasma epinephrine and norepinephrine concentrations, concomitant administration of epinephrine and norepinephrine, inducing a more prominent rise in plasma catecholamines than those induced by CGRP, affected neither plasma glucose nor insulin levels.
728 2227123 Finally, plasma insulin levels obtained by simulating CGRP-induced changes in plasma glucose or glucose plus catecholamine levels by infusion of glucose or glucose plus catecholamines were not different from those induced by CGRP injection.
729 2227123 These results suggest that CGRP has a hyperglycemic action that is not mediated by sympathetic outflow in conscious rats, and inhibition of insulin secretion, if any, does not play a major role in this hyperglycemic action of CGRP.
730 2227128 HLA-DR phenotype and glycosylated hemoglobin were determined at study entry, and insulin requirement, glucagon-stimulated C-peptide, ICAs, and IAs were measured at entry and after 1, 3, 6, 9, and 12 mo of follow-up.
731 2227134 The time course of pp185 phosphorylation at 37 degrees C was rapid and corresponded closely to insulin-receptor autophosphorylation but preceded insulin-stimulated glucose transport.
732 2227135 During hyperinsulinemic glucose-clamp studies, intravenous infusion of calcitonin gene-related peptide (CGRP) in rats antagonized the ability of insulin to stimulate peripheral glucose disposal by 52% (196 +/- 7.2 vs. 105 +/- 10.5 mumol.kg-1.min-1, P less than 0.05) and to inhibit hepatic glucose output by 54% (P less than 0.01).
733 2227135 CGRP also inhibited the in vitro effects of insulin to stimulate hexose uptake in cultured BC3H1 myocytes at all insulin concentrations studied.
734 2227135 Therefore, amylin and CGRP can cause insulin resistance in vivo and may be implicated in insulin-resistant states such as type II diabetes mellitus.
735 2237405 We conclude that in NIDDM underexpression of GLUT-2 messenger RNA lowers high Km glucose transport in beta cells, and thereby impairs glucose-stimulated insulin secretion and prevents correction of hyperglycemia.
736 2173562 Impairment in insulin-stimulated breakdown of the molecule in adipocytes of streptozotocin-diabetic rats was found, consistent with the impaired insulin activation of pyruvate dehydrogenase and glucose utilization seen in this model.
737 2175290 Two days after DEN, insulin binding to liver membranes and insulin removal by the liver were sharply reduced whereas its binding to muscle and adipocyte membranes remained unaltered.
738 2241998 Insulin administration reverses the change in the activity of glutathione peroxidase but does not reverse the glutathione reductase activity during diabetes.
739 2243134 Reduction in GLUT-2 correlates temporally with and may contribute to the loss of glucose-stimulated insulin secretion that precedes profound beta-cell depletion of autoimmune diabetes.
740 2245040 IGF-I and IGF-II promoted thymidine incorporation into cells at a half-maximal dose of 3 and 1 nM respectively, IGF-II with a maximum potency 65% of IGF-I; insulin stimulated at a half-maximum dose of 100 nM, with similar maximum effect to IGF-I, and their effects were not additive.
741 1979763 The circulating noradrenaline levels were higher during the infusion of pork insulin which also yielded a more prominent response of pancreatic polypeptide and, after cessation of the insulin infusion, plasma cortisol was also higher following pork insulin.
742 1980258 The effect of cyclic somatostatin on circulating insulin levels was studied in eight patients with insulin-dependent diabetes mellitus (IDDM).
743 1980258 Somatostatin increased the plasma insulin levels, corrected for the changes of hematocrit, by approximately 8% in the low dose (P less than 0.05) as well as in the high dose (P less than 0.05) period.
744 2148776 The effects of insulin treatment on plasma renin activity (PRA), plasma atrial natriuretic peptide (ANP) and body fluid volume were studied in 16 hospitalized patients with insulin-independent diabetes mellitus.
745 2148776 Thus, a vasodilatory action of insulin may assist in compensation for the increase in body fluid volume, preventing a rise in plasma ANP levels.
746 2149165 These studies demonstrate that the relative glycemic state does not influence GLUT-4 glucose transporter mRNA expression in vivo and strongly suggests that insulin is a major factor regulating the levels of GLUT-4 mRNA in adipose tissue.
747 2175805 Such an activation of phospholipase C would result in the formation of 1,4,5-inositol trisphosphate, a release of intracellular calcium and then release of insulin to the extracellular space.
748 2176470 Moreover, insulin administration for 5 days to diabetic animals did not affect their lowered intestinal polyphosphoinositide turnover, but did further accentuate their increased 1,2-diacylglycerol mass and synthesis de novo; this treatment also corrected total protein kinase C activity by increasing the cytosolic activity of this enzyme.
749 2176470 These results indicate that signalling mechanisms involving polyphosphoinositides, 1,2-diacylglycerol and protein kinase C are abnormal in the intestines of diabetic rats and that some of these biochemical parameters can be modulated by insulin administration in vivo.
750 2177838 After the administration of insulin, both S14 run-on activity and mRNAS14 levels were rapidly induced.
751 2177838 Within 1 h of insulin administration, S14 run-on activity and mRNAS14 were induced 5- and 8-fold, respectively.
752 2177838 Fructose administration to starved diabetic rats induced only a marginal 60% increase in mRNAS14 and S14 run-on activity within 4 h, while insulin plus fructose or insulin plus glucose fully restored S14 gene expression to intact levels within the same time period.
753 2177838 Acute effects of dietary carbohydrate on hepatic S14 gene transcription are insulin dependent.
754 1981060 A certain HLA-DQA2 locus TaqI fragment, DX alpha"U", has been reported to be associated with insulin-dependent diabetes mellitus (IDDM).
755 2076025 Serum levels of 3-hydroxybutyrate (3-OHBA), acetoacetate (AcAc) and 3-OHBA/AcAc ratio before breakfast were significantly increased in insulin-treated NIDDM patients with well-controlled fasting plasma glucose levels and IDDM patients compared to those in normal subjects.
756 1710739 The central, abdominal distribution of adipose tissue in IDDM is associated with insulin resistance, hypertension, and the above lipoprotein abnormalities.
757 1965428 Insulin release by human insulinoma cells was enhanced at 2 x 10(-7) M by glucagon, GLP-1[1-37], GLP-1[7-36] and its N- and C-terminal fragments GLP-1[7-14] and GLP-1[31-37].
758 1965428 These results suggest that GLP-1[7-36] stimulates insulin release by a direct action on human and rat B-cells, partly involving modulation of intracellular cyclic AMP.
759 2086453 It has been postulated that one of the factors causing immune-mediated pancreatic beta-cell destruction in insulin-dependent diabetes mellitus (IDDM) is interleukin-1 (IL-1).
760 2086453 Rat pancreatic islets exposed to human recombinant IL-1 beta (rIL-1 beta) for 48 h in vitro exhibit a markedly reduced glucose-stimulated insulin secretion.
761 2088457 The influence of metabolic control (HbA1c), noradrenaline (NA) and insulin-like growth factors (IGF-I and IGF-II) on renal function and size was investigated in 11 insulin-dependent diabetes mellitus patients aged 11-17 years.
762 2091054 Lactation in IDDM women may be influenced by hyper- or hypoglycemia as women balance their insulin needs.
763 2096182 Insulin-dependent diabetes mellitus (IDDM) is associated with several DR3- or DR4-containing ancestral haplotypes (AHs).
764 2097094 Therefore, we examined the influence of NPY alone and together with noradrenaline (NA) on insulin release in the rat.
765 2097094 When infused alone for 30 min under basal conditions, NPY increased basal plasma insulin concentrations by 32 +/- 13 microU/ml at the highest dose level tested (68 pmol/min), as compared to +7 +/- 7 microU/ml in the controls (p less than 0.05).
766 2097094 In contrast, NPY at 17 pmol/min reduced the plasma insulin response to both glucose (by 11%; p less than 0.001) and to arginine (by 26%; p less than 0.001).
767 2097094 In isolated rat islets, both NPY (10(-6) M) and NA (10(-6) M) inhibited glucose-stimulated insulin secretion.
768 2097094 We conclude that, in the rat, NPY and NA both elevate basal plasma insulin levels and inhibit stimulated insulin secretion.
769 2097094 In combination, NPY also induces a more rapid onset of the inhibitory action of NA on glucose-induced insulin secretion.
770 2099324 A reduction of heparin cofactor II (HCII) biological activity, despite its normal plasma concentration, is reported in insulin-dependent diabetic patients.
771 2103305 To test whether periodical exposure of the endocrine pancreas to circulating IL-1 beta in vivo affects insulin release from the intact perfused pancreas, rats were treated with daily intraperitoneal injections of 4 micrograms IL-1 beta/kg or saline for 5 days.
772 1846101 When H2b was added before ATP, insulin stimulated exogenous kinase activity of diabetic-derived receptors was significantly higher (approximately 50%) than control values at low H2b concentrations, but significantly lower (approximately 50%) than control values at high H2b concentrations, suggesting a decrease in the apparent Km and maximal velocity of the diabetic receptor tyrosine kinase toward H2b.
773 1846108 Changes in fetal insulin and glucose may be related to changes in expression of the IGF-I and IGFBP-1 genes in the growth-retarded fetuses.
774 1966731 Calcitonin gene-related peptide (CGRP) is an intrapancreatic neuropeptide that is known to inhibit glucose-stimulated insulin secretion in rats.
775 1966731 It was found that insulin secretion stimulated by glucose (8.3 mM) was inhibited by 77% by CGRP at 10(-6) M (p less than 0.001) and by 48% by the peptide at 10(-7) M (p less than 0.05).
776 1966886 Insulin-induced tyrosine kinase activity of partially purified insulin receptor measured using poly-glutyr as substrate was also lower in cells from diabetic rats (normal:1.4 +/- 0.6-fold; diabetic 0.5 +/- 0.3-fold above baseline; (p less than 0.05).
777 1984341 Thus, in NIDDM subjects, glucose and insulin responses to different mixed meals do not appear to be exclusively mediated by GIP.
778 1985898 Thus, glucose transport activity in the intact cell with PMA and insulin correlates more closely with the appearance of GLUT4 in the plasma membrane than cytochalasin B-assayable glucose transporters.
779 2129751 At an intermediate concentration, 0.5 ng/ml, rIL-6 preserved insulin secretion by islets cocultured with 2 ng/ml of human recombinant interleukin 1 beta (rIL-1 beta) which otherwise inhibited insulin secretion to 60% of islets cultured in medium alone.
780 2129751 We conclude that human IL-6 stimulates insulin production and secretion in vitro and induces similar ultrastructural changes in beta-cells as does IL-1 beta.
781 2132182 It is proposed, therefore, that insulin deficiency may lead to a perturbation in either the intrinsic kinetic behaviour of glucokinase or the participation of its regulatory protein, independently of any change in glycemia.
782 1671378 DA turnover was significantly reduced in striatum and hypothalamus in all diabetic groups. 5-HT turnover was reduced in chronically hyperglycemic diabetic rats in all four brain regions but normalized in insulin-treated diabetic rats.
783 1671798 In contrast, both insulin (100 pg/ml-10 ng/ml) and insulin-like growth factor-1 (1-100 ng/ml) had no effect on cAMP-stimulated aromatase but potentiated the action of dexamethasone (100 nM).
784 1705004 IGFBP-1 expression has been shown to increase under low-insulin conditions such as diabetes, and the complex regulation of expression is indicated by our finding that insulin treatment of H35 rat hepatoma cells, which induces proliferation, also causes a rapid decrease in transcription and expression of the IGFBP-1 gene.
785 1846745 The effects of the diabetic state on adenylate cyclase and surfactant secretion were reversed by in vivo but not in vitro insulin treatment.
786 1846830 However, when compared with nondiabetic control subjects, insulin-receptor kinase assays of wheat-germ-purified receptors prepared from her fibroblasts showed very low basal and no insulin-stimulated tyrosine kinase activity.
787 1846830 This insulin-receptor-deficient fraction inhibited both basal and insulin-stimulated tyrosine kinase activity of highly purified insulin receptors.
788 1899653 All but 2 of the 12 insulin-dependent diabetic eyes (IDDM), however, had reduced levels of retinal tPA immunoreactivity which was most pronounced in their peripheral retinas.
789 1991439 Therefore, we examined the effect of intravenous motilin on gastric emptying of a 99mTc colloid-labeled semisolid test meal in 9 insulin-dependent diabetic patients with diabetic gastroparesis.
790 1991576 It was found that the trypsin inhibitor N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) counteracted the acute stimulatory effects of IL-1 beta on islet glucose oxidation, insulin release, and biosynthesis.
791 1991576 TLCK also partially or completely counteracted the long-term inhibitory effects of IL-1 beta on islet glucose oxidation, insulin biosynthesis, content, and release.
792 1992187 To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, we studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration.
793 1993948 Because insulin-dependent diabetes mellitus is associated with altered electrolyte metabolism and a derangement of the parathyroid hormone (PTH)-vitamin D endocrine system, we studied 23 children with diabetes (age 9.4 +/- 2.5 years) and found lower serum values for total and ionized calcium, magnesium, intact PTH, calcitriol, and osteocalcin than in age- and sex-matched control subjects.
794 1999269 Like CGRP, IAPP antagonizes the action of insulin mainly at the level of muscle glycogen synthesis, but the levels required for this effect seem to be considerably higher than reported circulating levels.
795 1999433 We conclude that glucokinase expression in AtT20ins cells may be necessary, but is not sufficient to confer glucose-stimulated insulin secretion.
796 1999482 To identify the putative postreceptor lesion responsible for insulin resistance in Pima Indians, we investigated the influence of insulin on the activity of casein kinase II (CKII) in skeletal muscle of seven insulin-sensitive, four insulin-resistant, nondiabetic, and five insulin-resistant diabetic Pima Indians during a 2 h hyperinsulinemic, euglycemic clamp.
797 1999482 These results suggest that insulin stimulates CKII activity in human skeletal muscle by a mechanism involving phosphorylation of either CKII or of an effector molecule, and support the idea that elevated basal activity in resistant subjects results from insulin action.
798 1999482 It appears that the ability of insulin to activate CKII in skeletal muscle is not impaired in insulin-resistant Pima Indians, and that the biochemical lesion responsible for insulin resistance occurs either downstream from CKII or in a different pathway of insulin action.
799 1999488 A major portion of insulin-mediated glucose uptake occurs via the translocation of GLUT 4 glucose transporter proteins from an intracellular depot to the plasma membrane.
800 1999488 We have examined gene expression for the GLUT 4 transporter isoform in subcutaneous adipocytes, a classic insulin target cell, to better understand molecular mechanisms causing insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) and obesity.
801 1999488 In obesity, cellular depletion of GLUT 4 primarily involved low density microsomes (LDM), leaving fewer transporters available for insulin-mediated recruitment to the plasma membrane (PM).
802 1999488 We conclude that, in obesity, insulin resistance in adipocytes is due to depletion of GLUT 4 glucose transporters, and that the cellular content of GLUT 4 is determined by the level of encoding mRNA over a wide range of body weight.
803 1999488 Thus, pretranslational suppression of GLUT 4 transporter gene expression may be an important mechanism that produces and maintains cellular insulin resistance in NIDDM.
804 2006934 Insulin-dependent diabetes mellitus is associated with an increased frequency of certain histocompatibility antigens located on chromosome six, the most common types being B-8, B-15, DR-3, DR-4, and DR-7.
805 1672658 Somatostatin did not inhibit the early exaggerated insulin release, suggesting that these increased insulin levels represented leakage of insulin from damaged HIT cells rather than functional insulin secretion.
806 1672728 Both splits also distinguish each of the two DR3-bearing extended haplotypes (HLA-B8,SCO1,DR3,DQw2,Dw24 and B18,F1C30,DR3,DQw2,Dw25) found associated to several autoimmune diseases as insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE) and myasthenia gravis.
807 1826300 Normal animals showed compensatory increases in several measures of insulin secretion (fasting insulin [FI], acute insulin response to arginine [AIRarg], acute insulin response to glucose [AIRgluc], and glucose potentiation slope [delta AIRarg/delta G]), with no net change in fasting plasma glucose (FPG) or glycosylated hemoglobin (HbAtc).
808 1849848 These findings suggest that, despite resistance to physiological levels of insulin, the high circulating insulin concentrations present in the serum of these patients could mediate unwanted tissue-specific growth through an intact IGF-I receptor-effector mechanism.
809 1902426 To elucidate the effect of an aldose reductase inhibitor (ponalrestat) on kidney function in uncomplicated insulin-dependent diabetes mellitus (IDDM), 20 normoalbuminuric IDDM patients were randomized to follow either 6 mo of treatment with ponalrestat (n = 11, mean +/- SD age 30 +/- 8 yr, diabetes duration 10 +/- 6 yr) or 6 mo of placebo (age 33 +/- 7 yr, diabetes duration 12 +/- 6 yr).
810 2019256 Induction of diabetes with streptozocin decreased the GLUT4 to GLUT1 ratio in adipose tissue 4-fold and 24 h of insulin treatment of the diabetic rats increased this ratio 9- to 10-fold.
811 2022302 During 180-min euglycemic insulin-clamp (21.5 pmol.kg-1.min-1) studies, amylin (50, 200, or 500 pmol.kg-1.min-1; plasma concentration from 3 x 10(-10) to 9 x 10(-9) M) infusion determined a 19-27% reduction in glucose uptake (117.8 +/- 7.0 vs. 145.8 +/- 11.0, 107.1 +/- 9.2 vs. 145.1 +/- 6.7, and 105.0 +/- 7.2 vs. 144.4 +/- 7.0 mumol.kg-1.min-1 at 50, 200, or 500 pmol.kg-1.min-1, respectively, P less than 0.01) versus insulin alone, whereas 10-pmol.kg-1.min-1 amylin infusion (plasma concn 5 x 10(-11) M) failed to affect insulin-mediated glucose disposal.
812 2022302 Suppression of hepatic glucose production by insulin was unaffected by a 50-pmol.kg-1.min-1 amylin infusion (18.5 +/- 4.3 vs. 21.7 +/- 2.9 mumol.kg-1.min-1), whereas it was slightly but significantly impaired by amylin infusion at 200 pmol.kg-1.min-1 (17.8 +/- 3.9 vs. 24.7 +/- 4.5 mumol.kg-1.min-1, P less than 0.05).
813 2022306 The effect of activators of protein kinase C (PKC) on cytosolic concentration of free Ca2+ [( Ca2+]i) was assessed in insulin-secreting islet cell line HIT T-15.
814 2025268 GLUT4 mRNA levels were not significantly different between control and insulin resistant rats in all animal models.
815 2028355 Other circulating hormones, such as the newly characterised islet amyloid polypeptide (amylin), may also cause insulin resistance.
816 2028716 We examined the effects of T3 and insulin on the activity of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and cytosolic malic enzyme in control, thyroidectomized, thyroidectomized food-restricted, and thyroidectomized diabetic rats.
817 2028716 The data suggest that insulin may act on malic enzyme synthesis through its general stimulatory effect on protein synthesis, or by antagonizing factors that inhibit the induction of this enzyme.
818 1645253 Prior exposure of cells to 100 nmol/liter GLP-(7-37) (10 min) did not alter the GIP-induced (10 nmol/liter) insulin release, but 100 nmol/liter GIP (10 min) reduced the insulin secretion during stimulation with 10 nmol/liter GIP by 56%.
819 2035711 IL-1 beta has been reported to stimulate insulin secretion, suggesting that some of the effects of IL-1 beta are mediated by insulin.
820 2035711 The purpose of the current experiments was to study the possible role of endogenous insulin in physiological sleep regulation and in the hypnogenic effects of exogenously administered IL-1 beta.
821 2035711 These results indicate that, although sleep is disturbed in diabetic rats, pancreatic insulin might not have a decisive role in the regulation of sleep in rats, and it does not mediate the effects of IL-1 beta on sleep-wake activity.
822 2039509 These results which suggest that different isomeric forms of human GAD exist in brain and pancreas may be relevant to the pathogenesis of stiff man syndrome (SMS) and insulin-dependent diabetes mellitus (IDDM), respectively, two distinct but associated clinical disorders in which GAD is the target of autoantibodies.
823 2043220 It remains to be established whether this effect of captopril can be extrapolated to other ACE inhibitors, and the extent to which effects on insulin sensitivity will influence the long-term consequences for future risk of diabetes mellitus and coronary heart disease in patients with essential hypertension.
824 2043226 In insulin-dependent diabetes mellitus, an excess frequency of raised blood pressure occurs in association with increased urinary albumin excretion.
825 1648732 Insulin and insulin-like growth factor I (IGF-I) initiate their metabolic, growth, and differentiation effects through binding to the insulin receptor and the IGF-I receptor, two members of the tyrosine kinase family of receptors.
826 1829459 In addition, the inhibition of insulin-stimulated glucose transport activity in both red and white muscle precedes the decrease in GLUT4 protein and mRNA levels.
827 1829459 Thus, STZ treatment initially results in a rapid uncoupling of the insulin-mediated signaling of glucose transport activity which is independent of GLUT4 protein and mRNA levels.
828 2059220 With all three experimental models, exposure to human amylin acid and human and rat amylin at concentrations as high as 100 nM had no significant effect on rates of insulin or glucagon secretion.
829 2060427 The goal of this study was to assess whether children and adolescents with insulin-dependent diabetes mellitus (IDDM) have decreased catecholamine responses to insulin-induced hypoglycemia as has been reported in adults and to explore the pathogenesis of the decreased response in terms of possible relationships to autonomic neuropathy or hyperinsulinism.
830 2065011 Mice with the insulin II promoter expressed dbl protein in the pancreas but showed no evidence of diabetes and no apparent pancreatic beta-cell defects.
831 2065848 Fasting plasma islet amyloid polypeptide concentrations and their responses to an oral glucose load were determined in non-diabetic control subjects and patients with abnormal glucose tolerance in relation to the responses of insulin or C-peptide.
832 2065848 This study suggests that basal hypo-secretion of islet amyloid polypeptide relative to insulin exists in non-obese Type 2 diabetes and that circulating islet amyloid polypeptide may act physiologically with insulin to modulate the glucose metabolism.
833 2065857 Applied amylin levels of 220 +/- 75 pmol/l (infusion rate of 12.5 pmol/min) antagonized only the insulin action on liver, resulting in a 100% increase of hepatic glucose output.
834 2065857 Amylin did not affect: 1) the metabolic clearance rate of insulin, 2) the levels of plasma glucagon, epinephrine, norepinephrine, and corticosterone, 3) in vitro insulin binding and insulin-stimulated receptor autophosphorylation.
835 2065857 This suggests that amylin antagonizes insulin action via binding to a yet unknown receptor.
836 2065857 In conclusion: amylin causes in vivo insulin resistance and the liver seems the predominant organ regulated by this hormone.
837 2065857 The in vivo effects of amylin mimic the pathophysiological abnormalities of insulin action in Type 2 diabetes.
838 1650313 Continuous insulin inhibited PEPCK expression in a dose-dependent fashion with EC50 1 x 10(-11) M.
839 1650313 These observations suggest that insulin-mediated inhibition of PEPCK gene transcription is diminished by a pulsatile mode of administration in marked contrast to the pulse enhancement demonstrated for glucagon-mediated hepatic glucose production.
840 1650516 Oral feeding of coleonol for 7 days to normal rats causes increase in blood glucose, serum insulin, glucagon and free fatty acid levels with corresponding increase in glucose-6-phosphatase activity and depletion of liver glycogen.
841 1678384 Thus, in this glucose intolerance after hepatectomy, somatostatin seems to play an important role as a paracrine hormone by inhibiting the secretion of insulin by islet B-cells in the pancreas itself.
842 1713293 Treatment of diabetic rats with insulin resulted in a small, non significant increase in hepatic and renal IGF-I mRNA and a significant decrease in renal IGFBP-1 mRNA abundance.
843 1830258 The only haemorheological changes with insulin were increased levels of the platelet release proteins beta-thromboglobulin (37 (3) vs 28 (2) micrograms l-1, p less than 0.01) and platelet factor 4 (median 7.5 (range 3.0-18.0) vs 4.5 (2.0-10.5) micrograms l-1, p less than 0.01).
844 1858869 In conclusion, glucose oxidation is reduced at physiological insulin concentrations in NIDDM and cannot be explained by concomitant obesity, increased fat oxidation, or reduced glucose uptake but results from impaired sensitivity to stimulation by insulin, possibly at pyruvate dehydrogenase.
845 1859430 The decreased activity of acetylcholinesterase observed in diabetes may be due to an early impaired glucose oxidation and glucose transport as a result of lack of insulin, which causes specific alterations in neurotransmitter levels, thereby effecting blood brain barrier transport, thus causing brain dysfunction.
846 1860552 The isolated perfused normal rat pancreas was used to evaluate the effects of glucose and insulin secretagogues, such as arginine, beta-hydroxybutyrate, and gliclazide, on amylin secretion.
847 1864483 This study investigated the effect of insulin treatment on the development of overt diabetes, clinically inapparent anti-islet autoreactivity, and thyroiditis in RT6-depleted diabetes resistant BB rats.
848 1864483 We conclude that insulin treatment prevents clinical diabetes in the RT6-depleted diabetes resistant BB rat, but this treatment does not prevent the development of autoreactive cell populations that cause thyroiditis and adoptively transfer diabetes.
849 1864485 Flow cytometry analysis of spleen cell populations indicated that insulin increased the number of Thy1,2+ and Lyt-2+ T cells.
850 1868042 However, the ability of rIL-1 beta to suppress insulin secretion was not blocked by the 6-9-kDa inhibitor of IL-1 activity.
851 1868042 Unlike this IL-1 inhibitor, a monoclonal antibody specific for rIL-1 beta was able to neutralize both the islet cytotoxic and insulin modulatory effects of rIL-1 beta.
852 1651732 The activity of serum paraoxonase, an enzyme located on high-density lipoprotein, has been investigated in familial hypercholesterolaemia (FH) and insulin dependent diabetes mellitus (IDDM).
853 1832112 Brief exposure (1-2 h) of rat and mouse pancreatic islets to 10 ng/ml recombinant interleukin-1 beta induced an 70-80% inhibition of insulin response to glucose after 12 h.
854 1832357 Sensitivity of glucose disposal to exogenous insulin correlated positively with HDL-cholesterol (r = 0.65, p less than 0.05), HDL2-cholesterol (r = 0.59, p less than 0.05), and apolipoprotein A1 (r = 0.57, p less than 0.05) and negatively with apolipoprotein B (r = -0.53, p less than 0.05) and total: HDL-cholesterol ratio (r = -0.68, p less than 0.01).
855 1832357 Insulin insensitivity and hyperinsulinaemia were both associated with higher levels of hepatic lipase activity but did not influence lipoprotein lipase activity.
856 1887884 Acute injection of insulin led to a significant 1.6-fold increase in CK-M mRNA and a 2.2-fold increase of CK-B mRNA 5 h after insulin injection.
857 1888882 Suppression of both human and rat islet insulin secretion resulted from co-culture with recombinant interleukin-1 alpha (rIL-1 alpha) or interleukin-1 beta (rIL-1 beta); however, direct rIL-1 alpha and rIL-1 beta cytotoxicity was seen with rat islets but not with human islets.
858 1888882 Human islet insulin secretion was also suppressed during co-culture with recombinant tumor necrosis factor (rTNF) or interferon (rIFN), but not with lymphotoxin (rLT) or rIL-6; rat islet insulin secretion was not suppressed by any of these cytokines.
859 1909136 In insulin dependent diabetes mellitis (IDDM) beta cell destruction is associated with infiltration of the pancreatic islets by T lymphocytes and macrophages.
860 1909352 Insulin deficiency decreases tissue protein synthesis, albumin mRNA concentration, and albumin synthesis in rats.
861 1909861 The biological mechanisms underlying the direct (HLA, INS) and indirect (Gm-TCRB, Gm-HLA, Gm-INS) effects of these genetic regions on IDDM susceptibility remain to be elucidated.
862 1655527 It has been proposed that the cytokine interleukin-1 beta (IL-1 beta), secreted by islet-infiltrating macrophages, may be involved in the pathogenesis of insulin-dependent diabetes mellitus by participation in beta-cell destruction.
863 1655527 It was found that IL-1 beta markedly decreased beta-cell DNA synthesis, insulin secretion and cyclic AMP content.
864 1655527 The protease inhibitor N alpha-p-tosyl-L-lysine chloromethyl ketone, recently shown to protect completely against IL-1 beta-induced suppression of insulin production and secretion, was found to markedly reduce DNA synthesis without affecting insulin secretion.
865 1680775 Tests were performed of the effects of the Somatostatin (SMS) upon the concentration of Insulin, Glucagon and STH, as well as of the effects of SMS upon the specific binding of the insulin to the receptors.
866 1893147 Mononuclear cells from both healthy donors and diabetic patients could inhibit the insulin release with no correlation to TNF content.
867 1911706 Special attention was given to lipoprotein lipase (LPL) activity in tissues and to postheparin plasma LPL activity and hepatic lipase activity and their relation to insulin resistance.
868 1913321 After 2 weeks of insulin deficiency, fasting lipoprotein lipase activity was lowered in all tissues studied.
869 1913321 Insulin status had milder effects on lipoprotein lipase activity in vastus lateralis muscle than in the adipose tissues.
870 1913321 Thus the speed and extent of recovery of lipoprotein lipase activity following hormone replacement in insulin-deficient animals varied widely among tissues.
871 1913321 These findings suggest that insulin is part of the factors that determine the tissue specificity of lipoprotein lipase regulation.
872 1915075 Insulin-stimulated glucose uptake into muscle and fat involves regulation of the subcellular distribution and the expression of a specific facilitative glucose transporter protein (GLUT4).
873 1915075 Peripheral glucose uptake is lowered in diabetes, and the expression of GLUT4 is depressed in animals that have been made diabetic (i.e. insulin deficient) by destruction of the pancreatic beta-cells.
874 1915077 By immunofluorescence and Western blotting we studied whether glucose or insulin is the primary extracellular signal for inducing GLUT-1 expression in hepatocytes.
875 1915077 Chronic insulin treatment of diabetic rats reduces the number of rows of hepatocytes expressing GLUT-1 from approximately four to approximately two.
876 1915077 In contrast, chronic insulin infusion into nondiabetic rats does not affect the number of hepatocytes expressing GLUT-1.
877 1916058 During the study endogenous insulin secretion was suppressed by somatostatin (450 micrograms/h) and replaced by insulin infusion (0.15 mU.kg-1.min-1). 3H-glucose was infused for isotopic determination of glucose turnover.
878 1922015 Agents such as epidermal growth factor, insulin and platelet derived growth factor which stimulate their respective receptor-PTK activities were without effect on PTK activities of mammary carcinoma.
879 1718800 We measured the percentages of B lymphocytes that expressed the CD5 determinant in 93 control subjects (age range 1 day to 59 yr, mean +/- 22.6 +/- 17.7 yr), 17 subjects with newly diagnosed insulin-dependent diabetes mellitus (IDDM; range 5-29 yr, mean +/- SD 13 +/- 5.9 yr), 31 high-risk islet cell antibody (ICA)-positive nondiabetic subjects (range 4-45 yr, mean +/- SD 19.8 +/- 14.1 yr), and 13 subjects with IDDM of greater than 5 yr duration (range 10-43 yr, mean +/- SD 24.2 +/- 9.9 yr).
880 1719386 The insulin-like growth factor-binding proteins (IGFBPs) are thought to determine the distribution of IGF-I and IGF-II between the blood and tissue compartments and to modulate their biological activities.
881 1719386 A dynamic metabolic role for one of the IGFBPs, IGFBP-1, is suggested by the fact that plasma IGFBP-1 was increased after fasting and diabetes and rapidly decreased by refeeding or insulin treatment, respectively.
882 1719386 Insulin inhibited IGFBP-1 in the medium by 80% in the absence of glucose, suggesting that the inhibition is a direct effect of insulin; glucose exerted a smaller independent effect in the absence of insulin.
883 1719386 Insulin decreased IGFBP-1 mRNA in H4-II-E cells by 50% within 1 h and by 90% after 2-12 h of incubation.
884 1719386 Pretreatment of H4-II-E cells with dexamethasone stimulated IGFBP-1 transcription and increased steady state IGFBP-1 mRNA; stimulation was abolished by insulin treatment, indicating that inhibition by insulin was dominant over induction by dexamethasone.
885 1719559 We hypothesized that insulin and insulin-like growth factor type I (IGF-I) can influence synthesis of PAI-1, thereby potentially attenuating fibrinolysis.
886 1719559 Accumulation of PAI-1 protein in conditioned medium over 24 hr was stimulated more with insulin alone than with the combination.
887 1933958 In conclusion: at rest, myocardial lactate and aminoacids uptake is markedly impaired in IDDM without coronary artery disease; the metabolic abnormalities of the diabetic myocardium is not a primary phenomenon but rather a consequence of hypoinsulinemia and hyperglycemia because insulin administration, resulting in normoglycemia, restored normal patterns of cardiac metabolism.
888 1659172 These results suggest that in IDDM patients, HCHF diets enhance peripheral glucose disposal, decrease basal insulin requirements, and lower total cholesterol without altering glycemic control or triglycerides.
889 1660827 TGF-beta was a potent inhibitor of fetal hepatocyte proliferation in culture, whereas insulin potentiated fetal hepatocyte growth above "mitogen-independent" levels.
890 1683622 CCK-8, CCK-33, and GIP were all found to increase the basal plasma levels of insulin, somatostatin, and PP; the increases were observed already in samples taken at 2 min after the injection.
891 1683622 CCK-8, CCK-33, and GIP (100 pmol/kg) all potentiated the meal-induced plasma responses of insulin and PP, whereas plasma levels of glucagon after the meal were not affected.
892 1720333 CoQ6 and CoQ10 (ubiquinone), duroquinone and durohydroquinone did not stimulate insulin release.
893 1744120 The present study characterized the regulation of the genetic expression of the vasoactive peptide endothelin-1 (ET-1) by insulin in bovine aortic endothelial cells.
894 1744120 Moreover, the effects of phorbol 12-myristate 13-acetate (PMA) and insulin were additive in the induction of ET-1 gene expression.
895 1744120 When protein kinase C in the bovine aortic endothelial cells was down-regulated by preincubation with 8 x 10(-7) M PMA for 24 or 48 h, insulin was still able to increase ET-1 mRNA levels whereas PMA was ineffective.
896 1744120 Chem. 265, 10446-10450), we observed that 1.67 x 10(-8) M insulin increased CAT enzyme activity and mRNA levels.
897 1744120 The insulin dose-response curve observed for CAT activity correlated with that observed for ET-1 mRNA levels.
898 1745688 We conclude that hypnogenic and food-intake-reducing effects of exogenously administered CCK are closely associated; however, pancreatic insulin does not play a significant role in either of these effects.
899 1748056 These trials, which included assessment of insulin sensitivity by the euglycemic insulin clamp, showed that beta-adrenergic blockade and thiazide diuretic treatment (hydrochlorothiazide) increase insulin resistance and basal plasma insulin, whereas Ca(2+)-channel antagonists (verapamil and diltiazem), with the exception of the negative effect of nifedipine, are metabolically neutral. alpha-Adrenergic blockade with prazosin and angiotensin-converting enzyme (ACE) inhibition with captopril enhance insulin sensitivity.
900 1748062 Short-term studies have shown that octreotide, a long-acting somatostatin analog, blunts postprandial glycemic responses and reduces insulin requirement in insulin treated diabetic patients.
901 1950379 Additionally, amylin can induce peripheral insulin resistance, which might also be a cause for type II diabetes mellitus.
902 1953259 The main purpose of this randomized controlled study was to assess the effects of postmenopausal estrogen replacement therapy on blood pressure (BP) and plasma renin substrate (PRS) in non insulin-dependent diabetic patients (DNID).
903 1954811 Glycosylated hemoglobin improved with both methods of insulin delivery (P less than 0.01), but 8 of 10 CSII-treated patients achieved satisfactory glycemic control (HbA1 less than 50 mmol hydroxymethylfurfural/mol Hb), whereas only 3 of 10 CIT-treated patients achieved this (P less than 0.05).
904 1954811 Glycemic control improved with both methods of insulin treated patients achieved satisfactory glycemic control (HbA1 less than 50 mmol hydroxymethylfurfural/mol Hb), whereas only 3 of 10 CIT-treated patients achieved this CSII.
905 1958579 But it may turn out that IGF-I is the main regulator of SHBG and that, by interaction with the IGF-I receptors, insulin carries on its inhibitory activity on SHBG.
906 1959479 With respect to the key enzyme activities of glucose utilization, activation of glycogen synthase (increase of I-activity/total activity) and pyruvate kinase (activation at 0.2 mM phosphoenolpyruvate) was noted 4 h after insulin addition, and these effects were not abolished by cycloheximide.
907 1961115 To test the hypothesis that specific combinations of HLA and insulin gene polymorphism alleles may interact in providing susceptibility for IDDM, HLA-DR and 5' insulin gene insertion size have been determined in 300 individuals with IDDM.
908 1661694 When inhibition of receptor kinase activities was prevented by allowing maximal autophosphorylation of insulin receptors before addition of H2B, kinase activity of diabetic- and control-derived receptors was similar at all H2B concentrations.
909 1684554 To examine the relationship between the magnitude of the negative arterial-portal glucose gradient and net hepatic glucose uptake, two groups of 42-h fasted, conscious dogs were infused with somatostatin, to suppress endogenous insulin and glucagon secretion, and the hormones were replaced intraportally to create hyperinsulinemia (3- to 4-fold basal) and basal glucagon levels.
910 1755300 Serum albumin, transferrin, transthyretin (prealbumin), and retinol binding protein concentrations were determined in 74 children with insulin-dependent diabetes mellitus before and after a 10-day camp session during which blood glucose concentrations were controlled.
911 1756914 In individuals not using insulin, higher levels of IGF-I were associated with an increased frequency of PDR or moderate non-PDR (P = 0.08).
912 1763064 In the absence of adenosine receptor agonists, isoproterenol exerted a small (14%) but significant inhibition of the insulin-induced translocation of GLUT4 but had no effect on the translocation of GLUT1.
913 1763064 Thus, changes in the phosphorylation state and/or subcellular distribution of GLUT4 cannot account for the inhibition of insulin-stimulated glucose activity induced by isoproterenol.
914 1766505 Urine EGF was 119 +/- 7.9 ng/day at day 7 in the control rats but it was significantly increased from day 2 in the diabetic rats (320 +/- 52.9 ng/day at day 2 and 298 +/- 18.4 ng/day at day 7), while in the insulin-treated rats it was significantly less than that in the diabetic rats (134 +/- 8.34 ng/day at day 2 and 220 +/- 15.2 ng/day at day 7).
915 1772965 After each of the three interleukin-1 beta exposure periods, islet capacity to release insulin was decreased to 12, 6 and 3% of control, respectively, and islet insulin content decreased to 75, 56 and 21%, respectively.
916 1836995 These results suggested that rat liver-type phosphofructokinase mRNA in the liver was not under control of diet or insulin, in contrast to glucokinase and L-type pyruvate kinase.
917 1774018 Plasma levels of free insulin were almost identical during the two experiments indicating that insulin clearance is not influenced by hypoglycemia in patients with IDDM.
918 1778108 We have shown that elevated plasma D-glucose levels in experimentally-induced diabetic nude athymic rats can be reduced by intraperitoneal transplantation of microcarrier-attached insulin producing beta cells from the mouse pancreatic beta cell line, beta TC-1.
919 1778108 The reduction in the level of hyperglycemia was observed as early as two days following cell transplantation and was associated with a concomitant increase in plasma insulin levels. beta TC-1 cell transplanted diabetic rats had plasma D-glucose levels similar to those found in non-diabetic control animals and remained normoglycemic throughout the 39 day experimental period.
920 1787825 Amylin decreases insulin-stimulated glucose uptake in skeletal muscle and counteracts the ability of insulin to suppress output of glucose from the liver.
921 1788148 Amylin also decreased feeding induced by insulin administration without significantly affecting blood glucose levels.
922 1796306 In vitro experiment, isolated pancreas perfusion showed that alloxan-induced (14 mmol/L) perfusion fluid inhibition of insulin secretion could be reversed by pretreatment of bombesin (10(-3) mmol/L). (3).
923 1725033 Sixteen type 1, insulin-dependent diabetics with incipient nephropathy received ramipril, a long-acting ACE inhibitor, at hypotensive doses (treatment A: 5 mg/day, n = 8) or at nonhypotensive doses (treatment B: 1.25 mg/day, n = 8) during a 6-week, double-blind, parallel study to establish whether its antihypertensive effects could be dissociated from its local renal effects.
924 1725042 As well as glucose uptake, insulin has important effects on other aspects of cell function; for example, the hormone is an important regulator of the expression and function of the major inhibitory guanine nucleotide binding protein Gi.
925 1725042 Insulin is also involved in the regulation of cell growth, and in vascular smooth muscle cells there is evidence that this effect involves action of other growth factors, such as PDGF.
926 1797483 To assess the effect of puberty on the relationship between glycemic control and insulinlike growth factor I (IGF-I) levels in children with insulin-dependent (type I) diabetes mellitus.
927 1799920 Glycosylated hemoglobin (HbA1c) decreased from 9.57 +/- 2.01% while taking animal insulin to 8.97 +/- 2.00% on human insulin (rDNAE coli) (P less than 0.001) Serum cholesterol and triglyceride levels insulin (rDNAE coli).
928 1815119 The results indicate that insulin significantly (p less than 0.012) increases ALP by a mean value of 48% (from 5.4% to 215%) over matched controls.
929 1816977 Dephosphorylation of the insulin receptor by alkaline phosphatase resulted in an increase in insulin-stimulated autophosphorylation of the insulin receptor from STZ-D rats (43 +/- 13% to 66 +/- 14%, P less than 0.05), but not from normal rats (100% to 109 +/- 12%, NS).
930 1309347 Moreover, insulin, IGF-I, and/or calf serum are required for the autoregulatory negative transcriptional regulation of the TSH receptor by TSH/cAMP, as is the case for thyroglobulin.
931 1309768 Substitution of Tyr1146 in the insulin receptor regulatory region with phenylalanine partially impaired receptor autophosphorylation, pp185 phosphorylation, and insulin-stimulated increases in alpha PY-precipitable PtdIns 3-kinase activity.
932 1370155 Human galanin inhibited glucose-stimulated insulin secretion in a dose-dependent manner in RIN cells.
933 1726900 We investigated thyrotropin releasing hormone (TRH) degradation in terms of half-life (t1/2) and metabolic clearance rate (MCR) in eight subjects with insulin dependent diabetes mellitus (IDDM) before and after strict metabolic control.
934 1726900 These findings demonstrate that a) the degradation of exogenous TRH is not dependent on the glucose metabolic state, b) insulin deficient diabetes mellitus does not affect the enzymatic system responsible for TRH degradation and, c) the hypothalamic-pituitary axis appears to be intact in IDDM.
935 1726909 Staurosporine, an inhibitor of protein kinase C, also blocked the effects of insulin on RNA synthesis.
936 1727733 In poorly controlled insulin-dependent diabetes mellitus (IDDM), hyperglycemia fails to inhibit the pituitary response to growth hormone-releasing factor (GRF).
937 1727740 Furthermore, liver binding data were not due to cross-reaction of 125I-labeled insulin to the insulinlike growth factor I receptor, and treatment of liver membranes with neuraminidase did not alter the inhibitory effect of the IgGa fraction from patient I-2 on 125I-labeled insulin binding to liver.
938 1727740 Binding inhibition experiments performed with cells transfected with and overexpressing the -12 (human insulin receptor [HIR]-A) or the +12 (HIR-B) variant of HIR revealed that the IgGa fraction from patient I-2 inhibited 125I-labeled insulin binding to the HIR-A receptor but not to the HIR-B receptor.
939 1823641 To evaluate the relationship of blood ketone bodies with diabetic control and endogenous insulin secretion, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), fasting serum C-peptide (CPR), blood total ketone-bodies (TKB), blood acetoacetate (AcAc) and blood 3-hydroxybutyrate (3-OHB) were compared in 78 outpatients with non-insulin-dependent diabetes mellitus (NIDDM) treated with diet (n = 13), sulfonylurea (n = 52) and insulin (n = 13).
940 18411183 Islet amyloid polypeptide (IAPP or amylin), first identified as the peptide deposited as amyloid in type-2 diabetic pancreas and insulinoma, turns out to be a peptide produced in the pancreatic beta-cell secretory granule that is costored and coreleased with insulin.
941 1311671 Amylin significantly reduced insulin secretion in rat insulinoma cell lines (Rin m5F cells) that were stimulated by either isoproterenol and forskolin, but it did not affect insulin secretion stimulated by isobutyl-methylxanthine (IBMX) or dibutyryl cyclic-adenosine monophosphate (db-cAMP).
942 1346593 The responses of plasma epinephrine, norepinephrine, growth hormone, pancreatic polypeptide, and somatostatin were similar in both tests and, consequently, were not significantly modified by the circulating insulin level.
943 1536661 Compared with control rats, in insulin-deficient rats less of the phospholipid label was distributed to the lighter HDL fraction and more to the heavier HDL fraction, and this difference was not due to changes in activity of lecithin: cholesterol acyltransferase or in the apparent activity of phospholipid transfer protein.
944 1536868 Desaturase activities, which are partially inhibited by spontaneous diabetes during the normo- and hyper-glycemic periods, were similarly affected by the various insulin treatment; delta 9 desaturase activity being more depressed than the desaturase activities of either delta 6 of delta 5.
945 1538716 Analysis of mRNA abundance for Glut-4, lipoprotein lipase, and glucose-6-phosphate dehydrogenase showed that pioglitazone enhanced the insulin induction of these mRNA species.
946 1541051 We have recently reported that chronic and systemic administration of tumor necrosis factor alpha (TNF) inhibits development of autoimmune diabetes in NOD mice and BB rats, animal models of insulin-dependent diabetes mellitus (IDDM).
947 1541236 It has been reported that islet amyloid polypeptide (IAPP) has insulin antagonistic effects in vivo and in vitro.
948 1541236 Rat calcitonin gene-related peptide (CGRP), which has sequence homology with IAPP and has been reported to inhibit insulin action, was also administered.
949 1541236 Therefore, IAPP directly reduced only the insulin-mediated GU in the skeletal muscle, and this effect of IAPP occurred at the same dose as that of CGRP.
950 1541237 Intravenous injection of rat CGRP caused a significant increase in plasma glucose concentration with a simultaneous increase in plasma insulin levels, whereas neither IAPP-NH2 nor IAPP-COOH had any effect.
951 1541237 Moreover, intravenous infusion of CGRP decreased tolerance to intragastric administration of glucose (O-GTT) without altering plasma insulin levels, but again IAPPs had no effect.
952 1542265 In obese subjects, adipose tissue HSL and LPL fail to respond to immunoreactive insulin postprandially, which may be an important maladaptation in terms of lipoprotein metabolism and risk of coronary heart disease.
953 1542267 While several studies have shown that reduced sex hormone-binding globulin (SHBG) is associated with increased insulin and triglyceride and decreased high-density lipoprotein cholesterol (HDLC) in premenopausal women, little data are available for postmenopausal women.
954 1542267 SHBG was negatively associated with triglyceride (r = -.21) and insulin (r = -.47) concentrations and positively associated with HDLC concentrations (r = .47).
955 1542267 After adjustment for overall adiposity (body mass index) and upper body adiposity (as measured by the ratio of waist to hip circumferences), SHBG was still associated with HDLC and insulin, but not with triglyceride.
956 1312492 Treatment of the cells with phospholipase C at concentrations up to 3.4 U/ml did not affect specific insulin binding, but reduced insulin-stimulated receptor phosphorylation by 50%.
957 1312492 Insulin-stimulated phosphorylation of pp 185, the presumed endogenous substrate for the insulin receptor kinase, was also reduced following phospholipase C treatment, with an almost complete loss of insulin stimulation after exposure of cells to enzyme at concentrations as low as 0.6 U/ml.
958 1312492 In contrast to these effects of phospholipase C on intact cells, receptor autophosphorylation was not affected in insulin receptors purified on wheat germ agglutinin-agarose from phospholipase C treated cells.
959 1348845 Glucagon-like peptide-1 (7-36) amide (glucagon-like insulinotropic peptide, or GLIP) is a gastrointestinal peptide that potentiates the release of insulin in physiologic concentrations.
960 1348845 In the patients with IDDM, normoglycemic-clamp studies were performed during the infusions of GLIP and saline to determine the effect of GLIP on insulin sensitivity.
961 1533230 Treatment of diabetic rats with insulin for 7 d led to normalization of hepatic albumin mRNA levels with no substantial change in apo E mRNA levels.
962 1547673 A long-acting zinc human insulin injected before the evening meal can help to control persistent fasting hyperglycemia in IDDM patients.
963 1547687 In subjects taking insulin, glycosylated hemoglobin was correlated most strongly with total cholesterol.
964 1547918 To study whether insulin resistance in Type 2 (non-insulin-dependent) diabetes mellitus is due to a defect in the expression of the insulin-responsive glucose transporter gene (GLUT-4) in human skeletal muscle, we measured the level of GLUT-4 mRNA and (in some of the subjects) its protein in muscle biopsies taken from 14 insulin-resistant patients with Type 2 diabetes, 10 first-degree relatives of the diabetic patients and 12 insulin-sensitive control subjects.
965 1551314 Our results demonstrate that two models of insulin-deficient diabetes in the rat are associated with increased hypothalamic neuropeptide Y mRNA.
966 1554359 These results indicate that (a) the effects of diabetes and fasting are almost identical and lead to changes in GLUT-4 expression that are tissue-specific, (b) white adipose tissue, brown adipose tissue and heart respond similarly to insulin deficiency by decreasing GLUT-4 mRNA to a larger extent than GLUT-4 protein, and (c) red and white skeletal muscle respond to insulinopenic conditions in a heterogeneous manner which is characterized by enhanced GLUT-4 mRNA/protein ratios.
967 1559408 In these studies, pretranslational suppression of GLUT4 appears to be the key mechanism of insulin resistance in adipocytes.
968 1559408 However, levels of GLUT4 protein and mRNA are normal in vastus lateralis and rectus abdominis, inferring that defects in GLUT4 functional activity or insulin-mediated translocation cause insulin resistance in muscle.
969 1563116 Plasma amylin correlated closely with serum C-peptide (r = .764; p = 0.0001), and to a lesser extent with insulin (r = .595; p = 0.0001) underlining its postulated cosecretion with these peptides.
970 1563581 Reduced secretion of insulin and progressive islet damage (indicated by a significant reduction in residual islet insulin and DNA content) were demonstrated when microencapsulated islets were incubated with interleukin-1 beta in vitro for 9 days.
971 1563587 To study whether abnormal secretion of islet amyloid polypeptide is involved in the development of insulin resistance and impaired insulin secretion in Type 2 (non-insulin-dependent) diabetes mellitus, we measured islet amyloid polypeptide concentrations in 56 first-degree relatives of Type 2 diabetic subjects and in 10 healthy control subjects.
972 1563587 It is however, unlikely that islet amyloid polypeptide is involved in the development of insulin resistance as insulin-resistant relatives with normal glucose-tolerance showed normal islet amyloid polypeptide concentrations.
973 1568528 Our results indicate that glucose is involved in regulating GLUT2 mRNA and glucose uptake activity and that the glucose responsiveness of the insulin secretion correlates with the glucose-induced change in glucose uptake activity in HIT cells.
974 1568530 Poorly controlled insulin-dependent diabetes mellitus (IDDM) is associated with elevated basal plasma growth hormone (GH), disproportionally low insulin-like growth factor I (IGF-I) levels, and impaired somatic growth.
975 1569156 Fasting free plasma insulin levels were similar in control and IDDM subjects but hemoglobin A1c (HbA1c), fasting plasma glucose and free fatty acid levels were significantly higher in IDDM subjects.
976 1569156 No direct regulatory role of chronic glycemic control or plasma insulin levels on GLUT4 expression is evident.
977 1374869 Tight glycaemic control with insulin prevented completely the deficit in both peptides (substance P = 0.096 +/- 0.021, calcitonin gene-related peptide = 4.66 +/- 0.92).
978 1533588 The effect of the new ACE-inhibitor, fosinopril, on insulin sensitivity (SI), glucose homoeostasis and lipid profile has been examined in 24 young, healthy, normotensive men.
979 1533588 SI, fasting plasma glucose and insulin, serum total triglycerides (Tg) and lipoprotein cholesterol (C) fractions, and ACE activity were assessed after subjects had taken placebo for 1 week and after 3 further weeks either on placebo (12 subjects) or fosinopril 20 mg daily (12 subjects), administered in a double-blind, randomized order.
980 1534057 These findings suggest that amylin secretion may be preserved in diabetic rats with reduced beta-cell mass and that hyperglycemia may increase amylin production independently of that of insulin, which may be significant in the pathogenesis of non-insulin-dependent diabetes mellitus.
981 1570017 Glucokinase is an enzyme that catalyses the formation of glucose-6-phosphate from glucose and may be involved in the regulation of insulin secretion and integration of hepatic intermediary metabolism.
982 1573849 IAPP, a highly conserved and carboxy-terminally amidated 37 amino acid polypeptide with approximately 45% amino acid sequence identity to CGRP, is produced by islet beta cells and is cosecreted with insulin in response to glucose and other secretagogues.
983 1579999 Dietary regulation in IDDM is thus a compensation for the defective synchronization of variations in the plasma levels of glucose and insulin in the present day forms of insulin therapy.
984 1580274 We studied the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril, administered for 36 months on glycemic control, creatinine clearance, and albuminuria in hypertensive insulin-treated diabetics.
985 1581467 Previous studies have determined that daily low dose injections of the potent cytokine interleukin-1 beta (IL-1 beta) decreased the frequency of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone (DP) BB rats.
986 1587399 We conclude that glucocorticoids do not decrease GLUT4 content in skeletal muscle and that glucocorticoid-induced insulin resistance in this tissue is not due to suppression of glucose transporter gene expression.
987 1351429 The beta-cell/liver glucose transporter gene GLUT2 represents a good candidate for the etiology of the disease, being involved in the glucose signalling for beta-cell insulin release.
988 1351854 To investigate a potential association of an HSP70-2 gene polymorphism with insulin-dependent diabetes mellitus (IDDM), we analyzed restriction-fragment-length polymorphism (RFLP) of this gene in 29 families with one or more member affected by IDDM.
989 1376704 Aminoguanidine and NMMA are equipotent inhibitors of interleukin-1 beta-induced 1) nitrite formation (an oxidation product of NO.) and cGMP accumulation by the rat beta-cell insulinoma cell line RINm5F, and 2) inhibition of glucose-stimulated insulin secretion and formation of iron-nitrosyl complexes by islets of Langerhans.
990 1377136 In contrast, adding insulin resulted in progressive suppression of both IGFBP-1 protein and IGFBP-1 mRNA, 43% at 10(-10) M, 74% at 10(-9) M, and 83% (maximal) at 10(-8) M; ED50 of approximately 10(-10) M is within the physiological range of insulin concentrations.
991 1535055 We conclude that in human disease states characterized by insulin resistance, i.e., obesity, IGT, NIDDM, and GDM, GLUT4 gene expression is normal in vastus lateralis or rectus abdominis.
992 1535382 Insulin was able to prevent all of the observed changes while aminoguanidine protected against changes in accumulation of advanced glycosylation end products and resistance to enzymatic digestion but not against changes in collagen concentration.
993 1592161 Studies have shown that in circulating lymphocytes pyruvate dehydrogenase (PDH) is responsive to insulin. 2.
994 1600838 Several of these agents are discussed in this article under categories relating to their mechanisms of lowering blood glucose: 1) inhibition of the release or action of counterregulatory hormones; 2) inhibition of postprandial glucose rise; 3) sensitization of tissues to insulin's actions; and 4) inhibition of gluconeogenesis, including inhibition of the long-chain acyl-CoA-carnitine acyltransferase I, the long-chain acylcarnitine translocase, and pyruvate carboxylase.
995 1611134 We recently reported that the activity of aldose reductase was increased in erythrocytes of insulin-dependent diabetes mellitus patients but short-term hyperglycemia did not affect the enzyme activity.
996 1611832 No significant differences were found in body weight, HbA1C, insulin binding to erythrocytes, insulin and drug requirements, and other circulating lipids (cholesterol, HDL-cholesterol, phospholipids, Apolipoprotein A1, Apolipoprotein B).
997 1612068 With more physiologic insulin replacement and more accurate glucose monitoring, it was believed that very strict glycemic control of IDDM could be achieved without increasing the risks of hypoglycemia.
998 1612192 Insulin-dependent diabetes mellitus (IDDM) is associated with antibodies to a 64,000-M(r) islet cell protein, at least part of which is identified as glutamic acid decarboxylase (GAD).
999 1612192 We determined the frequencies of antibodies to intact GAD, tryptic fragments of islet 64,000-M(r) antigen, islet cell antibodies (ICAs), and insulin autoantibodies (IAAs) in sera from 58 nondiabetic identical twins of patients with IDDM, of whom 12 subsequently developed diabetes.
1000 1612205 Because increased concentrations of plasminogen activator inhibitor type-1 (PAI-1) occur also, we hypothesized that proinsulin and split proinsulin may augment endothelial cell PAI-1 expression, thereby potentially attenuating endogenous fibrinolysis and accelerating atherosclerosis.
1001 1612205 Proinsulin increased PAI-1 activity in conditioned media of endothelial cells as did split proinsulin, paralleled by increased expression of PAI-1 mRNA.
1002 1612205 These effects of proinsulin were not dependent on its conversion to insulin nor on its interactions with the insulin receptor.
1003 1612205 The proinsulin stimulation of PAI-1 expression was not attenuated by either anti-insulin receptor antibodies or a 100-fold excess of insulin.
1004 1612205 These results indicate that proinsulin augments PAI-1 expression, potentially contributing to vasculopathy in patients with non-insulin-dependent diabetes mellitus.
1005 1320027 The level of biological function approximately paralleled the insulin-stimulated tyrosine kinase activity in the intact cell as estimated by tyrosine phosphorylation of the insulin receptor and its endogenous substrate pp 185/IRS-1.
1006 1352286 To examine the role of the transmembrane domain (TM) of the insulin receptor in insulin-induced receptor kinase activation, we prepared four mutated insulin receptors: 1) a Val938----Asp substitution (IR/TMv----D), 2) insertion of a 3-amino acid repeat (Val938-Phe939-Leu940) (IR/TM+3), or the entire TM was replaced by the corresponding domain of either the 3) platelet-derived growth factor (PDGF) receptor (IR/TMPDGFR) or 4) c-neu/erbB2 proto-oncogene product (IR/TMc-neu).
1007 1385629 When diabetic rats were treated with insulin, the renal protection observed with the diabetic state was reversed (creatinine, 0.70 +/- .05 mg/dl); plasma ANP concentrations were also reduced (52.2 +/- 15.2 fmol/ml).
1008 1618927 Insulin regulates GAPDH gene transcription in a tissue-specific manner.
1009 1619503 Insulin-induced hypokalaemia increases plasma renin and angiotensin II levels while decreasing the serum aldosterone concentration.
1010 1625676 The intrinsic tyrosyl kinase activity of the insulin receptor is regulated by a balance between insulin-induced receptor autophosphorylation, which stimulates the receptor kinase, and enzymatic dephosphorylation of the receptor, which deactivates its kinase activity.
1011 1625684 The increase of urinary albumin excretion has a predictive value for cardiovascular disease in insulin-dependent and non insulin-dependent diabetics.
1012 1625685 In ongoing studies aimed at elucidating the mechanism of insulin action on the expression of genes that modulate glucose utilization and cell growth, we have focused on the inductive effect of insulin on transcription of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the early growth response gene, Egr-1.
1013 1625685 GAPDH mRNA is decreased in the epididymal fat cells of diabetic animals and is increased over control levels when insulin is replaced, while Egr-1 mRNA levels are increased in diabetic animals.
1014 1625685 We present evidence that supports the role of protein phosphorylation in mediating the effect of insulin on activation of Egr-1 and GAPDH gene transcription.
1015 1631088 We investigated in six low- and six high-insulin responders (LIR and HIR) the effect of dexamethasone (Dex, 15 mg orally during 48 hr) on oral glucose tolerance (OGTT), glucose turnover under basal conditions and during glucose infusion of 2 mg.kg-1.min-1, and insulin response during hyperglycemic clamp.
1016 1633634 The association of insulin-dependent diabetes mellitus and HLA began with weak associations of Class I antigens (B8 and B15) and progressed to Class II antigens (DR3 and DR4), then to subtypes of DR4 (Dw4, 10, and 14), and now to DQ molecules including the absence of aspartic acid at position 57 of the DQ beta chain and the presence of arginine at position 52 of the DQ alpha chain.
1017 1634622 These observations together with previously published data suggest that a factor different from glucose or insulin regulates the beta cell expression of GLUT2.
1018 1354782 These results suggest that mutant GCK may lead to chronic hyperglycaemia by raising the threshold of circulating glucose level which induces insulin secretion.
1019 1380182 By contrast, insulin stimulation of the p85 Rsk S6 kinase and mitogen-activated protein (MAP) kinase activity were unaffected by drug.
1020 1380456 IRS-1 undergoes rapid tyrosine phosphorylation during insulin stimulation and forms a stable complex containing the 85 kDa subunit (p85) of the phosphatidylinositol (PtdIns) 3'-kinase, but p85 is not tyrosyl phosphorylated.
1021 1380456 Furthermore, overexpression of IRS-1 potentiates the activation of PtdIns 3-kinase in insulin-stimulated cells, and tyrosyl phosphorylated IRS-1 or peptides containing phosphorylated YXXM motifs activate PtdIns 3'-kinase in vitro.
1022 1380456 We conclude that the binding of tyrosyl phosphorylated IRS-1 to the SH2 domains of p85 is the critical step that activates PtdIns 3'-kinase during insulin stimulation.
1023 1386818 Insulin (0.1-1.0 mu/ml) and IGF-I (10(-9) to 4 x 10(-9) M) stimulated renin secretion in normal tissue (control, 95 +/- 3%; insulin [0.5 mu/ml], 134 +/- 7%; IGF-I [4 x 10(-9) M], 149 +/- 7%).
1024 1386818 This study suggests that the low renin state in DM may be explained by the enhanced inhibitory effect of ANG II and the resistance to the secretogogue actions of insulin and IGF-I.
1025 1495454 The metabolic effects of a long-acting somatostatin analogue, octreotide, in type I diabetic patients on conventional insulin therapy have been evaluated.
1026 1499859 Na oleate had no effect on basal or insulin-stimulated concentrations of GLUT1 or GLUT4 proteins in the PM or LDM fractions.
1027 1499870 This strategy can avoid injections of somatostatin, which can have other affects in addition to the suppression of insulin and glucagon.
1028 1500426 These data suggest that the insulin receptor contains two tyrosine/beta-turns which contribute independently and additively to insulin-stimulated endocytosis.
1029 1637089 Islet amyloid polypeptide, or amylin, is co-localized with insulin to the beta-cell secretory granule and is synthesized and released in parallel with insulin in response to a range of physiological and pharmacological stimuli.
1030 1637089 IAPP was subsequently shown, like CGRP, to inhibit the release of insulin pharmacologically.
1031 1639013 In the present study, we used Northern blot analysis to evaluate the effects of insulin on the content of SP-A messenger RNA (mRNA) as well as on the content of mRNA for the hydrophobic surfactant-associated proteins SP-B and SP-C in human fetal lung explants maintained in vitro.
1032 1639013 Our findings provide evidence that insulin may delay fetal lung development by inhibiting SP-A and SP-B gene expression.
1033 1639206 In insulin-dependent diabetes, hypertension is generally preceded by microalbuminuria, known to be reduced by angiotensin converting enzyme inhibitors.
1034 1641390 Islet amyloid polypeptide (IAPP) has been recently identified as the principal constituent of amyloid deposits in pancreatic islets of patients with type 2 (non-insulin-dependent) diabetes mellitus and causes insulin resistance in some target cells.
1035 1643805 To assess the prevalence of hypercholesterolaemia and its relationship with metabolic control and urinary albumin excretion in Type 1 diabetic patients, all 1577 insulin-dependent patients attending the outpatient clinic at the Steno Memorial Hospital were studied.
1036 1355581 To study the effect of CRH on anomalous GH response to TRH, we tested with TRH (200 micrograms intravenously [IV]) and CRH (100 micrograms IV) + TRH (200 micrograms IV) 13 patients (six males and seven women) affected by insulin-dependent diabetes mellitus.
1037 1356098 The major histocompatibility complex (MHC) contains multiple and diverse genes which may be relevant to the induction and regulation of autoimmune responses in insulin dependent diabetes mellitus (IDDM).
1038 1381373 The class I response to TSH, serum, insulin, IGF-I, or hydrocortisone is specific, in that the same agents do not similarly affect TSH receptor, thyroglobulin, thyroid peroxidase, malic enzyme, or beta-actin RNA levels.
1039 1382160 Angiotensin-converting enzyme (ACE) inhibitors are superior to conventional antihypertensive drugs in preventing the development of glomerular lesions in insulin-treated streptozotocin diabetic rats.
1040 1387432 The present study examines the role of hyperinsulinemia, impaired atrial natriuretic release, and resistance to atrial natriuretic peptide action in determining sodium retention in normotensive and hypertensive insulin-dependent diabetic patients.
1041 1511780 However, in muscle from diabetic animals the ODC activity declined steadily during the 14 days to 34% of control values (P less than 0.01), and insulin treatment completely normalized the ODC activity in muscle.
1042 1512261 In attempts to correlate GLUT-1 and GLUT-2 expression to beta-cell function glucose uptake and glucose-stimulated insulin release in fresh and cultured islets were measured.
1043 1513099 In this study glomerular glucosaminyl N-deacetylase activity and urinary albumin excretion were measured in insulin-treated streptozotocin-diabetic rats.
1044 1516482 To assess whether proinsulin levels are elevated in first-degree relatives of insulin-dependent diabetes mellitus (IDDM) patients and whether there is a relationship between proinsulin levels and the occurrence of immunological markers.
1045 1516889 The effect of treatment with the somatostatin analogue octreotide ("Sandostatin") on GH secretion, IGF1 levels and metabolic control was investigated in insulin-dependent diabetics.
1046 1517369 We determined the effect of a 4-h insulin infusion on the expression of the muscle/adipose tissue (GLUT-4) glucose transporter mRNA and protein in 14 insulin-treated type 1 diabetic patients and 15 matched nondiabetic subjects.
1047 1517369 In response to insulin, muscle GLUT-4 mRNA increased in the nondiabetic subjects from 24 +/- 3 to 36 +/- 4 pg/microgram RNA (P less than 0.001) but remained unchanged in the insulin-resistant diabetic patients (24 +/- 2 vs. 26 +/- 2 pg/microgram RNA, before vs. after insulin).
1048 1520483 Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease and susceptibility to both IDDM and IgA deficiency is associated with HLA DQB1 alleles encoding non-Asp amino acids at position 57.
1049 1526316 Insulin inhibited the epinephrine-induced PG formation (P less than 0.01) but had no effects on the action induced by phospholipase A2.
1050 1327926 We evaluated whether insulin-receptor tyrosine kinase activity is required for activation of PDH, insulin-induced hydrolysis of PIG and generation of IG and 1,2-DAG.
1051 1328294 Insulin treatment of diabetic animals for 5 d restored glucose transport activity, GLUT-4 protein, and GLUT-4 phosphorylation to control levels whereas vanadate and phlorizin were ineffective.
1052 1328294 In control adipocytes, insulin promoted GLUT-4 translocation from the low density microsomal (LDM) pool to the plasma membranes (PM) and decreased the state of GLUT-4 phosphorylation.
1053 1382616 In addition, diabetes-induced changes in the extent of phosphorylation of phenylalanine hydroxylase are reversed by either insulin or vanadate treatment in vivo.
1054 1383692 The insulin-like growth factor-binding proteins (IGFBPs) are a family of proteins that specifically bind IGF-I and IGF-II, determine their bioavailability to tissues, and modulate their actions in target tissues.
1055 1395466 During the insulin suppression test, steady-state plasma glucose levels were 14.4 +/- 1.3 vs 14.2 +/- 1.1 mmol l-1 before and after chronic ACE inhibition, respectively, at comparable hyperinsulinaemic plateaux (291 +/- 21 vs 287 +/- 14 pmol l-1).
1056 1396993 Treatment of diabetic rats with an aldose reductase inhibitor, ONO-2235, which did not improve hyperglycemia, prevented the antiaggregating activity of plasma as did insulin treatment.
1057 1397706 The purpose of this study was to determine whether the restoration of glucose-induced insulin secretion was paralleled by an increase of GLUT2.
1058 1397712 Incubation of adipocytes from either group with 7 nM insulin did not recruit GLUT5 to the plasma membrane, in spite of a 54% insulin-stimulated increase in GLUT4 in nonobese subjects.
1059 1401944 We conclude: (1) subjects with thyroid disease and first degree relatives of IDDM patients frequently have high non-specific binding for IAA in an RIA not employing a cold displacement step, (2) in some newly diagnosed IDDM patients and first degree relatives of IDDM patients, IAA may be missed by an assay not optimized to measure specific binding, and (3) displacement with cold insulin increases both the specificity and sensitivity of RIAs measuring insulin autoantibodies.
1060 1407245 Furthermore, it has been shown that amylin has the potential to antagonize the action of insulin on glucose metabolism by increasing hepatic glucose production and by decreasing muscle, but not adipocyte glucose uptake.
1061 1411263 To determine whether altered levels of apolipoprotein(a) (apo(a)), the glycoprotein of the potentially atherogenic lipoprotein(a) (Lp(a)), contribute to the increased risk of ischaemic heart disease, apo(a) was determined in 50 insulin-dependent diabetic patients with diabetic nephropathy (group 1), in 50 insulin-dependent diabetic patients with microalbuminuria (group 2), in 50 insulin-dependent diabetic patients with normoalbuminuria (group 3), and in 50 healthy subjects (group 4).
1062 1330463 We report here the alterations of serum angiotensin-converting enzyme activity (S-ACE) and of active renin plasma concentrations (ARPC) in 41 insulin-dependent diabetes mellitus (IDDM) patients compared with those of 26 control subjects.
1063 1331176 These data indicate that: (a) IRS-1 protein levels are differentially regulated in liver and muscle; (b) insulin levels may play a role in this differential regulation of IRS-1; (c) IRS-1 phosphorylation depends more on insulin receptor kinase activity than IRS-1 protein levels; and (d) reduced IRS-1 phosphorylation in liver and muscle may play a role in insulin-resistant states, especially of the ob/ob mice.
1064 1385403 Insulin immediately stimulated tyrosine phosphorylation of IRS-1, and after 10-30 min with insulin its apparent molecular mass increased to 175-180 kDa.
1065 1385403 Purified insulin receptors directly phosphorylated baculovirus-produced IRS-1 exclusively on tyrosine residues.
1066 1385403 In addition, a phosphatidylinositol 3'-kinase associated with IRS-1 during insulin stimulation, and this association was more sensitive to insulin in CHO cells overexpressing the insulin receptor (CHO/IR cells), more responsive to insulin to CHO/IRS-1 cells, and both sensitive and responsive in CHO/IR/IRS-1 cells.
1067 1418289 Our recent studies show that antibodies to the mammalian hsp60 bind specifically to the 62 kDa protein located to insulin secretory granules and mitochondria of pancreatic beta cells of healthy mice [1].
1068 1425097 Insulin requirements from the 36th wk of gestation commonly decreased in women with IDDM, associated with longer duration of diabetes but did not carry any adverse prognostic indication for the infants.
1069 1425486 IL-1 is able to induce suppression of insulin release and biosynthesis in cultured rat pancreatic islets.
1070 1426762 With insulin stimulation, glucose transport is accelerated by translocating GLUT-4 transporters from an intracellular pool out to the T-tubule and SL membranes.
1071 1426762 Although the number of GLUT-4 transporters in the sarcolemma increases with exercise, neither insulin or its receptor is involved.
1072 1430198 Both chronic and acute insulin normalized LPL activity and immunoreactive LPL protein, while only chronic insulin corrected the levels of LPL mRNA.
1073 1280135 Since little is known about the regulation of these enzymes, we examined the effect of insulin and phorbol 12-myristate 13-acetate (PMA) treatment of well-differentiated rat hepatoma (Fao) cells on the expression of mRNAs encoding three major PTPase homologs in liver: PTPase1B, an intracellular enzyme with a single conserved PTPase domain, and two tandem-domain, transmembrane PTPases, known as LAR and LRP.
1074 1280135 In contrast, treatment with insulin or PMA had no significant effect of the abundance of mRNA encoding either LAR or LRP.
1075 1280574 Sulphonylureas lower hyperglycaemia by increasing insulin secretion and to a lesser degree potentiating insulin action on the liver and peripheral tissues. alpha-Glucosidase inhibitors are particularly useful as primary therapy for patients with mild to moderate hyperglycaemia and in those patients who may be at risk for hypoglycaemia or lactic acidosis.
1076 1280575 In several instances, it is suggested that insulin therapy be combined with sulphonylureas (essentially when residual insulin secretion is present), with metformin, or with alpha-glucosidase inhibitors.
1077 1360036 These findings suggest that the glucokinase mutation raises the set-point of pancreatic beta cells for glucose-induced insulin secretion, leading to abnormal glucose tolerance in some patients with late-onset NIDDM.
1078 1360726 Four groups were examined: untreated diabetic rats, insulin-treated diabetics and rats treated with an aldose reductase inhibitor (ponalrestat) given with and without insulin.
1079 1437714 Untreated insulin-deficient diabetes causes hyperphagia and neuroendocrine disturbances that may be partly mediated by increased hypothalamic activity of neuropeptide Y (NPY), a potent central appetite stimulant.
1080 1442030 This patient is the first case in Japan of Marfan syndrome associated with insulin-dependent diabetes mellitus, although the relation between Marfan syndrome and IDDM remains unclear.
1081 1445278 Compared with cells treated with insulin alone, adenosine in the presence of insulin increased the accessibility of GLUT4 to the extracellular photolabel by approximately 25%, consistent with its enhancement of insulin-stimulated glucose transport activity; the plasma membrane concentration of GLUT4 as assessed by Western blotting was unchanged.
1082 1446797 We have shown previously that insulin induces a rapid translocation of GLUT4s from an IM pool to the PM in rat skeletal muscle (6).
1083 1457766 Beta-blockers, calcium antagonists, and angiotensin-converting enzyme inhibitors have proved effective in reducing albumin excretion and postponing overt proteinuria in hypertensive and normotensive insulin-dependent diabetic patients with microalbuminuria.
1084 1457766 For insulin-dependent diabetic patients with microalbuminuria, the real aim of antihypertensive treatment is not to reduce urinary albumin excretion or to prevent its progression but to preserve renal function and to reduce the incidence of premature cardiovascular deaths.
1085 1459169 In spite of the reduction of the triglyceride concentrations and unchanged insulin levels, there was a significant increase of the activity of PAI-1 (+21%, P < 0.01) after MaxEPA suggesting a possible impairment of the fibrinolytic capacity.
1086 1334975 Nitric oxide has recently been implicated as the effector molecule that mediates IL-1 beta-induced inhibition of glucose-stimulated insulin secretion and beta-cell specific destruction.
1087 1334975 Pretreatment of beta-cells, purified by FACS with IL-1 beta results in a 40% inhibition of glucose-stimulated insulin secretion that is prevented by the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (NMMA).
1088 1460428 Mice bearing a tumor necrosis factor (TNF) alpha transgene controlled by an insulin promoter developed an increasingly severe lymphocytic insulitis, apparently resulting from the induction of endothelial changes with features similar to those observed in other places of intense lymphocytic traffic.
1089 1460846 Thus, it was surprising to find that fasting, refeeding, alloxan-induced diabetes, and insulin treatment had no effect on adipose tissue PEPCK mRNA in either rats or mice.
1090 1466160 Insulin infusion for 2 weeks, however, rapidly increased and overcorrected the number of osteoblasts, normalized serum osteocalcin and IGF-I concentrations but could not yet normalize bone mineralization.
1091 1466799 Interleukin-2 has also been identified by transgenic technology as a cytokine involved in the pathogenesis of insulin-dependent diabetes mellitus through the activation and stimulation of growth of autoreactive T cells.
1092 1468186 The metabolic effects of 52 weeks treatment with the aldose reductase inhibitor ponalrestat were examined in 32 diabetic patients (16 insulin treated) in a randomized, double-blind, placebo-controlled clinical trial.
1093 1468301 Preliminary evidence suggests that impaired GLUT4 expression in muscle is not the primary defect associated with insulin resistance.
1094 1468310 During the semitriathlon race, serum insulin, C-peptide, glucagon cortisol, growth hormone ACTH, prolactin, and plasma renin activity increased two- to ninefold, whereas serum testosterone fell.
1095 1468312 Insulin acutely increases glucose transport in muscle by selectively stimulating the recruitment of the GLUT4 transporter (but not GLUT1) from an intracellular pool to the plasma membrane.
1096 1468312 In these rats, insulin induced the mobilization of GLUT4 from the internal pool, but the incorporation of the transporter protein into the plasma membrane is diminished.
1097 1468454 We report a 2.3-year-old girl with complete lack of adenosine deaminase (ADA) activity who presented with severe atopic dermatitis and insulin-dependent diabetes mellitus but only mild recurrent infections.
1098 1476613 High dose i.p. insulin enhanced hepatic IGF-I mRNA levels (OD: 0.93 +/- 0.23) compared with diabetic rats (P < 0.01) and those given high dose s.c. insulin (P < 0.04), despite the blood glucose values being similar in the treated groups (i.p., 4.72 +/- 0.29 mmol/l; s.c., 3.32 +/- 0.03 mmol/l).
1099 1478377 Cleavage of proinsulin is mediated by at least two prohormone convertases (PC3/PC1 and PC2).
1100 1478377 GLUT 2 is necessary to reconstitute glucose-sensitive insulin secretion in pituitary tumour cells expressing a proinsulin cDNA.
1101 1480583 Model experiments with primary monolayer cultures of isolated islet cells have helped demonstrate a direct insulinotropic effect of STH, TRH, C-terminal tetrapeptide cholecystokinin, opioid peptides and blood plasma of patients with insulin-dependent diabetes mellitus.
1102 1482748 It is proposed that the decrease in GLUT4 levels is a protective mechanism, sparing skeletal muscle from gaining glucose and experiencing diabetic complications, albeit at the expense of becoming insulin resistant.
1103 1482782 To clarify this issue, we measured the width of skeletal-muscle basement membrane and erythrocyte aldose reductase activity in 27 insulin-dependent diabetic and 8 nondiabetic individuals.
1104 10122648 CSII may be a viable alternative to multiple daily injections for maintaining glycemic control in patients with IDDM who require intensive insulin therapy.
1105 1283175 It is proposed that, in the thyroid, hormonal (TSH, insulin, hydrocortisone, IGF-I) suppression of class I genes might be one means of preserving self-tolerance in the face of the hormone action to increase the expression of tissue specific genes such as thyroglobulin and thyroid peroxidase.
1106 1283442 Insulin rapidly decreases IGFBP-1 mRNA and IGFBP-1 transcription in rat hepatoma cells.
1107 1283442 The present study asks whether the increase in IGFBP-1 mRNA in diabetic rat liver reflects increased gene transcription, whether insulin decreases IGFBP-1 mRNA through a transcriptional or posttranscriptional mechanism, and whether this decrease is sufficiently rapid to account for the dynamic fluctuations in plasma IGFBP-1.
1108 1283442 Hepatic IGFBP-1 mRNA levels were 13.6 +/- 5.3-fold greater in diabetic than control liver and decreased to the low levels in nondiabetic controls within 1 h after insulin treatment.
1109 1283442 In run-on transcription assays, IGFBP-1 transcription was 12.6 +/- 1.5-fold greater in nuclei from diabetic than control liver and decreased to low control levels by 1 h after insulin injection.
1110 1283731 We found that at this dose level, galanin did not affect insulin secretion stimulated by glucose alone.
1111 1283731 In contrast, galanin clearly suppressed tolbutamide-stimulated insulin secretion.
1112 1283731 However, when active, galanin clearly inhibits insulin secretion also in the pig pancreas.
1113 1284142 Angiotensin-converting enzyme (ACE) inhibitors are established in the treatment of hypertension and heart failure; both conditions are complicated by resistance to insulin-mediated glucose disposal.
1114 1284142 There have been conflicting reports about the effects of ACE inhibitors on insulin sensitivity and glycemic control.
1115 1284142 Overall, there probably is a modest class effect of ACE inhibitors that enhances insulin-mediated glucose disposal; the mechanism of this effect is likely to be a combination of increased muscle blood flow, local renin-angiotensin system blockade, and elevated kinin levels.
1116 1295438 Insulin dependent or type 1 diabetes is an autoimmune disease with a strong genetic susceptibility linked to MHC and non MHC genes.
1117 1488874 The main objective of the study was to assess effects of long-term lowering of glucosylated hemoglobin (HbA1%) on neurosensory function in insulin-dependent diabetes.
1118 1285360 The changes in plasma gastrin-releasing peptide (GRP), arginine vasopressin (AVP), neuropeptide Y (NPY), corticotropin releasing hormone (CRH), galanin, ACTH, cortisol, delta sleep-inducing peptide (DSIP), adrenaline, noradrenaline and pancreatic polypeptide (PP) were measured after 5 and 15 minutes of acute insulin-induced moderate hypoglycaemia (2.0 mmol/l) in 10 patients with Type 1 diabetes mellitus with no autonomic neuropathy and in 10 healthy subjects.
1119 1300236 Genetic control of insulin dependent diabetes mellitus (IDDM) is mainly dependent on HLA genes in the major histocompatibility complex (MHC).
1120 1303676 In vitro studies have shown that they prevent the lymphocyte co-stimulatory activities of the cytokines IL-1 and IL-6 in a manner similar to that of cyclosporin A, and prevent the inhibitory effect of IL-1 on glucose-induced insulin production.
1121 1307056 The patient received a short insulin therapy and now he shows good metabolic control (normal glycosylated hemoglobin) with oral hypoglycemic treatment.
1122 1341919 We determined the serum concentrations of tumor necrosis factor (TNF) in 15 nondiabetic healthy subjects and in 36 insulin-dependent (type I) diabetic outpatients.
1123 7678005 Previous studies have documented that streptozotocin-induced insulin deficiency results in a marked decrease in adipose tissue GLUT4 glucose transporter mRNA levels (Sivitz, W.I., DeSautel, S.L., Kayano, T., Bell, G.I., and Pessin, J.E. (1989) Nature 340, 72-74).
1124 7678005 This rapid loss of GLUT4 expression did not correlate with changes in adipocyte cAMP levels and was not prevented by treatment of the cells with either insulin and/or PIA.
1125 7678005 These data demonstrate that the decrease in GLUT4 transcription induced by insulin deficiency in vivo predominantly results from an increase in intracellular cAMP levels.
1126 7678403 Galanin stimulated the high-affinity GTPase, over the concentration range in which it inhibits stimulated insulin secretion, to a maximal rate 80% greater than the basal rate.
1127 8094610 To look for a possible functional correlate to this finding basal and arginine stimulated plasma somatostatin and serum C peptide concentrations in eight insulin treated patients with cystic fibrosis and eight normal male controls were measured.
1128 8094610 Selective preservation of somatostatin secretion in patients with cystic fibrosis may further complicate pancreatic endocrine insufficiencies through paracrine inhibition of insulin and glucagon secretion.
1129 8380389 Using the glucose-responsive hamster beta-cell line (hamster insulin tumor cells), we examined the cellular mechanisms by which gastric inhibitory polypeptide (GIP) and glucagon-like peptide I(7-37) (GLP-I) potentiate glucose-stimulated insulin secretion.
1130 8380389 This study establishes that GIP and GLP-I potentiate glucose-stimulated insulin secretion by increasing extracellular Ca2+ influx through voltage-dependent Ca2+ channels.
1131 8380406 The insulin receptor possesses tyrosine kinase activity which is thought to mediate the biological effects of insulin upon target cells. pp120 is a liver-specific glycoprotein of apparent molecular size of 120 kDa that is phosphorylated on tyrosine residues by the receptors for insulin, insulin-like growth factor-I, and epidermal growth factor.
1132 8380562 Insulin treatment restored concentrations of tissue kallikrein activity, whereas the activities of tonin and other kallikrein-like proteinases were unchanged.
1133 8381211 Glucagon-like-peptide-1(7-37) (GLP-1) is an intestinally derived hormone that may be useful for the treatment of NIDDM because it acts in vivo to increase the level of circulating insulin, and thus lower the concentration of blood glucose.
1134 8419907 If 11.1 mM glucose perifusion in the presence of GIP was preceded by 5.5 mM glucose alone, the integrated insulin secretion/20 min above basal level was attenuated (1.46 +/- 0.10 vs. 0.37 +/- 0.03 ng; p < 0.01, n = 6), and withdrawal of GIP from the perifusion buffer resulted in the restoration of 11.1 mM glucose-stimulated insulin secretion (1.46 +/- 0.10 vs. 1.98 +/- 0.12 ng).
1135 8419907 These observations are consistent with a hypothesis that during a low glucose condition, GIP prevents the risk of hypoglycemia by suppressing insulin secretion, while during a high glucose load, glucose-induced insulin stimulation is potentiated by GIP, presumably to prevent hyperglycemia.
1136 8420806 Concordant increases of plasma PAI-1 and plasma IRI appear to reflect direct effects of insulin and proinsulin on the synthesis and secretion of PAI-1 by endothelial and liver cells as judged from results of studies in vitro.
1137 8423228 Both GIP and GLP-1 [7-36 amide] dose-dependently augmented insulin secretion (insulin, C-peptide) in both groups (P < 0.05).
1138 8425471 To explore whether this heterogeneity of response might be mediated by differential local insulin-like growth factor-I (IGF-I) gene regulation, we injected rats with ip saline, 65, 120, or 175 mg/kg streptozotocin (STZ).
1139 8425471 In summary: 1) hepatic IGF-I mRNAs are dramatically reduced, and renal IGF-I mRNAs are significantly increased soon after the onset of insulin-deficient diabetes in STZ-treated rats; 2) insulin therapy restores IGF-I mRNA levels toward normal; and 3) these changes in IGF-I mRNA content are specific and are not the result of hepatic or renal STZ toxicity.
1140 8425625 Insulin-like growth factor I receptor number appeared to be unaltered in both phases, whereas insulin receptor numbers and tyrosine kinase activity in the secretory phase were significantly increased.
1141 8425625 On the receptor level IGF-I signaling to human endometrium is not modulated during the menstrual cycle, whereas insulin binding and signaling are likely to be enhanced in the luteal phase.
1142 8425662 Glucagon, growth hormone, and pancreatic polypeptide levels increased briskly and significantly but were not different during the two insulin infusions.
1143 8425669 IAPP at 10(-7) M reduced insulin release by 32% from 7.1 (95% Cl 5.8-8.6) to 4.8 (3.0-7.5) fmol.min-1 x islet-1 (P = 0.046, n = 7).
1144 8425669 IAPP at 1.5 x 10(-6) M reduced insulin release by 62% from 6.5 (3.4-12.3) to 2.5 (1.4-4.4) fmol.min-1 x islet-1 (P = 0.001, n = 6).
1145 8425673 In this study, we sought to determine whether insulin stimulates the production and secretion of ET-1 as a possible basis for the association of hyperinsulinemia and vascular disease.
1146 8425673 We demonstrated that insulin significantly stimulates the gene expression and secretion of ET-1 from cultured BAEC, and that insulin increases ET-1 mRNA expressed in BBCEC.
1147 8425673 Insulin caused a maximal twofold inducement above control ET-1 mRNA expression in a dose-related fashion in BAEC.
1148 8425673 Increased ET-1 mRNA was seen after 4 h of incubation with insulin: the peak occurred at 6-8 h and persisted for 24 h.
1149 8426122 Glutamic acid decarboxylase (GAD) has been shown to be a target of autoantibodies in insulin-dependent diabetes (IDD).
1150 8095271 To confirm this hypothesis we investigated the T-cell activation trend, evaluating the surface expression of IL-2 receptor (CD25), transferrin (CD71), HLA class II (DR), and CD69 phenotypes after in vitro stimulation with phytohemagglutinin (PHA; 1 and 10 micrograms/ml) and concanavalin A (12.5 micrograms/ml) in six newly diagnosed Type I diabetics and six islet cell- and insulin autoantibody-positive first-degree relatives.
1151 8382698 A lysed preparation of isolated insulin secretory granules efficiently cleaved murine proopiomelanocortin (mPOMC) at physiologically important Lys-Arg processing sites.
1152 8382698 The in vitro processing of mPOMC by the insulin secretory granule endopeptidase activity reported here is in excellent agreement with the in vivo processing of this prohormone by a combination of PC2 and PC3, candidates of prohormone endpeptidase, in gene transfer studies with cells that express the regulated secretory pathway (Thomas, L., Leduc, R., Thorne, B.
1153 8383325 This combination of cytokines (IL-1 beta, TNF-alpha, and IFN-gamma) also influences insulin secretion by human islets.
1154 8383325 Higher concentrations (IL-1 beta at 75 units/ml, 3.5 nM TNF-alpha, and IFN-gamma at 750 units/ml) inhibit insulin secretion from human islets, and the inhibitory effect is prevented by NG-monomethyl-L-arginine.
1155 8384133 The tyrosine kinase activity of insulin receptors isolated from the control and NIDDM fibroblasts was similar (basal, 135 +/- 30 vs. 149 +/- 33; submaximal, 153 +/- 28 vs. 155 +/- 30; and maximal insulin, 191 +/- 45 vs. 213 +/- 48 dpm.mg protein-1 x min-1).
1156 8440711 In this study, we demonstrate in isolated rat pancreatic islets that the biosynthesis of PC3 was specifically stimulated by glucose relatively parallel to that of proinsulin.
1157 8440711 We suggest that co-ordinate stimulation of PC3 biosynthesis, along with that of its proinsulin substrate, elucidates an additional control point by which the mechanism of proprotein processing might be regulated.
1158 8445010 Insulin (100 microU/mL) decreased thrombin-induced platelet aggregation (washed platelets resuspended in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-Tyrode buffer).
1159 8446612 The glycolytic enzyme glucokinase plays an important role in the regulation of insulin secretion and recent studies have shown that mutations in the human glucokinase gene are a common cause of an autosomal dominant form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM) that has an onset often during childhood.
1160 8446851 The results indicate that lack of insulin action induces an anticoordinate change in gastrointestinal lipolytic enzymes, with decreases in pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase contents and an increase in pancreatic lipase content.
1161 8447318 This finding suggests that the insulin gene region contains a gene or genes contributing to IDDM susceptibility.
1162 8447376 Insulin treatment normalized renal ODC activity, whereas DFMO treatment totally inhibited the kidney ODC activity.
1163 8447376 Insulin treatment normalized both kidney weight and kidney ODC activity.
1164 8450080 Based upon their long-term medical records, 26 subjects were at baseline identified as having poorly controlled insulin-dependent diabetes (PIDD) with a mean blood glucose level of 12.5 mmol/l and a mean glycosylated hemoglobin (HBA1) level of 10.1%. 12 subjects were classified as having controlled insulin-dependent diabetes (CIDD) with a mean blood glucose level of 6.7 mmol/l and a mean HBA1 level of 9.2% at baseline.
1165 8453825 We examined the plasma protein binding of an acidic drug (warfarin bound to albumin) and a basic drug [lidocaine (lignocaine) bound to alpha 1-acid glycoprotein] in 15 patients with insulin-dependent diabetes mellitus (IDDM) and 15 matched controls.
1166 8454101 Our findings indicate that a gene on 4q, near the FABP2 and ANX5 loci, contributes to in vivo insulin action in Pima Indians.
1167 8456985 Also, diabetes decreased GLUT4 mRNA levels by 43%, and this effect was reversed by insulin therapy.
1168 8458530 In order to investigate these possibilities and to evaluate possible pathogenetic mechanisms, lipid composition (non-esterified and esterified cholesterol, triglycerides, phospholipids) of four VLDL subfractions of decreasing size (A: Svedberg flotation unit [Sf] > 400, B: Sf > 400, B: Sf 175-400, C: Sf 100-175, D: Sf 20-100), isolated by density gradient preparative ultracentrifugation, and plasma post-heparin lipolytic activity (lipoprotein lipase and hepatic lipase) were evaluated in 13 male normolipidaemic insulin-dependent diabetic patients in good glycaemic control (HbAlc 6.9 +/- 0.5%) (mean +/- SEM) and 9 male control subjects matched for age, body mass index and plasma lipid values.
1169 8460086 Moreover, ACE inhibitors and alpha blockers have been shown to improve insulin resistance in patients with noninsulin-dependent diabetes.
1170 7681983 Polymerase chain reaction analysis of mRNA from muscle biopsies detected exclusive or predominant expression of HIR-A in 13 patients with normal insulin sensitivity.
1171 8386184 Activation of phosphatidylinositol-3-kinase (PI3K) is one of the earliest postreceptor events in the insulin signaling pathway.
1172 8386184 Incubation of soleus muscles from lean mice with 50 nM insulin caused a 3-10-fold increase in antiphosphotyrosine-immunoprecipitable PI3K (antiPTyr-PI3K) activity within 2 min in muscle homogenates as well as both the cytosolic and membrane fractions.
1173 8386184 Insulin did not affect total PI3K activity.
1174 8467930 The aim of this study was to determine the effect of angiotensin-converting-enzyme inhibitor, alacepril, on insulin sensitivity in patients with essential hypertension (EHT).
1175 8471028 When insulin infusion was stopped, a 75% decrease in BAT UCP mRNA level and a 75% decrease in GLUT4 mRNA level were observed after 24 h, but UCP and GLUT4 concentrations did not decrease.
1176 8471028 This study shows that insulin plays an important role in the regulation of UCP and GLUT4 mRNA and protein concentrations in BAT.
1177 8473295 The predominant mechanism by which insulin activates glucose transport in muscle and adipose tissue is by affecting the redistribution of the facilitated hexose carriers, GLUT1 and GLUT4, from an intracellular site to the plasma membrane.
1178 8473295 Extrapolation to mammalian systems suggests that GLUT4 is responsible for virtually all of the hexose uptake in insulin-responsive targets, particularly in the presence of hormone.
1179 8474320 In normal subjects, plasma ANP levels increased significantly from 3.0 +/- 0.4 to 4.6 +/- 0.8 pmol/L during marked hyperglycemia, but did not change during euglycemia or moderate hyperglycemia despite higher insulin levels (P < .01, ANOVA).
1180 8475133 The nonglycosylated porcine PRL produced modest stimulation of cell division and insulin secretion from rat islets, but glycosylated porcine PRL had no significant effects.
1181 8475477 Plasminogen activator inhibitor-1 (PAI) activity, plasma insulin, glucose, cholesterol and triglyceride (TG) concentrations were determined in 32 Chinese diabetic patients (mean age 61.4 yr) and 41 healthy controls (mean age 64.5 yr) to establish the relationships between these parameters.
1182 8475477 Insulin, glucose, cholesterol and triglyceride levels were significantly higher in the diabetics, whereas no significant difference of PAI activity was noted between groups.
1183 8475477 PAI activity was not affected by the increase of plasma insulin, cholesterol, TG or glucose.
1184 8477877 Pancreatic tissue from 14 patients, 7 with Type 2 diabetes and 7 non-diabetic, were obtained at autopsy or surgery and studied for islet amyloid polypeptide expression by in situ hybridization and for presence of insulin and islet amyloid polypeptide by immunohistochemistry.
1185 8477949 These findings suggest that amylin may modulate the secretion of insulin from pancreatic beta-cells.
1186 8480468 In conclusion, at cystic fibrosis (a) insulin secretion is impaired even when glucose tolerance and insulin sensitivity are within the normal range, (b) the glucagon test gives valid estimates of residual beta cell function, (c) pancreatic polypeptide response to oral glucose is absent, (d) glucagon suppressibility decreases with decreasing glucose tolerance, and (e) the enteroinsular axis is intact.
1187 8482426 IGF-I also reduced plasma insulin concentrations.
1188 8482534 Transcription of the mouse beta-casein (beta CAS)-encoding gene (casB) is regulated by the synergistic actions of insulin, glucocorticoid and prolactin in the mammary gland (MG).
1189 7683646 Substitution of residues 48-50 with the analogous residues from human insulin (Thr-Ser-Ile) reduced binding to IGFBP-1, -5, and -6 more than 50-fold and to IGFBP-4 by 15-50-fold; binding to IGFBP-2 and -3 was reduced 6-12-fold.
1190 7683646 Substitution of Phe26 with Ser or Leu, which decreased binding to the IGF-I and insulin receptors, reduced binding to IGFBP-1 and -6 up to 80-fold, but had lesser effects on the other IGFBPs.
1191 7683660 Insulin induces the serine phosphorylation of the nucleolar protein nucleolin at subnanomolar concentrations in differentiated 3T3-442A cells.
1192 7683660 Insulin-like growth factor 1 mimics the action of insulin on dephosphorylation of nucleolin at nanomolar concentrations suggesting that the latter effect may be mediated by insulin-like growth factor 1 receptors.
1193 7683660 These data indicate that insulin regulates the phosphorylation/dephosphorylation of nucleolin, possibly via stimulation of casein kinase II, and this may play a role in regulation of the RNA efflux from nuclei.
1194 7683739 The liver is the primary source of IGFBP-1, and insulin is a major regulator of hepatic IGFBP-1 production.
1195 7683739 Using SRIF plus sequential graded insulin infusions, the threshold peripheral (= portal) plasma insulin concentration for IGFBP-1 suppression was between 65 and 172 pmol/L.
1196 8100786 It can be induced by as disparate means as tuberculin antigen administration, by interleukin-4 treatments, by transfer of T-cell lines generated in autologous mixed lymphocyte responses, and by immunization to insulin B-chain, whereas oral islet cell antigens, such as insulin, can delay diabetes onset in the NOD mouse.
1197 8317480 The association between HLA-DR and -DQ and insulin-dependent diabetes mellitus (IDDM) in a defined high-incidence area was analyzed in a total of 58 population-based patients, representing 77% of IDDM patients with age at onset below 16 years, and in 92 unrelated parents in control families without IDDM.
1198 8318452 The non-obese diabetic (NOD) mouse spontaneously develops a T cell-mediated autoimmune disease, sharing many features with human insulin-dependent diabetes mellitus (IDDM), leading to insulin-secreting beta cell destruction.
1199 8320278 In opposition to this view is the hypothesis that protein kinase C is not activated by insulin and, more importantly, may be responsible for attenuation of the insulin signal.
1200 8325447 After an acute treatment with insulin, the proportions of GLUT4 and GLUT1 at the cell surface were increased to 49 and 37% of the total, respectively.
1201 8325447 The chronic insulin treatment was associated with a very low proportion of GLUT4 (25% of the total) at the cell surface.
1202 8390376 Insulin induced hydrolysis of PIG/PMIG and generation of IG, DAG, and AAG in a dose-dependent manner.
1203 8391325 Alterations of liver membrane phospholipase C activity in NIDDM, therefore, may reflect diabetic pathology other than the insulin resistance associated with this disease.
1204 7686917 The fibroblast insulin receptor content was within the normal range, but both basal and insulin-stimulated tyrosine kinase activity in fibroblast extracts were markedly decreased compared to those in extracts of fibroblasts from nondiabetic subjects.
1205 7687210 The effects of insulin and/or tryptophan (Try) administration on Try, serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA) in raphe nuclei and hypothalamus and serum levels of large neutral amino acids [Try, valine, isoleucine, leucine, tyrosine and phenylalanine, (LNAA)] was investigated in diabetic rats. 2.
1206 7687807 Nocturnal serum IGFBP-1 increased and correlated inversely with insulin in both studies.
1207 7688320 A high glucose or fructose diet, or insulin administration caused a similar magnitude of increase in the level of L-type pyruvate kinase mRNA in the liver of Wistar fatty rats and their lean littermates.
1208 7688320 However, the induction of glucokinase mRNA and repression of phosphoenolpyruvate carboxykinase mRNA by dietary glucose or insulin were impaired in the fatty rats, whereas fructose caused a similar decrease in phosphoenolpyruvate carboxykinase mRNA in both types of rats.
1209 7688320 These results indicate that the regulation of gene expression of glucokinase and phosphoenolpyruvate carboxykinase, but not of L-type pyruvate kinase, by insulin is impaired in the liver of the Wistar fatty rat.
1210 7688368 The insulin-like growth factor-binding proteins (IGFBPs) are a family of six proteins that modulate the biological activity of IGF-I and IGF-II and determine their bioavailability to tissues.
1211 7688368 Insulin rapidly decreased IGFBP-1 transcription in the absence of cycloheximide (> 50% inhibition in 20 min) and caused a similar decrease in cells pretreated with cycloheximide.
1212 7688368 Similar results were observed with a second protein synthesis inhibitor, anisomycin, which also prevented the insulin-induced decrease in IGFBP-1 mRNA without abolishing the insulin-induced inhibition of IGFBP-1 transcription.
1213 7688368 These results suggest that although insulin decreases IGFBP-1 gene transcription in the presence of protein synthesis inhibitors, IGFBP-1 mRNA levels are maintained because of stabilization of the mRNA.
1214 7688368 Stabilization was demonstrated directly in actinomycin D-treated cells, where the t1/2 of IGFBP-1 mRNA increased from approximately 2 to approximately 20 h in the presence of cycloheximide; insulin did not affect IGFBP-1 mRNA turnover.
1215 8325892 Glucokinase plays a key role in the regulation of glucose metabolism in insulin-secreting pancreatic beta-cells and in the liver.
1216 8325952 Insulin-stimulated glucose uptake rate in peripheral tissue was decreased by 41% (P < 0.01) in NIDDM patients compared to healthy subjects, whereas no significant differences could be shown in the abundance of total GLUT4 protein per DNA or GLUT4 messenger RNA (mRNA) per DNA among the 2 groups in muscle biopsies obtained in the basal state.
1217 8325952 In conclusion, 4 h of insulin infusion causing supraphysiological serum insulin levels modulates the expression of GLUT4 in skeletal muscle from healthy subjects, with divergent effects at protein and mRNA levels.
1218 8325952 Factors other than total GLUT4 protein content of muscle play a role in determining insulin-stimulated glucose uptake in human skeletal muscle.
1219 8325960 Decreased sex hormone-binding globulin (SHBG; an indirect measure of androgenicity) is associated with hyperinsulinemia and insulin resistance.
1220 8335171 When diabetic rats were treated for 20 h with s.c. insulin, there was decreased neuropeptide Y mRNA in the arcuate nucleus.
1221 8335171 We conclude that neuropeptide Y mRNA in the arcuate nucleus is responsive to small changes in circulating insulin levels and the response occurs within 20 h.
1222 8335181 These findings suggest a mechanism for persistent islet amyloid polypeptide secretion and amyloid accumulation when regulated insulin release is impaired as in Type 2 (non-insulin-dependent) diabetes mellitus and insulinomas.
1223 8340422 A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin.
1224 8340422 Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate 32P-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK.
1225 7690030 Photolabeling intact cells with the impermeant, exofacial photolabel 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 - yloxy)-2-propylamine in the continuous presence of insulin revealed that K+ depletion had no effect on the GLUT4 externalization rate but halved the rate of internalization.
1226 8102504 The pancreatic content of insulin did not differ between non-diabetic and GK rats, whereas the content of somatostatin was increased by 56% (P < 0.025) in GK glands.
1227 8349037 Inositol phosphoglycan mimicked the action of insulin on both forms of the enzyme from adult hepatocytes, whereas in fetal cells insulin did not change, and purified inositol phosphoglycan reduced the activities of glycogen phosphorylase.
1228 8349040 For example, it has been shown that glucosamine is more potent than glucose in inducing insulin resistance in cultured adipocytes and in regulating the transcription of the growth factor transforming growth factor alpha in smooth muscle cells.
1229 8349045 In HIR-cells, which express GLUT1 and not GLUT4, basal and insulin-stimulated glucose transport were unaffected by glucosamine, but glycogen synthesis was markedly inhibited.
1230 8349045 Insulin-stimulated activation of protein kinases (MAP and S6) was unaffected, and the fractional velocity and apparent total activity of glycogen synthase was increased in glucosamine-treated HIR-cells.
1231 8349045 Glucosamine-induced insulin resistance of glucose transport appears to be restricted to GLUT4-expressing cells, i.e., skeletal muscle and adipocytes; it may reflect impaired translocation of GLUT4 to the plasmalemma.
1232 8349666 These data show, for the first time, that insulin has little, if any, effect on the rate constant for GLUT4 endocytosis, but instead, primarily increases the rate constant for exocytosis.
1233 8352437 Insulin binding and insulin responsiveness are altered by dietary fat-induced changes in the fatty acid composition of the adipocyte plasma membrane.
1234 8354339 Animal experiments demonstrate that interleukin-1 beta (IL-1 beta) is beta-cell cytotoxic in vitro and inhibits insulin secretion in vivo.
1235 8365355 This increase in receptor density probably resulted from the stimulation of receptor protein production, because insulin caused a maximal 2.3 +/- 0.3 (+/- SEM) fold increase in the ETA receptor mRNA expressed in cultured VSMC by 4 h.
1236 8372101 Serum levels of prolactin decreased in all diabetic groups and insulin failed to restore these levels to those of control animals.
1237 8372111 Insulin reduces adipsin expression in vitro and is negatively correlated with adipsin expression in vivo.
1238 8372111 Because bovine somatotropin (bST) opposes many actions of insulin and can reduce body fat content, we tested the hypothesis that bST enhances adipsin expression.
1239 8105694 To determine if increased secretion of amylin can be implicated in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) in vitro and in vivo, we studied its relationships to insulin in insulin-resistant rats with and without NIDDM.
1240 8213069 Here we report that the activity of eucaryotic initiation factor-2 (eIF-2), a protein that participates in the regulation of a rate-limiting initiation step of protein synthesis, transiently decreases following insulin-induced severe hypoglycemia in the rat brain neocortex.
1241 8213069 We conclude that severe insulin-induced hypoglycemia induces a stress response in neurons in the recovery phase, including inhibition of protein synthesis initiation, depression of eIF-2 activity, and a delayed and prolonged expression of HSP 72 in surviving neurons.
1242 8216350 The effect of the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (dCF) on the development of insulin-dependent diabetes mellitus (IDDM) was assessed in the BB Wistar rat.
1243 8218870 It was found that binding of soluble insulin in the subcutaneous tissue is negligible for U-40 and U-100 strengths.
1244 7504175 We identified some of the tyrosine residues of IRS-1 that undergo insulin-stimulated phosphorylation by the purified insulin receptor and in intact cells during insulin stimulation.
1245 7504175 These results extend the notion that IRS-1 is a multisite docking protein that engages various downstream regulatory elements during insulin signal transmission.
1246 7694822 Both liver message and serum IGFBP-2 were reduced to control levels with insulin therapy. 4.
1247 7694822 We report here that in addition to its affects on IGFBP-2, insulin is involved in the regulation of IGFBP-3 expression.
1248 7694841 Circulating levels and hepatic expression of insulin-like growth factor-binding protein-1 (IGFBP-1) are increased in insulin-deficient streptozotocin (STZ)-diabetic rats.
1249 7694841 Glucocorticoids stimulate and insulin suppresses hepatocellular expression of IGFBP-1 in vitro.
1250 7694841 We asked whether increased IGFBP-1 expression in STZ-diabetic animals is due to an effect of insulin deficiency per se or whether insulin deficiency represents a permissive state where glucocorticoids may play an important role in the regulation of IGFBP-1 and other circulating peptides involved in the modulation of IGF bioactivity.
1251 8242903 We previously reported that nonspecific immunomodulations with a streptococcal preparation (OK-432), an inducer of tumor necrosis factor (TNF), or with recombinant TNF prevented development of insulin-dependent diabetes mellitus (IDDM) in animal models (NOD mice and BB rats).
1252 8243324 GAD is present outside the brain, and pancreatic islet GAD is believed to be a target of autoimmunity in insulin-dependent diabetes mellitus.
1253 8243832 Short-term treatment of desensitized adipocytes with glimepiride or insulin reduced GLUT4 phosphorylation by approximately 70 and 25%, respectively, in both fractions.
1254 8245375 Adjustment for body weight, insulin dose, and physical activity using multiple regression analysis did not change the relationship between HbA1 and intakes of energy and fat.
1255 8253016 On day 16 the EGF concentration in milk was significantly increased in insulin-treated rats, as compared to controls [2.66 (1.40-5.08) nM vs. 1.98 (1.04-3.16) nM].
1256 7505214 Studies in normal man and rodents have demonstrated that the expression of the dominant glucose transporter in skeletal muscle, GLUT4, is regulated by insulin at supraphysiological circulating levels.
1257 7505214 The present study was designed to determine whether intensified insulin replacement therapy for 24 h given to patients with Type 1 diabetes in poor metabolic control was associated with an adaptive regulation of GLUT4 mRNA and protein levels in vastus lateralis muscle.
1258 7505518 Galanin inhibits insulin secretion and has been proposed to function as a sympathetic neurotransmitter in the endocrine pancreas in some species, for example in the dog.
1259 7505909 Insulin treatment normalizes glycemia levels, partially counteracts P0 mRNA increase at both stages of diabetes and delays MBP mRNA increase present only in chronic animals.
1260 7903584 Adaptation to hypoxia caused hypoglycemia, activated insulin biosynthesis, changed glucagon and somatostatin synthesis and secretion.
1261 8261243 To determine whether the increased PAI-1, known to be associated with accelerated coronary artery disease in non-diabetic subjects, is a consequence of direct effects of insulin on endothelial cells, we performed the present study with primary cultures of human aortic endothelial cells.
1262 8261243 Insulin at pharmacologic concentrations did not alter either PAI-1 or t-PA production by the human aortic endothelial cells, although insulin stimulated PAI-1 synthesis in human hepatoma (Hep G2) cells as expected.
1263 8279544 Moreover, in vivo insulin exposure neither for 30 min nor for 4 h had any impact on the content of GLUT-4 protein in plasma membranes.
1264 8279544 With the use of the same methodology, antibody, and achieving the same degree of plasma membrane purification and recovery, we found, however, that intraperitoneal administration of insulin to 7-wk-old rats within 30 min increased the content of GLUT-4 protein more than twofold (P < 0.01) in the plasma membrane from red gastrocnemius and soleus muscle.
1265 8279544 With this technique, we were unable to show evidence for a regulatory effect of insulin on the plasma membrane level of GLUT-4 protein in human muscle.
1266 8281728 GHBP, expressed as a percentage of (125I)GH bound, was determined in 33 patients with Type 1 diabetes (M/F = 19/14, 12.3 +/- 0.4 years) before (day 0), after 5 days (day 5) and after 3 months (month 3) of insulin therapy.
1267 8281728 Thus, (1) circulating GHBP is low in newly diagnosed patients with Type 1 diabetes, and increases after 3 months of insulin therapy but does not normalize and (2) the severity of biochemical derangement and residual beta-cell function at diagnosis may determine GHBP status and its recovery.
1268 8284270 Insulin-deficient diabetes and food deprivation markedly increase hypothalamic NPY and NPY mRNA levels, suggesting increased activity of NPYergic pathways in the hypothalamus, which could account for hyperphagia and neuroendocrine changes in these conditions.
1269 8111613 Amylin also reduces insulin secretion and induces insulin resistance.
1270 8111860 Insulin also stimulates the synthesis of glucokinase and moderates the degree of gluconeogenesis.
1271 8117990 Chronic acidosis and alkalosis decrease insulin secretion and stimulates corticotropin secretion.
1272 8119455 To add new insights to the question, changes in lipid peroxidation products and activities of three antioxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD) in maternal red blood cells haemolysates were evaluated in pregnant women with insulin-dependent diabetes mellitus (IDDM-PW) and in healthy pregnant women (HPW).
1273 8122031 Insulin or PLC increased protein kinase C (PKC) activity in the membrane fraction in C, but not in DM.
1274 8125072 GLP-1 hormone is released into the circulation from intestinal L cells in response to meals and is the most potent incretin hormone known; GLP-1 and GIP appear to account for most, if not all, of the intestinal incretin effect in the augmentation of glucose-stimulated insulin secretion.
1275 8125072 Because of the discoveries that GLP-1 stimulates both secretion and production of insulin, and that the actions of GLP-1 are entirely glucose-dependent, GLP-1 may provide unique advantages over the sulfonylurea drugs in the treatment of NIDDM.
1276 8130360 Plasma renin concentration did not differ between control, diabetic, and insulin-treated diabetic groups.
1277 8130360 Angiotensinogen mRNA levels were significantly lower in the livers and adrenals of diabetic rats in comparison to those in controls and insulin-treated diabetic rats, whereas angiotensinogen mRNA levels in the brain remained unaltered.
1278 8299479 However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies.
1279 8304913 Although compensatory hyperinsulinaemia may prevent the development of NIDDM in insulin-resistant individuals, there is substantial evidence that insulin resistance and/or hyperinsulinaemia is associated with higher plasma concentrations of triglyceride, uric acid and plasminogen activator inhibitor 1 and with lower HDL cholesterol concentrations.
1280 8306194 The reduced thyroid hormone concentrations observed in untreated streptozotocin-diabetic rats were restored towards control levels in animals receiving the lowest dose of insulin (1 U/day), whereas higher doses of insulin were required to more closely restore euglycemia and lower glycated hemoglobin.
1281 8307253 Pharmacological doses of islet amyloid polypeptide have been shown to inhibit insulin secretion as well as insulin action on peripheral tissues (insulin resistance).
1282 8307253 To examine the role of islet amyloid polypeptide in the pathogenesis of Type 2 diabetes, we have generated transgenic mice with the gene encoding either human islet amyloid polypeptide (which can form amyloid) or rat islet amyloid polypeptide, under control of an insulin promoter.
1283 8307253 This suggests that insulin resistance is not induced by chronic hypersecretion of islet amyloid polypeptide.
1284 8314199 In the present study, it was investigated whether the amorphous zinc insulin Semilente can be used to control fasting hyperglycemia in IDDM patients.
1285 7511786 Culture with 10(-9) M insulin lowered IGFBP-1 gene transcription 50% below control levels (10-11 M) but did not affect IGF-I gene transcription; 10(-6) M insulin raised IGF-I gene transcription 2-fold.
1286 7511786 Similarly, 3-6 h were required for stimulation of IGF-I gene transcription by insulin, but a 40% decrease in IGFBP-1 gene transcription could be detected within 15 min after adding 10(-6) M insulin, and suppression of IGFBP-1 transcription by insulin was unaffected by the presence of cycloheximide.
1287 7514335 Hepatic expression of IGFBP-1 is regulated at the level of gene transcription by insulin in a dominant negative fashion, while glucocorticoids and cAMP analogues exert positive effects on hepatocellular IGFBP-1 mRNA.
1288 8003613 The expression of a major autoantigen, the beta-cell specific enzyme glutamic acid decarboxylase (GAD), is glucose-dependent in vitro and correlated to insulin release in vitro.
1289 8055784 The observed increase in the amount of degraded insulin may reflect an increase in the activity of insulinase, an enzyme bound to the cell membrane and partly present in the cytoplasm.
1290 8055819 Blood serum fructosamine and blood glycosylated hemoglobin (HbA1) concentrations were determined in 47 children with newly diagnosed insulin-dependent diabetes during their first stay in the hospital.
1291 8077324 The aim of the present study was to determine if differing concentrations of insulin can modify the counterregulatory response to equivalent fixed hypoglycemia in insulin-dependent-diabetic subjects (IDDM).
1292 8077324 In response to hypoglycemia, plasma levels of epinephrine, norepinephrine, cortisol, GH, and pancreatic polypeptide increased similarly during both insulin infusions.
1293 8138185 To determine whether alteration in serum antioxidant status is related to the increased oxidative stress as a cause of diabetic angiopathy, we measured both the antioxidant activity (AOA) and total peroxyl radical-trapping antioxidant parameter (TRAP), and their component individual antioxidants in serum of children with insulin-dependent diabetes mellitus (IDDM).
1294 8149699 In the type 2 population serum butyrylcholinesterase activity was also correlated with insulin sensitivity (r = -0.51, P < 0.001). 4.
1295 8155257 Furthermore, in these mice, insulin autoantibodies (IAA) cross-react with retroviral protein p73 (the IAP gag gene product), suggesting molecular mimicry between insulin and p73.
1296 8155257 We therefore investigated whether IAA and insulin antibodies (IA) associated with human IDDM cross-reacted with p73.
1297 8155257 Approximately 65% of sera which bound insulin by ELISA also bound p73.
1298 8155257 Only one sample negative for insulin binding was positive for p73 binding.
1299 7507068 IGFBP-1 concentrations were suppressed by > 50% in two rat models of insulin resistance.
1300 7507826 The effects of several classes of agents on interleukin-1 beta (IL-1 beta)-induced suppression of insulin secretion, beta-cell NAD levels, and beta-cell viability were examined.
1301 7507826 After overnight incubation of isolated rat islets with 15 U/ml IL-1 beta and 11 mM glucose, sequential hourly insulin secretory responses to the same glucose concentration, 22 mM glucose, and 22 mM glucose plus forskolin were severely inhibited to 10-37% of the control value.
1302 7712683 Therefore, in our study naloxone infusion seems to have beta-endorphin-like effects in non-diabetic obese subjects by increasing their glycemic levels, with no evidence of expected insulin decrease.
1303 8250456 Metabolic control in patients with extreme insulin resistance is improved after using IGF-1.
1304 8262308 To determine whether this delay was related to transcapillary transport of insulin, we determined increments in serum insulin levels, glucose disposal rates (GDR), and insulin receptor (IR) kinase activity measured during continuous infusions of insulin (40 and 120 mU.m-2.min-1) administered to 8 nondiabetic males; similar studies were done at 1,200.m-2.min-1 in 2 of the subjects.
1305 8262324 Insulin-like growth factor I and aldosterone, on the other hand, also increased glucose consumption but brought about an enhancement of only type IV collagen production, suggesting that the two collagens are independently regulated.
1306 8275942 This study investigates whether the expression of TNF alpha and its receptors is modulated during drug treatment to reduce insulin resistance.
1307 8275944 Insulin treatment of control rats demonstrated a marked 8-fold transient increase (15 min) in c-fos mRNA in white adipose tissue, which returns to basal levels by 5 h.
1308 8275944 By contrast, insulin treatment resulted in only a small increase in c-jun mRNA levels in both adipose tissue and cardiac muscle.
1309 8275944 Similarly, the expression of c-jun mRNA was only slightly responsive to insulin in these tissues from streptozocin-induced insulin-deficient diabetic rats.
1310 8275944 However, insulin treatment of insulin-deficient diabetic rats resulted in a prolonged increase in c-fos message levels in adipose tissue without any significant change in the time course of c-fos mRNA induction/repression in cardiac muscle.
1311 8275944 These data demonstrate that in contrast to c-jun, c-fos is transiently increased in both cardiac muscle and adipose tissue by insulin treatment.
1312 8275944 Furthermore, transrepression of the c-fos gene is specifically attenuated in adipose tissue of insulin-deficient diabetic rats, but not in cardiac muscle.
1313 8276864 Subsequently, AA was observed to alter the ability of the GLUT4 transporter to respond to insulin and mediate a significant enhancement of glucose uptake.
1314 8276864 The results presented in this study indicate that AA can partially mimic the effects of both tumor necrosis factor-alpha and insulin which, when chronically supplied to 3T3-L1 adipocytes, also down-regulate GLUT4 gene expression.
1315 8277951 Islet amyloid polypeptide (IAPP), a hormonal factor secreted from the pancreatic beta cells, reduces insulin sensitivity in vivo and glycogen synthesis in vitro.
1316 8278373 Since this form of GAD appears to be an integral membrane protein and is presumed to have extracellular domains exposed, it seems reasonable to suggest that membrane GAD is more likely than soluble GAD to be involved in the pathogenesis of insulin-dependent diabetes and related autoimmune disorders such as stiff-man syndrome.
1317 8281664 We and others have hypothesized that the increased PAI-1 may contribute to acceleration of atherosclerosis in this condition and in other states characterized by insulin resistance as well.
1318 8281664 To assess this possibility directly, this study was performed to identify potential direct effects of proinsulin and proinsulin split products on synthesis of PAI-1 in liver cells, thought to be the major source of circulating PAI-1 in vivo.
1319 8281664 Our results are consistent with the hypothesis that precursors of insulin (proinsulin and proinsulin split products), known to be present in relatively high concentrations in plasma in patients with NIDDM and conditions characterized by insulin resistance, may directly stimulate PAI-1 synthesis, thereby attenuating fibrinolysis and accelerating atherogenesis.
1320 8288045 We examined the association of body mass index (BMI), waist-to-hip ratio (WHR), sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-SO4), and estradiol with insulin concentrations and whole-body glucose disposal in 87 men from a population-based study in Kuopio, Finland.
1321 8288045 SHBG and total and free testosterone were significantly associated with insulin concentrations and total and nonoxidative glucose disposal but not with glucose oxidation.
1322 8289665 The newly discovered intestinal hormone, glucagon-like peptide-1 (GLP-1) (proglucagon 78-107amide), stimulates insulin secretion and inhibits glucagon secretion in man and may therefore be anticipated to influence hepatic glucose production.
1323 8294562 Insulin does not appear to be involved in the expression of lymphocyte GH or POMC.
1324 8294562 The administration of insulin to the diabetic animals had no significant effect on the expression of GH or POMC by the immune cells.
1325 11271269 The long-term effect of pancreatic and kidney transplantation (spkt) on blood viscosity, lipid metabolism and skin microcirculation in insulin-dependent diabetes mellitus (IDDM) was studied because impaired rheological properties of blood may play a role in the development of diabetic micro- and macroangiopathy. 46 IDDM-patients (16 f/30 m; 23 +/- 34 y mean duration of diabetes; 60 +/- 14 mos mean follow up period) underwent spkt (Gr.I: n = 28) or solitary kidney (Gr.II: n = 18) transplantation, and were compared with healthy controls (C).
1326 7510305 In a substrate-sufficient state, e.g. after oral glucose, IGFBP-1 and -2 show opposite acute responses to IGF-I, and IGF-I has an apparent acute insulin-like effect on IGFBP-1 concentrations that differs from its longer term effect.
1327 7510884 Phosphorylation of glucose to glucose 6-phosphate by glucokinase (GK; EC 2.7.1.2) serves as a glucose-sensing mechanism for regulating insulin secretion in beta cells.
1328 7907998 Thus, somatostatin may inhibit insulin gene transcription by insulin gene-specific effects as well as more general effects on gene expression.
1329 7907998 Both epinephrine and somatostatin inhibited expression of the human insulin-CAT reporter gene in a concentration-dependent manner that paralleled inhibition of insulin secretion.
1330 8116999 Patients with insulin-dependent diabetes mellitus have reduced endogenous IGF-I production, and studies are in progress to determine whether treatment with IGF-I in addition to insulin may improve their metabolic/anabolic status.
1331 8120522 Tissue plasminogen activator antigen measured after venous occlusion showed a significant reduction whilst plasminogen activator inhibitor 1 activity was 26.0 +/- 9.8 IU ml-1 on oral treatment and 18.2 +/- 4.7 IU ml-1 on insulin treatment (NS).
1332 8125759 The EC50 for glucose transport was similar in endothelial cells and pericytes (3.94 to 0.48 mM versus 2.24 to 0.69 mM) and was consistent with the EC50 previously reported for GLUT1 transporters on other cells, as was the observation that insulin did not acutely stimulate glucose transport in either cell type.
1333 8130898 High doses of IL-1 are cytotoxic to beta cells and strongly inhibit insulin release; high-dose IL-1 plus TNF acts synergically to suppress further the insulin release.
1334 8130898 In contrast, we observed that the predominant effect of low-dose IL-1 and TNF when administered separately was the stimulation of insulin release.
1335 8130898 We therefore asked whether the combination of low-dose IL-1 plus TNF would act synergistically to stimulate or suppress insulin release.
1336 8134187 These results indicate that insulin deficiency in lactating rats causes a decrease in the lactational performance and in the EGF content of milk.
1337 8135807 Following insulin treatment, GLUT4 increased in F25 and decreased in F35.
1338 8138054 PC3 cleaves proinsulin first to generate a proinsulin conversion intermediate that is the preferred substrate of PC2.
1339 8138054 Both PC2 and PC3 activities are influenced by Ca2+ and pH, but the more stringent Ca2+ and pH requirements of PC3 suggest it as the most likely enzyme to regulate proinsulin conversion, as well as initiate it.
1340 8138062 Insulin-stimulated glucose uptake in individual skeletal muscles was not altered until day 7 after STZ, and the magnitudes of decreases in skeletal muscle insulin action on days 7 and 14 were not fully accounted for by the decreases in GLUT4 protein level measured from the same muscles.
1341 8141164 Finally, insulin potentiates the effects of other agonists (eg, thromboxane A2, angiotensin II) on vascular contraction and cell growth.
1342 8141419 Arterial pressure during ANP infusion decreased similarly in control; diabetic, and insulin-treated diabetic rats (by 7.6 +/- 1.6, 9.6 +/- 1.9, and 8.2 +/- 2% respectively; all P < 0.002).
1343 8141419 ANP infusion increased plasma ANP levels to the same extent in the three groups, whereas plasma guanosine 3',5'-cyclic monophosphate (cGMP) was significantly less in diabetic as compared with control and insulin-treated diabetic rats.
1344 7512496 Expression and secretion of IGFBP-3 were hormonally responsive and strongly correlated (r = 0.79; P < 0.001), with 2- to 3-fold stimulation by added insulin or IGF-I (both P < 0.05), but not by added GH alone.
1345 7512573 In the present study we have 1) assessed how differences in insulin and GH status between obese patients with noninsulin-dependent diabetes mellitus (NIDDM) and healthy obese (OB) and nonobese (NOB) subjects are associated with different responses of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) to fasting, and 2) determined whether the IGF-I response to fasting in healthy subjects is secondary to changes in IGFBP-3.
1346 7512573 Insulin-resistant NIDDM patients, with high basal glucose and insulin, normal IGFBP-1, and low GH, had decreased prefasting serum IGF-I concentrations, similar to the values in fasted body mass index- and age-matched OB subjects.
1347 7512956 In differentiated 3T3-F442A adipocytes, insulin stimulated rapid and transient phosphorylation of c-Jun.
1348 7512956 Insulin also stimulated phosphorylation of c-Fos and several Fos-related proteins (pp72, pp45, and pp39) as indicated by precipitation with anti-c-Fos antibody following exposure to denaturating conditions.
1349 7512956 This is associated with changes in AP-1-mediated gene expression in vivo, suggesting that AP-1 phosphorylation by insulin plays a role in insulin-regulated gene expression.
1350 7513716 Insulin-like growth factor-I (IGF-I) in serum is predominantly bound in a ternary complex, consisting of IGF peptide, IGF-binding protein-3 (IGFBP-3), and an acid-labile subunit, or a binary complex, consisting of IGF peptide and any of the six IGFBPs.
1351 7909309 The study of 230 diabetic mothers along with their newborn babies has shown that foetal macrosomia is associated with two specific genomic sites: phosphoglucomutase locus 1 (PGM1)-Rhesus blood group (Rh) linkage group (chromosome 1) and HindIII restriction fragment length polymorphism (RFLP) linked to insulin-like growth factor 1 (IGF1) (chromosome 12).
1352 8150226 We investigated whether a defect of insulin-dependent glucose transporter (GLUT 4) translocation might contribute to the pathogenesis of the insulin-resistant state. fa/fa rats, lean controls (Fa/Fa) as well as normal Wistar rats were injected intraperitoneally with insulin and were killed after 2 or 20 min, respectively.
1353 8150226 Insulin induced an approximately two-fold increase of GLUT 4 in a plasma membrane and transverse tubule enriched fraction and a decrease in the low density enriched membrane fraction in all three groups of rats.
1354 8150226 The data suggest that skeletal muscle insulin resistance of obese Zucker rats is not associated with a lack of GLUT 4 translocation.
1355 8157682 These studies indicate that GLUT-2 expression confers both a high and low affinity glucose-stimulated insulin secretion response to intermediate passage RIN cells.
1356 8158209 While the total or relative deficiency of insulin causes diabetes, the possible disorders due to deficiency of nerve growth factor have not been clearly defined.
1357 8161942 In all the areas studied, acute hyperglycemia caused an increase in the activity of acetylcholinesterase, the degradative enzyme of cholinergic system, whereas insulin administration reversed this effect.
1358 8168650 In two subjects with glucokinase mutations, which resulted in only a small reduction in enzymatic activity, the decrease in insulin secretion was directly proportional to the decrease in GK flux predicted using a Michaelis-Menten model for both mutant and wild-type glucokinase.
1359 8168650 However, in four subjects with glucokinase mutations, which resulted in severe reductions in enzymatic activity, insulin secretion was reduced compared with control subjects but less than predicted.
1360 8175660 Insulin stimulated PP-1 activity (40-80% increase over basal) in a time (t1/2 approximately 5 min)- and dose (EC50 approximately 0.1 nM)-dependent manner.
1361 8175660 Insulin activation of PP-1 was accompanied by a corresponding inhibition in PP-2A activity.
1362 8175660 Treatment of cells with a cAMP agonist (SpcAMP) completely blocked activation of PP-1 by insulin and diminished insulin-stimulated phosphorylation of the 160-kDa protein.
1363 8175660 From these studies, we conclude that insulin activates PP-1 in L6 cells by increasing the phosphorylation of its regulatory subunit.
1364 8177048 We examined the association of sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-SO4), and estradiol to glucose and insulin concentrations before and during an oral glucose tolerance test in 178 men from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease.
1365 8177049 A protein kinase A (PKA) inhibitor (H8 in low concentrations) abolished cAMP and PTH effects, but not those of insulin, whereas the PKC inhibitors (sphingosine and high concentrations of H8) did abolish the effects of insulin.
1366 7514190 An exposure of 144 h to IL-1 beta plus IFN-gamma plus TNF-alpha increased NO production and decreased both glucose-induced insulin release and insulin content.
1367 7514190 Inhibitors of NO generation, aminoguanidine or NG-nitro-L-arginine, blocked this cytokine-induced NO generation, but did not prevent the suppressive effect of IL-1 beta plus IFN-gamma plus TNF-alpha on insulin release and content.
1368 7514206 More than 95% of IGF-I circulates bound to binding proteins (IGFBPs); of these IGFBP-1 is of particular interest as it is inversely regulated by insulin and is thought to inhibit the action of IGF-I and IGF-II.
1369 7514206 Elevated IGFBP-1 levels have been associated with an inhibition of serum IGF-I bioactivity in children with insulin-dependent diabetes.
1370 7514513 After each treatment period (4 weeks), serum profiles of GH, IGF-I, IGF binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), glucose, insulin, non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate, alanine, lactate and glucagon were measured for 37 hours after GH injection (3 IU/m2 at 1900 hour).
1371 7515882 The PP-1 stimulation by TPA was comparable to stimulation by insulin (t1/2 = 1 min and EC50 = 5 nM) with a maximum effect in 5 min.
1372 7515882 Insulin and TPA also stimulated MAPK (> 2-fold increase over basal, with myelin basic protein as a substrate).
1373 7515882 ML-9, a myosin light chain kinase inhibitor, blocked the effects of insulin and TPA on both MAPK and PP-1 activation.
1374 7515882 In these cells subsequent effects of insulin on MAPK and PP-1 activation were blocked, without an effect on basal enzyme levels.
1375 7515882 These inhibitors completely prevented insulin and TPA stimulation of MAPK and PP-1 and blocked insulin-induced translocation of PKC to the plasma membranes.
1376 7515882 We conclude that PKC plays an important role in insulin stimulation of PP-1 via the activation of MAPK cascade.
1377 8181185 In these studies the effect of IL-10 was determined on three parameters of diabetes: The development of hyperglycemia, the development of insulitis, and the production of insulin by beta cells.
1378 8181185 Histopathology performed on pancreatic tissue demonstrated that treatment with IL-10 reduced the severity of insulitis, prevented cellular infiltration of islet cells, and promoted normal insulin production by beta cells.
1379 8182159 Glucagon-like peptide 1 [7-36 amide] (GLP-1) has been shown to enhance insulin secretion in healthy and type II diabetic humans, and to increase glucose disposal in type I diabetic patients.
1380 8187319 It has been proposed that low IGF-I levels and reduced IGF-I bioactivity may lead to elevated GH levels in adolescents with insulin dependent diabetes (IDDM).
1381 8187319 We have therefore studied the effects of human recombinant insulin-like growth factor I (rhIGF-I) administration on GH levels and GH secretion in adolescents with IDDM.
1382 8192664 In this system, insulin stimulated an 8.6-fold increase in 3-O-methylglucose glucose transport, while photolabelled GLUT4 increased 8-fold.
1383 8194659 The hypothesis to be tested in this study was that defects in the islet beta-cell GLP-1 receptor gene contribute to the impaired glucose-regulated insulin secretion of non-insulin-dependent diabetes mellitus (NIDDM).
1384 8194661 NPY administration also resulted in a pronounced increase in the in vivo insulin-stimulated glucose uptake by adipose tissue but in a marked decrease in uptake by eight different muscle types.
1385 8194662 Five to 50 mM of NA dose-dependently reduced inhibition of accumulated islet insulin release induced by 150 pg/ml of IL-1 beta.
1386 8195122 In order to study how alpha beta half-receptors interact to form the insulin-binding site, we cotransfected NIH-3T3 cells with two insulin receptor cDNA constructs: a truncated insulin receptor lacking the C-terminal 43 amino acids (delta 43) and the full-length Leu323 mutant receptor.
1387 8196603 During insulin stimulation, GRB-2 binds to the phosphorylated Y895VNI motif of IRS-1.
1388 8196603 The Shc-GRB-2 complex formed during insulin stimulation is a possible mediator of p21ras and MAP kinase activation in IRS-1-deficient 32-D cells.
1389 8196603 Interestingly, IRS-1, but not IRS-1F-895, enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors.
1390 8197147 Chronic exposure of adipocytes to low concentrations of TNF-alpha strongly inhibits insulin-stimulated glucose uptake.
1391 8197147 Concurrently, TNF-alpha treatment causes a moderate decrease in the insulin-stimulated autophosphorylation of the insulin receptor (IR) and a dramatic decrease in the phosphorylation of IR substrate 1, the major substrate of the IR in vivo.
1392 8197147 These results show that TNF-alpha directly interferes with the signaling of insulin through its receptor and consequently blocks biological actions of insulin.
1393 8201968 Moreover, insulin-treated nSTZ rats exhibited decreased amylin to insulin molar ratios compared with saline-treated nSTZ rats (P < .05), which had the same levels as normal rats.
1394 8202531 Insulin stimulates a 4.3-fold recruitment of transfected epitope-tagged GLUT4 to the cell surface.
1395 8203977 The effect of chronic pancreatitis and insulin on the expression of the hepatic facilitative glucose transporter protein (GLUT-2) was determined in rats.
1396 8203977 The suppression of HGP production by insulin was compared with changes in GLUT-2 in the membrane fraction of liver biopsies obtained before and after hormone perfusion.
1397 8203977 In contrast, rats with chronic pancreatitis (n = 6) showed no suppression of HGP during 1.2-nM insulin perfusion, and an increase in GLUT-2 (+20 +/- 6%) after insulin perfusion (p < 0.02 vs. sham).
1398 8203977 Insulin suppresses glucagon-stimulated HGP in normal and sham-operated rats, and this reduction in HGP is associated with a decrease in the membrane-bound quantity of GLUT-2.
1399 8203977 In chronic pancreatitis, insulin suppression of HGP is absent, and this is accompanied by an increase in GLUT-2 in the hepatocyte membrane.
1400 8203977 The authors conclude that the insulin-mediated change in the level of hepatocyte GLUT-2 is impaired in chronic pancreatitis, and may contribute to the altered glucose metabolism observed commonly in this disease.
1401 8204669 STZ-diabetes increased renal aldose reductase gene expression in a manner that was not reversible by insulin but had no effect on gene expression in the brain, testes and muscle.
1402 8205465 The calcium antagonists and ACE inhibitors have better metabolic profiles and the latter reduce insulin resistance.
1403 8206589 It is possible that the reduced magnesium content of the high-fructose commercial diet used in some studies may play a role in these abnormalities because it is known that magnesium deficiency can produce insulin insensitivity and increased angiotensin II action in humans.
1404 7516850 There is a growing body of evidence that the insulin-like growth factors (IGF-I and IGF-II) are dynamically involved in the regulation of glucose homeostasis, with one of their binding proteins, IGFBP-1, playing a counterregulatory role.
1405 7517895 GLP-1 (glucagon-like peptide 1 (7-36) amide) plays an important role in the regulation of insulin secretion and proinsulin gene expression of pancreatic beta-cells.
1406 7912209 The islet-1 (Isl-1) gene encodes a protein that binds to the enhancer region of the insulin gene.
1407 7912625 When the insulin response to glucose was suppressed with somatostatin and diazoxide, metformin improved glucose disposal to a similar extent to that in rats with a normal insulin response.
1408 7913115 The analysis of the correlation between class I overexpression, residual insulin, and insulitis suggests that the first event is the increase of HLA class I expression.
1409 8010960 Binding of IGF-II was approx. 25% of that of insulin at 1 nM concentrations of both hormones.
1410 8010960 In order to explore which receptor mediated the IGF-II effect, we compared glucose uptake induced by IGF-II and two IGF-II analogues: [Leu27]IGF-II, with high affinity for the IGF-II/Man 6-P receptor but markedly reduced affinity for the IGF-I and insulin receptors, and [Arg54,Arg55]IGF-II was similar to that of IGF-II, whereas [Leu27]IGF-II had a very diminished effect.
1411 8013751 We sought to explore the emerging concept that malonyl-CoA generation, with concomitant suppression of mitochondrial carnitine palmitoyltransferase I (CPT I), represents an important component of glucose-stimulated insulin secretion (GSIS) by the pancreatic beta-cell (Prentki M, Vischer S, Glennon MC, Regazzi R, Deeney JT, Corkey BE: Malonyl-CoA and long-chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion.
1412 8013761 Furthermore, although both FGF-2 and HGF/SF increased the total insulin content of the cultures, only HGF/SF increased the insulin content per DNA.
1413 8013761 Blocking of the IGF-I receptor inhibited ICC formation but did not affect their insulin content.
1414 8020983 Expression of reg is markedly increased in regenerating islets and decreased when insulin gene expression is inhibited.
1415 8022753 Interleukin-1, tumor necrosis factor, and interleukin-6 inhibit insulin release and may be cytotoxic to isolated pancreatic islets.
1416 7519260 The human insulin domains, signal peptide, B-chain, C-peptide, and A-chain, were highly expressed in Escherichia coli as recombinant proteins N-terminally fused to glutathione-S-transferase and a histidine-hexapeptide.
1417 7520127 The differentiation of 3T3-F442A cells was characterized by a 13-fold increase in insulin receptor protein, a 9-fold increase in IRS-1, and a 10- and 4.5-fold increase in their insulin-stimulated phosphorylation, respectively.
1418 7520127 Chronic insulin treatment also produced a 30% decrease in PI 3-kinase protein levels and a approximately 50% decrease in the association/activation between IRS-1/PI 3-kinase.
1419 7914371 The regulation of IP3R-3 levels by glucose, diabetes, and refeeding may allow the beta cell to adjust the insulin secretory response to changing physiological conditions.
1420 8030746 Interleukin-6 (IL-6) is thought to be involved in the pathogenesis of autoimmune insulin-dependent diabetes mellitus.
1421 8034738 In this study we have investigated the targeting signal of the 65-kD isoform of glutamic acid decarboxylase (GAD65), a major autoantigen in two autoimmune diseases: Stiff-Man syndrome and insulin-dependent diabetes mellitus.
1422 8036284 In normal subjects during euglycemia, GLP-1(7-37) stimulated insulin release, whereas GIP did not.
1423 8036284 GIP at a dose of 1, 2 or 4 pmol/kg/min augmented the 90-120 min insulin response by 69, 841 and 920 pmol/l, while GLP-1(7-37), at a dose of 1.5 pmol/kg/min augmented the insulin response by 2106 pmol/l.
1424 8036284 In the diabetic subjects, GIP had no effect, while GLP-1(7-37) augmented the insulin response by 929 pmol/l.
1425 8037667 Insulin treatment in vivo had no effect on the microsomal membrane content of small GTP-binding proteins, but significantly decreased the 24 kDa species in GLUT4-enriched vesicles by 36 +/- 5% (n = 3).
1426 8037667 Western-blot analysis of microsomal membranes with a panel of antisera against rab GTP-binding proteins indicated the presence of rab4A, with a molecular mass of 24 kDa, whereas rab1A, rab2 and rab6 were not observed. rab4A was barely detectable in GLUT4-enriched vesicles; however, insulin produced an extensive shift of rab4A from the cytosol and the microsomal fraction to the plasma membrane with a parallel increase in GLUT4.
1427 8039433 No specific abnormalities of the insulin receptor kinase activity were revealed in insulin-dependent diabetes (IDDM) or in common NIDDM.
1428 8039596 Insulin and IGF-I vascular effects were not inhibited by BQ123, an endothelin (ET) antagonist that blocked ET-1 enhancement of AVP response.
1429 8040280 In summary, the beta-cell sensitivity for glucose was increased in these normoglycemic insulin resistant rats by an enhanced catalytic activity of glucokinase.
1430 8040280 We have identified a regulatory system for glucokinase in the beta-cell which entails variable catalytic activity of the enzyme, is modulated in response to variations in whole-body insulin sensitivity, and is not dependent on sustained changes in the plasma glucose level.
1431 8043899 Interestingly, a significant inverse correlation was found between TCGF activity and the required dose of insulin only in group A (r = -0.66; P < 0.05).
1432 8045959 Smaller iv doses (250 micrograms/kg) of IGF-I were ineffective in acutely lowering serum glucose or inducing sustained insulin sensitivity.
1433 8048502 Phenylarsine oxide (PAO) has previously been shown to inhibit insulin-stimulated glucose transport without affecting insulin binding and tyrosine kinase activity of insulin receptor (S.
1434 8048502 This study examines the effect of PAO on insulin's ability to activate adipocyte protein phosphatase 1 (PP-1) and dephosphorylate GLUT-4, the insulin-sensitive glucose transporter.
1435 8048502 In particulate fractions, insulin stimulated PP-1 activity (40% increase over basal with phosphorylase a) in a time- and dose-dependent manner (half-maximal effect of 0.89 nM in 1 min).
1436 8048502 Insulin did not alter cytosolic PP-1 activity.
1437 8048502 With GLUT-4 as a substrate, insulin caused more than twofold stimulation of particulate PP-1 activity.
1438 8048502 In addition, PAO significantly increased GLUT-4 phosphorylation, blocked insulin-stimulated dephosphorylation, and partially diminished insulin-stimulated translocation of GLUT-4.
1439 8048502 We conclude that PAO may interfere with the components of insulin signal transduction pathways that lead to the activation of PP-1 and this may be responsible for the observed inhibition in insulin action.
1440 8049217 However, they fail to undergo insulin-stimulated internalization, do not regulate the phosphorylation of insulin receptor substrate 1, and are unable to mediate an insulin-stimulated increase in DNA synthesis and c-jun and c-fos expression.
1441 8056130 In non-obese diabetic subjects, men with Type 1 diabetes have higher HDL-cholesterol than those with Type 2 diabetes, possibly due to the action of peripheral insulin on lipoprotein lipase activity, while in women, HDL-cholesterol concentrations were similar in Type 1 and Type 2 subjects possibly because of lowered lipatic lipase activity in Type 2 women which offsets the increased lipoprotein lipase activity of the Type 1 women.
1442 8056188 Insulin-dependent diabetes mellitus (IDDM) is associated with class II molecules of the MHC on chromosome 6, in particular HLA-DR and -DQ alleles, but a pathogenic role for TNF-alpha in the class III region of the MHC has also been implied.
1443 8058065 The role of insulin receptor tyrosine kinase activity in stimulation of intracellular enzymes linked to insulin action [phosphatidylinositol 3-kinase (PtdIns 3-kinase), microtubule-associated protein (MAP) kinase, and S6 kinases] was studied in Chinese hamster ovary cells which overexpress wild type human insulin receptors, receptors with reduced kinase activity due to substitution of Phe for Tyr1146 (single-Phe), Tyr1150,1151 (double-Phe), and Tyr1146,1150,1151 (triple-Phe), or kinase-inactive receptors with a substitution of Ala for Lys1018 in the ATP binding site (A1018).
1444 8058065 Overexpression of the wild type insulin receptor increased both maximal insulin receptor substrate-1-associated and total insulin-stimulated PtdIns 3-kinase activity, as well as S6 and MAP kinase activities 2.0- to 3.6-fold.
1445 7523002 This difference in the IGFBP-1 response in the presence of a similar glucose response suggests that in Type 1 diabetes there may be different sensitivities to the actions of exogenous insulin on IGFBP-1 regulation.
1446 7523453 These results demonstrate that TNF-alpha participates in obesity-related systemic insulin resistance by inhibiting the IR tyrosine kinase in the two tissues mainly responsible for insulin-stimulated glucose uptake: muscle and fat.
1447 7523562 Insulin-dependent diabetes mellitus (IDDM) during puberty is associated with a reduction in circulating concentrations of insulin-like growth factor-I (IGF-I) and low IGF bioactivity.
1448 7918678 Triggering of autoimmunity in insulin-dependent diabetes was linked to dietary bovine serum albumin (BSA).
1449 7924776 These results demonstrate that insulin-induced hypoglycemia increases muscle sympathetic neural outflow in IDDM and control subjects.
1450 7924880 In one of the subjects, a girl, the titers of ICA increased in parallel with a decrease in insulin secretion before the development of overt IDDM and declined thereafter.
1451 7926284 It remains unclear whether decreased pancreatic glucokinase activity will produce defects of insulin secretion similar to those observed in NIDDM.
1452 7926284 Glucosamine (5 mmol/l) reduced glucokinase activity in islet homogenate and diminished the insulin response to glucose (200 mg/dl) by isolated islets, whereas the response to arginine (20 mmol/l at 100 mg/dl glucose) was unaffected.
1453 7926286 The percentage increase in insulin-stimulated transport in T3-treated muscles is similar to the increase in GLUT4 protein content, whereas the percentage change in basal transport greatly exceeds the change in GLUT4.
1454 7926286 Thus, increased insulin-stimulated glucose transport in T3-treated muscle can be accounted for by the induction of GLUT4 protein.
1455 7926294 In previous studies, we have failed to reveal mutations in the coding regions of the muscle-specific glycogen synthase gene and the three genes that encode the catalytic subunits of protein phosphatase 1 (PP1) as frequent causes of insulin resistance.
1456 7926294 Because the glycogen-associated regulatory subunit of protein phosphatase 1 (PP1 G-subunit) plays a key role in the insulin stimulation of glycogen synthesis and the activity of PP1 is decreased in insulin-resistant subjects, we have now cloned the human G-subunit cDNA to search for abnormalities in the corresponding gene (designated PPP1R3 in the human genome nomenclature) in patients with NIDDM.
1457 7926300 On a cellular level, TNF-alpha is a potent inhibitor of the insulin-stimulated tyrosine phosphorylations on the beta-chain of the insulin receptor and insulin receptor substrate-1, suggesting a defect at or near the tyrosine kinase activity of the insulin receptor.
1458 7926350 These results suggest that sulphonylureas and insulin induce suppression of thrombin-induced activation of phospholipase C, which mediates hydrolysis of PIP and PIP2 and production of PA, which leads to inhibition of platelet aggregation.
1459 7929614 While amylin induces insulin resistance in skeletal muscle, it does not oppose insulin action in fat and may therefore favor fuel deposition in this tissue.
1460 7929617 This suggests that chronic overproduction of islet amyloid polypeptide "per se" does not cause insulin resistance.
1461 8087095 Patients with gestational diabetes mellitus (GDM) are heterogeneous; adipocyte GLUT 4 levels are either normal or markedly reduced but all patients exhibit abnormalities in GLUT 4 subcellular distribution and insulin-mediated translocation. 3.
1462 8088710 An analysis of the structural conformation of insulin suggested that an inversion of amino acids B28 and B29 in the C-terminus of the B chain could yield an insulin analog with a faster onset of biological action.
1463 8088711 Studies performed under hyperglycemic conditions showed that IGF-I inhibited glucose-stimulated insulin secretion, but that this inhibitory effect was partially overcome by increasing the hyperglycemic stimulus.
1464 8088711 Moreover, despite the decrease in insulin secretion, glucose disposal was accelerated by IGF-I.
1465 8091976 Inadequate blood sugar control in children with insulin-dependent diabetes mellitus (IDDM) sometimes results in low insulin-like growth factor-I (IGF-I) and sluggish height growth.
1466 7525123 Octreotide treatment, in addition to reducing GH, IGF-I and insulin levels, is associated with an increase in IGFBP-1 concentrations in patients with acromegaly, and it is suggested that the rise in serum IGFBP-1 is a consequence of the decrease in insulin secretion.
1467 7530059 Using NG-nitro-L-arginine methyl ester, an inhibitor of both the constitutive and the cytokine inducible forms of nitric oxide synthase, and aminoguanidine, a preferential inhibitor of the inducible form of nitric oxide synthase, we investigated the impact of inhibiting nitric oxide production on food-intake, body weight and temperature, blood glucose, plasma insulin, glucagon, corticosterone and leukocyte- and differential-counts in normal rats injected once daily for 5 days with interleukin 1 beta (IL-1 beta) (0.8 microgram/rat = 4.0 micrograms/kg).
1468 7530343 The levels of substance P and calcitonin gene-related peptide in diabetic sciatic nerve were significantly lowered by approximately 50% and 28%, respectively, compared with aged matched controls and insulin-treated diabetic rats (P < 0.01) for both peptides and both comparisons).
1469 7530592 We used ring segments of the rabbit facial artery mounted in a myograph to test the hypothesis that potentiation of NE-induced tone by insulin may be related to activation of protein kinase C (PKC) and tyrosine kinase (TK).
1470 7532054 We have examined the regulation of IGFBP-2 expression by IGF-I and insulin in 293 cells, a cell line derived from human embryonic kidney.
1471 7532054 IGFBP-2 levels were increased 6 to 7-fold following incubation with IGF-I, IGF-II or insulin for 48 h.
1472 7532054 Biosynthetic labeling of quiescent 293 cells using [35S]cysteine indicated that incubation with insulin or IGF-I for 24 h increased the synthesis of total cell proteins (predominantly intracellular) and IGFBP-2 (predominantly secreted) to a similar extent (2- to 4-fold).
1473 7828080 The study involved a group of insulin-dependent BB Wor rats showing marked variations in metabolic control, assessed by the level of glycosylated hemoglobin (gHb).
1474 7833679 In further similar studies, CD8+ cells from patients with Graves' disease (GD) are induced normally in response to glutamic acid decarboxylase-65 (GAD-65), the putative beta cell antigen important in insulin-dependent diabetes mellitus (IDDM), but significantly less to synthetic TSH receptor (TSHR).
1475 7840858 ICA69 is a recently cloned pancreatic islet protein proposed as a potential target of autoimmunity in insulin dependent diabetes mellitus (IDDM).
1476 7846765 Although the level of GLUT2 is frequently reduced in animal models of type II diabetes, GLUT2 does not limit glucose metabolism in beta cells and does not appear to regulate glucose induction of insulin secretion.
1477 7851872 Earlier studies have demonstrated decreased levels of circulating Insulin-Like Growth Factor-I (IGF-I) in patients with NIDDM and IDDM (Yde 1969; Rieu and Binoux 1985), with a return to normal in those diabetics who achieve improved metabolic control (Rieu and Binoux 1985; Ameil, Sherwin, Hintz, Gertner, Press and Tamborlane 1984) following insulin therapy.
1478 7854353 The malic enzyme (ME) gene, which encodes an important lipogenic enzyme, was used to investigate insulin regulation of gene expression.
1479 7857436 In this study we determine the erythropoietin levels and hematocrit in 22 women with preterm labor, 21 with insulin-dependent diabetes, 22 with preeclampsia, and 20 with normal gestation.
1480 7858104 We determined the HLA-DQB1 genotypes by denaturing gradient gel electrophoresis (DGGE) and/or sequence-specific primers (SSP) techniques to assess the possible interactions between INS and HLA.
1481 7533311 Insulin treatment partially ameliorated the decrease in mRNA levels for MMP-1 and MMP-3 and the increase in those for TIMP-1 in the glomeruli of diabetic rats.
1482 7535696 IGFBP-1 is antagonistic to the insulin-like and growth promoting effects of IGF-I, and IGFBP-3 holds IGFs in the circulation by associating with IGFs and an acid labile subunit to form a ternary complex.
1483 7695875 IDDM is characterized by progressive beta-cell destruction which leads to complete insulin deficiency; at the time of diagnosis 80-90% of beta cells have been destroyed.
1484 7705017 There is suggestive evidence that amylin acts physiologically in an autocrine manner within the islet to restrain insulin secretion, but conversely there is little indication that this action of amylin plays any role in the development of NIDDM.
1485 7705017 The potential exists for the development of amylin antagonists as pharmacological agents to enhance insulin secretion in NIDDM but antagonism of systematic CGRP would need to be avoided.
1486 7705199 We examined effect of insulin or 12-O-tetradecanoyl phorbol 13-acetate (TPA) on the subcellular redistribution of protein kinase C isoforms in rat adipocytes.
1487 7705199 These results suggest that (a) insulin and phorbol esters similarly stimulate the translocation of each PKC isoform except for PKC-zeta, and (b) the translocation of both nPKCs and cPKCs occurs during insulin and TPA actions in rat adipocytes.
1488 7705986 Plasma adrenaline, noradrenaline and pancreatic polypeptide increased significantly in both groups during hypoglycemia and the insulin levels never exceeded 50 mUl-1.
1489 7865456 To examine the role of IL-2 in the regulation of peripheral tolerance we produced transgenic mice in which the expression of murine IL-2 was directed by the rat insulin II promoter.
1490 7875052 One hundred pM TGF-beta stimulated insulin release during 0.5-24 h of incubation in the presence of 5.5 mM glucose, but not after 48 h; 1 nM TGF-beta also stimulated insulin release up to 2 h of exposure, but the effect was not seen after 6 h of exposure.
1491 7875052 When cells were incubated with 25 mM glucose for 24 h, 100 pM TGF-beta significantly inhibited glucose-stimulated insulin release, whereas insulin release was not altered at 0 or 2.8 mM glucose.
1492 7875052 On the contrary, forskolin- (10 microM) and tolbutamide- (40 microM) induced insulin release were not affected by TGF-beta.
1493 7875052 TGF-beta affected neither the cell growth nor the cellular insulin content.
1494 7882825 GDM patients who required insulin during pregnancy possessed a significantly higher frequency of A33, DR2, DR9, and BF-S phenotypes than control subjects.
1495 7895951 To examine the effect of acute hyperglycaemia on nerve conduction eight non-diabetic men (20-49 years of age) with no signs of peripheral neuropathy were studied before and after 3 h of hyperglycaemic clamping (plasma glucose approximately 15 mmol/l), while insulin secretion was suppressed by somatostatin [Study 1].
1496 7648787 Diabetes caused hyperglycaemia (2.5-fold), a marked decrease (4.5-fold) in liver glycogen, a 4-fold increase in the glucose-6-phosphatase activity and significant decrease in plasma insulin levels and protein kinase activity.
1497 7648795 Insulin treatment of platelets is associated with increased prostaglandin E1-stimulated adenylyl cyclase activity and decreased platelet aggregation.
1498 7648795 Because non-insulin dependent (Type II) diabetes mellitus is associated with hyperinsulinemia, we sought to determine the effect of insulin treatment in vivo and in vitro upon stimulation of platelet adenylyl cyclase by prostaglandin E1.
1499 7648795 Pre-incubation of platelet-rich plasma with 0.7 nM insulin resulted in a 62% increase in prostaglandin E1 (2 microM)-stimulated cAMP accumulation (p < 0.005).
1500 7664533 These findings suggested that thyroid hormone and glucagon-cyclic AMP suppress, and glibenclamide increases the GKmRNA level in cultured rat islet cells, and that insulin, cyclic GMP and vanadate differentially affect glucokinase gene expression in pancreatic islet cells and in the liver.
1501 7756973 Glucose-induced insulin secretion is inhibited by the cytokines interleukin-1 beta (IL-1 beta), interleukin-6 and tumour necrosis factor alpha (TNF) when combined with IL-1 beta in cultured rat islets, by IL-1 beta, TNF and interferon gamma in mouse islets, and by combined treatment of IL-1 beta, TNF and interferon gamma in human islets.
1502 7767864 Therefore, thyroid hormones may interact with some other factor(s) in this acute, insulin-deficient model of diabetes to selectively regulate functional, heparin-releasable lipoprotein lipase activity in perfused hearts.
1503 9098456 The segregation of these alleles has been associated with levels of TNF alpha or TNF beta production in systemic lupus erythematosis (SLE), insulin-dependent diabetes mellitus (IDDM) and in healthy control individuals.
1504 7530649 Insulin-like growth factor-II (IGF-II) binds to 150-kilodalton (kDa) protein complexes in adult rat serum that have higher affinity for IGF-II than IGF-I.
1505 7530759 Although TNF+LPS induce iNOS expression and inhibit insulin secretion by intact islets, this combination does not induce the expression of iNOS by beta or alpha cells purified by fluorescence activated cell sorting (Facs).
1506 7530759 In contrast, IL-1 beta induces the expression of iNOS and also inhibits insulin secretion by both intact islets and Facs-purified beta cells, whereas TNF+LPS have no inhibitory effects on insulin secretion by purified beta cells.
1507 7530759 Evidence suggests that TNF+LPS inhibit insulin secretion from islets by stimulating the release of IL-1 which subsequently induces the expression of iNOS by beta cells.
1508 7530759 The IL-1 receptor antagonist protein completely prevents TNF+LPS-induced inhibition of insulin secretion and attenuates nitrite formation from islets, and neutralization of IL-1 with antisera specific for IL-1 alpha and IL-1 beta attenuates TNF+LPS-induced nitrite formation by islets.
1509 7530759 Local release of IL-1 within islets appears to be required for TNF+LPS-induced inhibition of insulin secretion because TNF+LPS do not stimulate nitrite formation from islets physically separated into individual cells.
1510 7532577 Glutamic acid decarboxylase (GAD), a target of both autoantibodies and autoreactive T-cells in insulin-dependent diabetes (IDD), exists as two homologous forms, GAD65 and GAD67.
1511 7813818 We studied tissue factor pathway inhibitor (TFPI) activity in insulin-dependent diabetes mellitus (IDDM) patients without macro-or microvascular complications, before and after intravenous administration of heparin, in comparison with age-matched control subjects.
1512 7813819 Previously, we have demonstrated that somatostatin mediates all of its inhibitory effects on glucose-induced insulin secretion from the HIT-T15 cell through pertussis toxin-sensitive G-proteins and that the membrane fraction of this clonal line of pancreatic beta-cells contains six such proteins: G(i) alpha 1, G(i) alpha 2, G(i) alpha 3, and three forms of G(o) alpha.
1513 7814644 Our data demonstrate that overexpression of Glut4 protein in muscle increases basal as well as insulin-stimulated whole body glucose disposal.
1514 7822300 In this study, we examined the distribution of protein serine/threonine phosphatase-1 (PP-1) and analyzed the effect of insulin on PP-1 and its mechanism of activation in freshly isolated rat adipocytes.
1515 7822300 Insulin rapidly stimulated PF PP-1 in a time- and dose-dependent manner (maximum stimulation at 5 min with 4 nM insulin).
1516 7822300 Insulin stimulated PP-1G (120% over basal levels) without affecting the other forms of PP-1 in the PF.
1517 7822300 The insulin effect on MAP kinase and PP-1 activation was blocked by a GTP antagonist, guanyl-5'-yl thiophosphate.
1518 7822300 We conclude that insulin rapidly activates a membrane-associated PP-1 in adipocytes, which may be similar to rabbit skeletal muscle PP-1G, and the activation is mediated by p21Ras/MAP kinase pathway.
1519 7828304 To define the possible presence of such an axis, this study was designed to determine whether insulin, its precursors, or both increase the concentrations of PAI-1 in rabbits in vivo.
1520 7828304 Plasma PAI-1 activity increased 3.8-fold with proinsulin (P = .002) and 3.6-fold with insulin (P = .002).
1521 7828304 As judged from changes in mRNA in tissues, proinsulin and insulin increased PAI-1 gene expression within 3 hours by 2.1- and 2.1-fold, respectively, in aorta (P = .025 each) and by 1.9- and 2.4-fold in liver (P = .015 and P = .001), with return of values to baseline within 24 hours (n = 4 experiments in each case).
1522 7830033 The main aim of this study was to examine the effects of an angiotensin converting inhibitor, enalapril, and an alpha-1 (alpha-1) antagonist, doxazosin, on albumin excretion, renal haemodynamics and tubular function in insulin-dependent diabetes mellitus patients with nephropathy.
1523 7835294 Numerous in vivo and in vitro studies have shown the effects of interleukin-1 (IL-1) on insulin and glucagon secretion.
1524 7840166 In the present studies, we have examined the acute and chronic effects of insulin on angiotensin II (ANG II)-induced aldosterone synthesis in cultured normal and adenomatous human adrenal glomerulosa cells.
1525 7840166 Short-term insulin treatment (1.5 h) resulted in inhibition of ANG II-induced aldosterone synthesis.
1526 7840166 The acute inhibitory effects of insulin were in part mediated by inhibition of the 12-lipoxygenase pathway.
1527 7840166 The chronic stimulatory effect of insulin seemed to be due at least in part to the upregulation of cytochrome P-450 side-chain cleavage enzyme levels.
1528 7840315 We hypothesized that corticosteroids and insulin might serve as interacting, reciprocal signals for energy balance, acting on energy acquisition, in part through their effects on hypothalamic NPY, as well as on energy stores.
1529 7840315 Glucocorticoids stimulated and insulin inhibited NPY mRNA and food intake.
1530 7840315 The effects of corticosterone and insulin on food intake may be mediated, in part, through regulation of hypothalamic NPY synthesis and secretion.
1531 7533733 Insulin reversed the inhibitory effects of ANG II on renin in normal rats, but it blunted the effect of ANG II in diabetic rats.
1532 7534289 We investigated whether Crk is a target for the insulin-like growth factor I (IGF-I) receptor tyrosine kinase.
1533 7535266 Inhibition of adenylyl cyclase activity is one of at least four mechanisms by which the neuropeptide galanin inhibits insulin secretion from pancreatic beta-cells.
1534 7535266 In a membrane preparation of the insulin-secreting cell line RINm5F, a maximally effective concentration of galanin inhibited forskolin-stimulated adenylyl cyclase activity by 30%.
1535 7536170 However, insulin treatment had no effect on glomerular hypertrophy or urinary albumin excretion.
1536 7536170 However, insulin treatment for 3 weeks with induction of euglycaemia diminishes the renal hypertrophy but has no effect on glomerular volume or urinary albumin excretion.
1537 7536171 Interleukin-1 beta (IL-1 beta) has been suggested to mediate beta-cell destruction in insulin-dependent diabetes mellitus (IDDM) by inducing nitric oxide production.
1538 7536205 Before insulin therapy, serum IGF-I, IGF-II, IGF-binding protein-3 (IGFBP-3), and GH-binding protein (GHBP) levels were significantly decreased, whereas IGFBP-1 and cortisol were significantly increased in diabetic children compared to those in an age-, sex-, and stage of puberty-matched control group.
1539 7536205 Improvement in glycemic control, as determined by a change in hemoglobin-A1c, correlated positively with improvement in IGF-I, IGF-II, IGFBP-3, GHBP, and weight gain after 1 month of insulin therapy.
1540 7698051 Glycated hemoglobin was measured to determine the clinical importance of catheter malfunctions and decreases in pump flow due to insulin aggregation in the pump chamber.
1541 7698505 Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3.
1542 7698518 In each subject, we measured glycemic control, insulin-stimulated glucose uptake in the whole body and forearm, rates of glucose and lipid oxidation, and muscle glycogen, glycogen synthase, and glucose transport protein (GLUT4) concentrations.
1543 7700245 Exposure of the cells to 0.1 microM insulin caused 60% and 80% decreases in the steady state levels of P450 2B and 2E proteins, respectively, within 24 hr.
1544 7700245 Indeed, 5-6 hr of insulin treatment produced 80 and 50% decreases in P450 2B and 2E mRNA levels, respectively.
1545 7706456 Together, these data demonstrate that GLUT4 upregulation overcomes the glucose transporter translocation defect and alleviates insulin resistance in genetically diabetic mice, thus resulting in markedly improved glycemic control.
1546 7706480 Since the conditioned culture media from the HITra2 cells exhibited an anti-IL-1 beta activity of only 0.5 U/ml, and mixed culture of HITra2 cells and isolated rat islets prevented IL-1 beta induced inhibition of insulin release, it is likely that IL-1ra acts locally at the cell surface.
1547 7706500 We report the findings of altered insulin secretion and insulin action in two brothers affected with CFTDM and glucose intolerance as well as in their nonconsanguineous glucose-tolerant parents.
1548 7706500 Despite a 45-90-fold increase in both fasting and postprandial serum insulin levels, both CFTDM patients had diabetes mellitus.
1549 7714089 In adolescents (n = 104) treated for insulin-dependent diabetes mellitus (IDDM), serum IGF-I (-19%), osteocalcin (-28%), and skeletal ALP (-28%) were markedly decreased, whereas total ALP was significantly increased (29%), and serum PICP remained normal.
1550 7882592 The insulin resistance of this disease may be mediated by tumor necrosis factor-alpha (TNF-alpha).
1551 7883122 Hexokinase II (HKII) is the predominant hexokinase isozyme expressed in insulin-responsive tissues.
1552 7883976 The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population.
1553 7883976 Since the FABP2 threonine-encoding allele was found to be associated with insulin resistance and increased fat oxidation in vivo, we further analyzed the FABP2 gene products for potential functional differences.
1554 7885272 Insulin-stimulated receptor autophosphorylation reflects an early physiologic step in transmission of the insulin signal, and for that reason, changes in autophosphorylation activity of the insulin receptor were used as a marker to determine the functionality of the insulin receptor.
1555 7885286 Although flux through gluconeogenic/glycolytic pathways involves regulation of many enzymes, we presently report the effects of insulin on expression of two key enzymes in these metabolic pathways, ie, phosphoenolpyruvate carboxykinase (PEPCK) and glucokinase (GK).
1556 7885286 Although the mean level of liver mRNA transcripts encoding PEPCK was increased to nearly 300% in diabetic animals as compared with nondiabetic controls (100%), it was significantly lower in pioglitazone-treated diabetic rats (119% of control) than in diabetic rats without pioglitazone (223% of control) after insulin treatment.
1557 7895657 Recent studies indicated a direct role for adipose expression of TNF alpha in obesity-linked insulin resistance and diabetes.
1558 7895657 Incubation of 3T3-L1 adipocytes with TNF alpha also inhibited insulin-stimulated 2-deoxyglucose uptake as well as expression of GLUT4 protein.
1559 7895862 The regulation of IRS-1 has been analyzed in animal models of insulin resistance, and its mechanism has been studied in culture cells.
1560 7895862 In cultured cell such as 3T3-L1 or 3T3-F442A adipocytes, IRS-1 was negatively regulated both by insulin and dexamethasone by different mechanisms.
1561 7895862 Insulin regulates the IRS-1 expression at protein level mainly by decreasing the half life of IRS-1 protein, and dexamethasone regulates it at mRNA level mainly by decreasing the half life of IRS-1 mRNA.
1562 7540553 Hyperglycemia is likely to be the mechanism of NOS inhibition since insulin treatment reversed this abnormality.
1563 7540574 In the beta TC3 insulin-secreting beta-cell line, glucose rapidly induces the tyrosine phosphorylation of the 97-kDa insulin receptor beta-subunit.
1564 7598712 Recent evidence suggests that expression of tumor necrosis factor-alpha (TNF-alpha) by adipocytes is a molecular mediator of insulin resistance in obesity.
1565 7607616 An H1 histamine blocker markedly diminished the skin reaction to insulin, and her plasma glucose and glycosylated hemoglobin AIc became well controlled.
1566 7608255 Evidence suggests that hyperinsulinemic insulin resistance may increase serum levels of ovarian androgens and reduce sex hormone-binding globulin (SHBG) levels in humans.
1567 7608267 To address the relationship of insulin-like growth factor-I (IGF-I) to diabetes control, we determined IGF-I levels in 137 subjects age 17 yr and younger with recently diagnosed insulin-dependent diabetes mellitus in a population-based cohort study between 3 and 11 months after diagnosis (mean 4.9 months).
1568 7608267 These results suggest that lower IGF-I levels are related to poorer metabolic control of diabetes in the period following insulin-dependent diabetes mellitus diagnosis in all young persons regardless of age or pubertal status.
1569 7608282 SHBG correlated negatively with cord insulin concentrations [males, -0.31 (P < 0.01); females, -0.35 (P < 0.001)], birth weight [males, -0.25 (P < 0.05); females, -0.36 (P < 0.001)] and other measures of neonatal size.
1570 7608643 Whilst these correlations may represent cause and effect for plasminogen activator inhibitor, there is no evidence that changes in levels of proinsulin-like molecules influence levels of other risk factors.
1571 7787143 Six weeks after the onset of insulin-treated streptozotocin diabetes (STZ) in Munich-Wistar rats, the effect of a low-sodium (LNa) and a low-salt (LNaCl) diet on renal function and on plasma and kidney tissue angiotensin II (AIIp, AIIk) was tested.
1572 7787209 In summary, insulin-like growth factor-I levels are increased in some pancreatic cancer patients but this does not seem to favor tumor spread; however IGF-I could be involved influencing glucose homeostasis.
1573 7788961 We have investigated the effects of interleukin-2 (IL-2) on the activation of suppressor T lymphocytes in autoimmune thyroid disease (AITD), with insulin-dependent diabetes mellitus (IDDM) as an autoimmune disease control; this was accomplished by measuring the expression of major histocompatibility complex class II (HLA-DR), CD25 (IL-2 alpha receptor (R)), and IL-2 beta R expression on their surfaces by flow cytometric analysis.
1574 7789625 Thus, in CP-positive IDDM, pharmacological doses of GLP-I reduce glycemic excursions after meals by a mechanism(s) not dependent on stimulation of insulin secretion, presumably involving delayed gastric emptying.
1575 7789629 GLUT4 translocation and activation of glucose uptake in skeletal muscle can be induced by both physiological (i.e., insulin, nerve stimulation, or exercise) and pharmacological (i.e., phorbol ester) means.
1576 7789629 We found that stimulation of C2C12 myotubes with both insulin (10(-7) mol/l, 5 min) and glucose (25 mmol/l, 10 min) induces a comparable increase of the GLUT4 content in the plasma membrane.
1577 7789634 Islet-1 (Isl-1) is a unique transcription factor that binds to the enhancer region of the insulin gene.
1578 7789637 In contrast, mutations in the MODY1 gene are associated with an inability to increase insulin secretion as the plasma glucose concentration increases above 7-8 mmol/l and the normal priming effect of glucose on insulin secretion is lost.
1579 7792741 In univariate analysis, PAI-1 activity correlated with serum triglycerides (rs = 0.43; p < 0.0001), insulin sensitivity (rs = -0.30; p = 0.004), and immunoreactive insulin (rs = 0.45; p < 0.0001).
1580 7792741 However, the relationship between PAI-1 activity and plasma specific insulin (IEMA) was weaker (rs = 0.24; p = 0.019) than those with intact proinsulin (rs = 0.53; p < 0.0001) and des-31,32-proinsulin (rs = 0.54; p < 0.0001) despite the low concentrations of these proinsulin-like molecules.
1581 7792741 In multiple regression analysis, only des-31,32-proinsulin (p = 0.001) and serum triglycerides (p = 0.013) were significant determinants of PAI-1 activity.
1582 7796922 Both galanin and somatostatin inhibit insulin release from pancreatic beta-cells by opening KATP through the activation of G-protein.
1583 7796936 The recent finding that GLUT 4 is also expressed in the hypothalamus suggests that this brain region, which is outside the blood-brain barrier and therefore sensitive to circulating insulin, may experience stimulation of glucose uptake in response to insulin.
1584 7543091 To investigate the Ca2+ signaling pathways by which GLP-1 may stimulate the secretion of insulin from pancreatic beta-cells, we examined its effects on the concentration of free intracellular Ca2+ ([Ca2+]i) while simultaneously determining what action it exerts on ion channel function.
1585 7543098 Shc phosphorylation in cells following growth factor, insulin, cytokine, and lymphocyte receptor activation leads to its association with Grb2 and activation of Ras.
1586 7543110 Immunoblot analysis demonstrated that intact IGFBP-3 doublet was diminished to 41 +/- 7% of controls, whereas the major IGFBP-3 fragment (30 kDa) was increased in IDDM sera before insulin therapy.
1587 7543110 These results suggest an important role of insulin in the regulation of IGFBP-3 protease activity.
1588 7543110 Increased IGFBP-3 proteolysis in the sera of children with IDDM may serve to counteract the catabolic state induced by insulin deficiency.
1589 7615080 The effects of insulin and IGF-I on the cell surface quantities of GLUT1, GLUT3 and GLUT4 glucose transporters in L6 myotubes were determined with the exofacial bis-mannose phololabel (ATB-BMPA).
1590 7622000 Specific high-affinity insulin and insulin-like growth factor I (IGF-I) binding, glucose transporter proteins GLUT1 and GLUT4, glycogen synthase and pyruvate dehydrogenase proteins, and their specific mRNAs were identified in fused myotubes.
1591 7622001 To examine the kinetic steps in insulin's in vivo action, we have assessed the temporal relationship between arterial insulin, interstitial insulin, glucose disposal rate (GDR), and insulin receptor kinase (IRK) activity in muscle and between portal insulin, hepatic glucose production (HGP), and IRK activity in liver.
1592 7626603 Moreover, elimination of the phosphorylation sites of pp120/HA4 impaired the ability of insulin to stimulate the ecto-ATPase activity.
1593 7628352 Nitric oxide (NO) may be a mediator of beta-cell damage in insulin-dependent diabetes mellitus. beta-Cells express the inducible form of NO synthase (iNOS) and produce large amounts of NO upon exposure to cytokines. iNOS requires the amino acid arginine for NO formation.
1594 7628391 We investigated the role of islet pyruvate dehydrogenase (PDH) enzyme activity and fatty acid oxidation in the impaired insulin secretion in spontaneously diabetic GK rats.
1595 7544790 To explore whether PTP1B, a widely expressed, non-receptor-type PTPase, regulates insulin signaling, we used osmotic shock to load rat KRC-7 hepatoma cells with affinity-purified neutralizing antibodies that immunoprecipitate and inactivate the enzymatic activity of recombinant rat PTP1B in vitro.
1596 7544790 In order to characterize the potential site(s) of action of PTP1B in insulin signaling, we also determined that insulin-stimulated receptor autophosphorylation and insulin receptor substrate 1 tyrosine phosphorylation were increased 2.2- and 2.0-fold, respectively, and that insulin-stimulated receptor kinase activity toward an exogenous peptide substrate was increased by 57% in the PTP1B antibody-loaded cells.
1597 7646509 Direct incubation of cardiac nuclei with insulin resulted in a comparably significant increase of Glut4 transcription.
1598 7646509 These findings suggest that expression of the cardiac Glut4 gene is subject to regulation by insulin at the transcriptional level, a process possibly involving nuclear association of the hormone.
1599 7648516 The decrease in myocardial lipoprotein lipase (LPL) activity observed previously in acute, severe models of insulin-deficient diabetes may be a compensatory response to hypertriglyceridemia and a sustained increase in fatty acid delivery to cardiomyocytes.
1600 7651354 Specifically, the addition of insulin or hydrocortisone to culture media or the lowering of the initial plating cell density increased cell GSH by increasing the activity of GCS.
1601 7657033 The increase in insulin responsiveness was accompanied by a 2.5-fold increase in the total tissue content of the glucose transporter GLUT4.
1602 7663508 We now demonstrate a defect in proinsulin processing associated with the virtual absence of CPE activity in extracts of fat/fat pancreatic islets and pituitaries.
1603 7487987 Here, using isolated rat pancreatic islets, we show that high-concentration nicotinamide (20 mM), but not low-concentration nicotinamide (5 mM), attenuates the interleukin-1 beta-evoked inhibition of glucose-induced insulin secretion by preventing the induction of interferon regulatory factor-1, a transcriptional factor which plays an essential role in inducible nitric oxide synthase gene expression, and the interleukin-1 beta-induced nitric oxide formation.
1604 7545695 To investigate whether previously reported increased levels of insulin-like growth factor-binding protein-1 (IGFBP-1) in GH-deficient patients only reflect decreased levels of insulin or are elevated in relation to insulin, diurnal profiles of IGFBP-1 and insulin were determined in plasma from patients with GH levels below 0.2 microgram/L throughout 24 h (n = 23) and compared to profiles from patients with insulin-dependent diabetes mellitus (IDDM; n = 9) and healthy subjects (n = 12).
1605 7554320 The presence of congenital combined growth hormone and gonadotrophin deficiency on the basis of a suprapituitary defect suggests the existence of common or related pathways regulating GnRH and GHRH synthesis or secretion and may have contributed to the ultimate development of insulin resistance and hyperlipidaemia.
1606 7555530 In hypertensive NIDDM patients, the activity of the renin-angiotensin-aldosterone system, the level of serum insulin, glycemic control, renal function, and proteinuria may be important determinants of the blood pressure response to ACE inhibition.
1607 7556621 Insulin treatment (4 days) only marginally increased ob mRNA, but restored euglycemia and overcorrected FAS, GLUT4 and PEPCK expression.
1608 7556873 Insulin secretion from intact islets in response to glucose, glyceraldehyde, succinate monomethylester and tetramethyl p-phenylenediamine, which reduces cytochrome c directly, was significantly impaired in GK rats compared to control rats (P < 0.05, P < 0.01, P < 0.05 and P < 0.05, respectively).
1609 7556948 We have also observed that the development of renal hypertrophy in the insulin-dependent diabetic BB rat and NOD mouse is associated with increased expression of TGF-beta 1 in the kidney and that short-term administration of antibodies capable of neutralizing the activity of TGF-beta in the streptozotocin mouse model of diabetes results in attenuation of whole kidney and glomerular hypertrophy and overexpression of mRNAs encoding matrix components.
1610 7556949 The mitogen-activated protein (MAP) kinases and ribosomal S6 protein kinases in the skeletal muscle of insulin-resistant long-term (2 and 6 months' duration) diabetic rats were investigated to understand further the changes in insulin intracellular signaling pathways that accompany diabetes.
1611 7556949 Intravenous injection of insulin moderately activated both the 42-kDa MAP kinase (p42mapk) and a 44-kDa MAP kinase (p44erk1) in the 2-month control rats but not in the 2-month diabetic rats.
1612 7560085 The coding sequences and splicing donor and acceptor sequences of the Tnfa gene, a candidate gene for Idd-16, were identical in the NOD, CTS, and BALB/c alleles, ruling out amino acid changes in the TNF molecule as a determinant of insulin-dependent diabetes mellitus susceptibility.
1613 7562114 It is suggested that the PUFA-mediated suppression of insulin-dependent gene expression of lipogenic enzymes can be ascribed to a decrease in insulin receptor binding primarily and also to receptor phosphorylation.
1614 7575448 In these animals insulin failed to recruit GLUT4 from the microsomal fraction, whereas the hormone induced a significant decrease (41 +/- 4%) of microsomal GLUT4 in lean controls.
1615 7575448 In addition to the translocation of GLUT4, insulin was found to promote the movement of the small GTP-binding protein rab4A from the cytosol (decrease to 61 +/- 13% of control) to the plasma membrane (increase to 177 +/- 19% of control) in lean rats with no effect of the hormone on rab4A redistribution in the obese group.
1616 7587842 Findings in epidemiology and animal experimentation suggest that autoimmunity in insulin-dependent diabetes mellitus (IDDM) may be triggered by dietary cow-milk protein, particularly bovine serum albumin (BSA).
1617 7587855 After the observation that a 2-h infusion of AC137 at a rate of 150 micrograms/h, in conjunction with the subjects' usual morning insulin dose, decreased postprandial hyperglycemia in 6 subjects with IDDM, a double-blind placebo-controlled two-period crossover design in an additional 18 IDDM patients was undertaken to confirm and extend the observation.
1618 7589426 Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells.
1619 7673396 Combined positivity for the 5' INS 1/1 genotype and for one of three other HLA-DQ genotypes associated with an intermediate risk for IDDM conferred an age-independent RR of 12.1 (P < 10(-4)).
1620 7485492 Phosphorylated IRS-1 then interacts with the p85 alpha subunit of phosphatidylinositol 3-kinase (PI3K), Nck, growth factor receptor-bound protein 2 (GRB2), and Syp, thus branching insulin's signal for both mitogenic and metabolic responses.
1621 7486683 In HIR 3.5 cells, which contain similar numbers of PDGF and insulin receptors, insulin, but not PDGF, stimulated tyrosyl phosphorylation of IRS-1.
1622 7486683 Moreover, PDGF, but not insulin, caused tyrosine phosphorylation of phospholipase C gamma in HIR 3.5 cells.
1623 7486683 Thus, the insulin signal differs from that of PDGF by the insertion of a cytosolic, nonreceptor SH2 domain docking protein (IRS-1).
1624 7486814 Upon stimulation with thrombin, the mean peak [Ca2+]i for the insulin-treated (309 +/- 97 nmol/L) and untreated (339 +/- 135 nmol/L) diabetic rats was significantly higher than the concentration for the normal rats (213 +/- 101 nmol/L).
1625 7472513 Islet amyloid polypeptide (IAPP) or amylin is a hormone candidate predominantly expressed in insulin cells.
1626 7476323 This study was designed to examine the effects of insulin deficiency on the regulation of HSL in isolated adipocytes.
1627 7476323 Compared with levels in control rats, 10 days of insulin deficiency increased HSL activity twofold (P < .05), as assayed for neutral cholesterol esterase activity, and insulin treatment returned HSL activity to normal.
1628 7476323 In conclusion, our studies suggest that 10 days of insulin deficiency increases HSL expression via pretranslational mechanisms and short-term insulin treatment returns HSL activity to normal via posttranslational mechanisms in adipose tissue.
1629 7476331 Mitomycin C treatment of MNC from IDDM patients abolished insulin secretion inhibition in recipient mice.
1630 7476331 Cells from chronically IDDM patients cultured with concanavalin A (Con A) increased insulin secretion inhibition; despite this, cells from children during the remission period cultured with Con A failed to modify insulin secretion in recipients.
1631 7476335 Intestinal activities of the redox enzymes, GSH peroxidase, GSSG reductase, and glucose-6-phosphate dehydrogenase (G6PD), were significantly decreased by 17 hours' insulin treatment, whereas only G6PD was decreased by fasting.
1632 7476335 Insulin treatment for 7 consecutive days increased hepatic G6PD activity by fourfold but was without effect on intestinal G6PD, suggesting tissue specificity in insulin regulation of G6PD.
1633 7479313 NPY synthesis in the ARC is thought to be regulated by several factors, notably insulin, which may exert an inhibitory action.
1634 7479313 The effects of NPY injected into the PVN and other sites include hyperphagia, reduced energy expenditure and enhanced weight gain, insulin secretion, and stimulation of corticotropin and corticosterone release.
1635 7485207 To determine whether angiotensin-converting enzyme (ACE) inhibition with captopril reduces the progression of microalbuminuria to overt proteinuria in normotensive patients with insulin-dependent diabetes mellitus (IDDM).
1636 7499194 In contrast, both the Shc and IRS-1 PTB domains bind psi psi psi XXN beta 1 beta 2pY sequences derived from insulin and interleukin 4 receptors, although specificities vary in detail.
1637 7489848 The (MHC) class II association with insulin-dependent diabetes mellitus (IDDM) is well documented.
1638 8527305 Insulin-stimulated translocation of GLUT4 in isolated rat adipocytes was markedly inhibited by wortmannin.
1639 8719940 The study aimed to assess vascular reactivity to noradrenaline with and without neuropeptide Y in diabetic rats, and to determine whether any abnormality could be attributed to insulin deficiency or to hyperglycaemia per se.
1640 8750222 Insulin-mediated activation of GS depends upon protein phosphatase-1 (PP1), which dephosphorylates the relevant sites of GS.
1641 8750222 In order to determine whether defects in PP1 activation cause subnormal activation of GS or whether PP1 activation itself is normal, we administered a short insulin infusion to 8 NIDDM subjects and 8 healthy controls matched for gender, age, and body mass index (BMI).
1642 8750222 PP1 activity had returned towards basal levels after insulin infusion; NIDDM group 156 +/- 24.7 to 184.1 +/- 28.1 U mg-1; control group 220.8 +/- 30.1 to 233.8 +/- 29.8 U mg-1.
1643 8750222 In the NIDDM group there was a positive correlation between the increases in GS fractional activity and PP1 activity following insulin stimulation r = 0.77; p < 0.025).
1644 8750222 These data indicate that in vivo insulin-dependent activation of muscle PP1 is transient in normal subjects but is delayed in NIDDM.
1645 8770334 There are conflicting reports about the effects of ACE inhibitors (ACEI) on insulin sensitivity and glycaemic control.
1646 8781713 Since glutamic acid decarboxylase-65 (GAD-65) is a target autoantigen in IDDM, we investigated whether the cytokines IL-1 beta, TNF alpha IFN gamma altered islet cell expression of GAD-65 and whether the effect of cytokines on GAD-65 expression was similar to their effect on insulin secretion.
1647 8781713 We found that: 1) IL-1 beta at low dose (1 U/ml) which stimulated insulin secretion, had no effect on GAD-65 expression, whereas higher doses of IL-1 beta (10, 100, 1000 U/ml) which inhibited insulin secretion, decreased GAD-65 expression. 2) TNF alpha at doses of 10, 100, 1000 U/ml which stimulated insulin secretion had no effect on GAD-65 expression. 3) IFN gamma at doses of 10, 100, 1000 U/ml had no effect on insulin secretion or on GAD-65 expression. 4) In combination, IL-1 beta plus TNF alpha and IFN gamma showed a similar inhibitory effect on GAD-65 expression as IL-1 beta alone.
1648 8808235 The purpose of this study was to examine the effect of prepregnancy treatment of insulin-dependent diabetes mellitus (IDDM) nephrotic women with captopril angiotensin converting enzyme inhibitor (ACE-1), on maternal renal function throughout pregnancy and on the fetomaternal outcome.
1649 8817689 IGFBP-1 secretion in humans is regulated by insulin and the counter-regulatory hormones with a high production rate and rapid turnover.
1650 8834772 In this study we show that administration of vanadate or selenate to streptozotocin-induced diabetic rats not only normalizes blood glucose levels similarly to insulin but also positively affects the expression of two key metabolic enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS).
1651 8839251 Glucagon-like peptide-1 (GLP-1) is the major incretin hormone from the distal small intestine which stimulates basal and glucose-induced insulin secretion.
1652 8839251 During a 1 hour incubation, GLP-1 [1 nM] stimulated insulin secretion 2-fold (p < 0.01 vs controls).
1653 8839251 Incubating RINm5F for 24 h with GLP-1 [1 nM], a 1.6-fold higher cellular insulin content was observed (p < 0.01 vs controls).
1654 8839264 Interestingly, B-cells in the allografts with a dense insulin immunoreactivity exhibited GLUT2 glucose transporter expression in both localizations, whereas B-cells with a faint insulin immunoreactivity exhibited GLUT2 glucose transporter only in the plasma membrane.
1655 8927025 In addition, unlike vanadyl sulfate, insulin was unable to improve the stimulation exerted by glucagon and isoproterenol on adenylyl cyclase activity in STZD rats.
1656 8927025 These results suggest that vanadyl sulfate mimics the effects of insulin to restore the defective levels of G-proteins and adenylyl cyclase activity.
1657 8927031 STZ-induced diabetes (an animal model for insulin-dependent diabetes mellitus, IDDM) resulted in a 2-fold increase in rat liver NMT activity as compared with control animals.
1658 8927032 Aldose reductase inhibitors and vanadate addition reversed the sorbitol accumulation, whereas insulin could not reverse it.
1659 8960251 The activity of GST and cytosol Se-GSHPx, as well as GSH content, returned to a normal values after insulin treatment, while the activity of non Se-GSHPx was reduced of about 50% in relation to the control values.
1660 8522056 We demonstrate that restricted overexpression of GLUT4 in fast-twitch skeletal muscles of myosin light chain (MLC)-GLUT4 transgenic mice induces a 2.5-fold increase in insulin-stimulated 2-deoxyglucose uptake in transgene-overexpressing cells.
1661 8522066 In summary, IGF-I significantly lowered blood glucose as reflected by short-term and long-term indexes of glycemic control and increased insulin sensitivity.
1662 8621530 Glutathione S-transferase fusion proteins containing the Grb10 SH2 domain associated in an insulin-dependent manner with insulin receptors from cell lysates and with purified insulin receptors.
1663 8663067 This reduction in HK II mRNA was prevented in skeletal muscle, where overexpression of GLUT4 caused a 2.5-fold increase in basal and insulin-stimulated glucose uptake.
1664 8663361 Both insulin alone and okadaic acid alone stimulated the translocation of glucose transporter 4 to the plasma membrane.
1665 8666133 Cholinergic agonists amplify insulin release by several pathways, including activation of phospholipase C, which hydrolyzes membrane polyphosphoinositides.
1666 8666136 We determined the effect of a physiological insulin concentration (300 pmol/l) on the Ca2+ response of vascular smooth muscle cells of the porcine right coronary artery to endothelin 1 (ET-1); furthermore, we examined the cellular Ca2+ stores affected by insulin (i.e., Ca2+ stores releasable by inositol 1,4,5-trisphosphate, caffeine, and ionomycin).
1667 8666136 Acute insulin exposure (20 min) significantly attenuated the Ca2+ response of single smooth muscle cells to 10 nmol/l ET-1.
1668 8666137 Inhibition of tumor necrosis factor (TNF)-alpha action has recently been shown to reverse insulin resistance dramatically and to improve glycemic control in obese rodents.
1669 8666137 TNF-alpha neutralization over a period of 4 weeks had no effect on insulin sensitivity in obese NIDDM subjects.
1670 8666140 Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3 (PC3).
1671 8666140 Expressions of insulin and PC3, but not PC2, are coordinately regulated by glucose, consistent with the important role of PC3 in regulating proinsulin processing.
1672 8666149 Insulin-induced hypoglycemia (plasma glucose = 1.9 +/- 0.1 mmol/l) activated parasympathetic nerves to the pancreas as assessed by increased plasma pancreatic polypeptide (PP) levels (delta = 135.0 +/- 36.8 pmol/l, P < 0.01), produced sympathoadrenal activation as assessed by elevations of plasma epinephrine (EPI) (delta = 22.3 +/- 2.95 nmol/l, P < 0.0005) and norepinephrine (NE) (delta = 3.72 +/- 0.77 mmol/l, P < 0.0025) and increased plasma immunoreactive glucagon (IRG) (delta = 920 +/- 294 ng/l, P < 0.025).
1673 8666154 However, plasma insulin itself does not acutely regulate leptin production.
1674 8674895 Insulin at a concentration in the physiological range (10(-10)-10(-7) mol/l) potently suppressed CNP secretion, whereas insulin at the same concentration did not suppress endothelin (ET) secretion from EC.
1675 8675570 The SHBG levels correlated significantly with the insulin concentrations (r = -0.643, P < 0.05) and with the GIR (r = 0.615, P < 0.05) before the treatment.
1676 8675570 The SHBG levels (P < 0.02) and GIR (P < 0.01) increased, and the insulin concentrations (P < 0.01) decreased significantly during the treatment.
1677 8675570 Briefly, these results suggest that insulin may directly affect the SHBG levels and that SHBG may constitute an index of the insulin resistance only in the hyperinsulinemic state.
1678 8675578 To delineate the associations between HLA-DRB1, DQB1, and APS-II, we analyzed APS-II patients with or without beta-cell autoimmunity [i.e. insulin-dependent diabetes (IDD) and/or islet cell or glutamic acid decarboxylase autoantibodies].
1679 8690802 Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56 +/- 13%), Rad (+96 +/- 25%), the p85alpha subunit of phosphatidylinositol-3-kinase (+92 +/- 18%) and a decrease in the lipoprotein lipase mRNA level (-49 +/- 5%), while the abundance of the other mRNAs was unaffected.
1680 8692017 In the present study, we examined if proinsulin and insulin affect the constitutive (fasting) secretion of plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) in young healthy women (N = 17).
1681 8692017 We also measured the antigen concentrations of PAI-1 and t-PA during slow and fast changes in proinsulin and insulin levels induced by oral (OGTT) and intravenous (IVGTT) glucose tolerance tests.
1682 8692017 Our findings suggest that proinsulin and insulin have no influence on the regulation of plasma levels of PAI-1 and t-PA in young healthy women, irrespective of intake of contraceptive steroids.
1683 8692017 They aimed to examine the effect of proinsulin and insulin on fasting secretion of plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA).
1684 8692017 The clinical researchers also studied the antigen concentrations of PAI-1 and t-PA during slow and fast changes in proinsulin and insulin levels induced by oral and intravenous glucose tolerance tests.
1685 8692017 After 6 months of OC treatment, t-PA levels fell only during the oral glucose tolerance test (p 0.05) even though proinsulin and insulin responded similarly to the glucose loads.
1686 8692017 These findings suggest that neither proinsulin nor insulin regulate plasma levels of PAI-1 and t-PA in young healthy women regardless of OC use status.
1687 8692940 Liver glucokinase catalyzes the first committed step in the disposal of glucose, and beta-cell glucokinase catalyzes a rate-limiting step required for glucose-regulated insulin release.
1688 8779938 We have investigated the roles of eukaryotic initiation factor 4E (eIF-4E), the cap-binding protein, and the translational regulator, PHAS-I, in the effects of insulin and alloxan-induced diabetes on protein synthesis in rat skeletal muscle.
1689 8779938 The effects of both insulin and diabetes on PHAS-I binding to eIF-4E appeared to be due to changes in PHAS-I phosphorylation.
1690 8779938 Neither insulin nor diabetes changed the phosphorylation state of eIF-4E.
1691 8779938 The results indicate that the effects of both insulin and diabetes on protein synthesis in skeletal muscle involve modulation of the interaction of PHAS-I and eIF-4E.
1692 8780216 Because of the significant role of insulin in maintaining BAT thermogenesis, we employed a transgenic mouse model of diabetes to investigate the regulation and function of HSPs in BAT thermogenesis.
1693 8781295 Therefore, we examined the effect of TNF-alpha on basal and insulin-mediated transport of 2-deoxy[3H]-glucose in L6 rat muscle cells.
1694 8781295 Comparative experiments with 3T3-L1 adipocytes showed that in cells cultured with insulin, TNF-alpha decreased basal transport but the insulin-stimulated increase was unaffected.
1695 8781557 The effects of exogenous prostaglandins, inflammatory mediators known to be increased in pancreatic beta-cells by IL-1 beta, on the replication and long-term insulin secretion by beta-cells were investigated.
1696 8782826 We infer the existence of a gene NIDDM2 causing NIDDM associated with low insulin secretion, and suggest that NIDDM2 and MODY3 may represent different alleles of the same gene.
1697 8784069 The cytokine combination of interleukin-1 beta (50 U/mL), tumor necrosis factor-alpha (10(3) U/mL), and interferon-gamma (10(3) U/mL) induced significant increases in MDA and nitrite and significant decreases in insulin and DNA in islets after 60-h incubation.
1698 8784108 Serum leptin correlated positively with serum insulin (r = 0.51, p < 0.001) and with plasma glucose (r = 0.61, p < 0.001).
1699 8784789 In freshly isolated adipocytes, insulin induced a rapid translocation of GLUT4 to the plasma membrane fraction, which was followed by a slower transition of the transporter into a detergent resistant caveolae-rich region of the plasma membrane.
1700 8784789 Treatment with isoproterenol plus adenosine deaminase rapidly inhibited insulin-stimulated glucose transport by 40%, and at the same time GLUT4 disappeared from the caveolae-rich fraction and from plasma membranes as a whole.
1701 8784789 Insulin stimulates glucose uptake in adipocytes by rapidly translocating GLUT4 from intracellular stores to the plasma membrane.
1702 8792100 These results suggest that an increase of Na-Li CT may not be due to the stimulatory effect of endogenous or exogenous insulin, and reflect a genetic predisposition for hypertension, and hence diabetic nephropathy, not only in IDDM but also NIDDM patients.
1703 8796133 Insulin-dependent diabetes mellitus is not associated with any significant changes in IGF-II levels during puberty.
1704 8796133 The binding of IGFBP-3 for both IGF-I and IGF-II is unaltered by insulin-dependent diabetes mellitus.
1705 8798677 Overexpression of the insulin receptor in 32DIR cells increased IRS-1 tyrosine phosphorylation and mediated insulin-stimulated DNA synthesis.
1706 8805677 These data suggest that the cytoplasmic region, in particular the tyrosine phosphatase-like domain, is the major target of IA-2 Abs in insulin-dependent diabetes, and that autoantibody reactivity is specific for IA-2 or IA-2-like molecules.
1707 8884164 In refractory hypoglycaemia due to hyperinsulinaemia such as during sulphonylurea overdosage or quinine treatment, the long-acting somatostatin, octreotide, may suppress insulin release and restore euglycaemia.
1708 8884847 We have investigated whether a possible dysregulation of the storage and function of islet amyloid polypeptide (IAPP) in the endocrine pancreas of 4-month-old spontaneously diabetic Goto-Kakizaki (GK) rats might contribute to the impairment of glucose-induced insulin secretion previously reported in these rats.
1709 8910278 These results indicate that aP2 is central to the pathway that links obesity to insulin resistance, possibly by linking fatty acid metabolism to expression of TNF-alpha.
1710 8910437 However, Grb2 association with IRS-1 could not be detected in the basal or insulin-stimulated states, and mitogen-activated protein kinase (MAPK) activity could not be stimulated by insulin, epidermal growth factor, or platelet-derived growth factor.
1711 8910437 In addition, Grb2 association with Shc and activation of MAPK and the p70 S6 kinase were insensitive to insulin stimulation.
1712 8910817 Increased IGFBP-3 protease activity has been shown in sera of children with IDDM as well as a decrease in this activity in response to insulin therapy.
1713 8911856 Furthermore, we studied siblings positive for islet cell antibodies (ICAs) and/or insulin autoantibodies (IAAs) to evaluate the impact of the-23 HphI INS +/+ genotype on their beta-cell function assessed by sequential intravenous glucose tolerance tests and on their progression to IDDM.
1714 8911856 These observations suggest that the-23 HphI INS +/+ polymorphism is associated with an increased risk of IDDM in subjects without predisposing genes in the MHC region.
1715 8911988 Freshly isolated rat cardiomyocytes, primary cultured cardiomyocytes and the cardiac cell line H9c2 were used to elucidate acute and chronic effects of the sulfonylurea glimepiride on basal and insulin-stimulated glucose uptake and on the expression of the transporter isoforms GLUT1 and GLUT4.
1716 8911991 Sulfonylureas, in contrast to insulin, seem able to inhibit the fibrinolytic system, possibly via the stimulating effect of proinsulin on the endothelial PAI-1 expression.
1717 8913531 It was found that neither of these TGF-alpha concentrations affected beta-cell mitogenesis, insulin content or insulin secretion.
1718 8913531 TGF-beta (500 pM) stimulated insulin secretion but did not influence islet insulin content or beta-cell mitogenesis either alone or in combination with TGF-alpha (200 pM or 20 nM).
1719 8914428 Several mechanisms mediated by hyperinsulinemia can be entertained as follows: 1) sodium and water retention, 2) increased sympathetic nerve activity and reduced catecholamine clearance, 3) increased intracellular calcium concentration and reduced magnesium concentration, 4) increased coagulant activity and impaired fibrinolytic activity, 5) impaired endothelium-dependent NO synthesis and release, 6) increased vascular responsiveness for the vasoactive substrates, 7) increased proliferation of vascular smooth muscle cell by activation of protein kinase C or mediated by insulin and IGF-1 action.
1720 8914990 Insulin treatment of diabetic rats increased GLUT1 level at the BBM but was without effect on expression of the protein at the BLM.
1721 8916919 In many tissues, the insulin receptor-related receptor (IRR) is colocalized with the homologous receptors for insulin and insulin-like growth factor-I (IGF-I).
1722 8916919 Since a ligand for the IRR has not yet been identified, it has been proposed previously that IRR may be activated and transduce its signal via formation of hybrids with the insulin and IGF-I receptors.
1723 8916919 While insulin was capable of stimulating insulin receptors autophosphorylation in these cells, there was no detectable increase in the total phosphotyrosine content of IRR.
1724 8921700 Alpha-glucosidase inhibitor can suppress postprandial hyperglycemia by delaying the absorption of carbohydrates in the intestine, and may be useful in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) and preserved insulin secretion.
1725 8922354 Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin.
1726 8922354 Because the insulinotropic effect of GIP is reduced in NIDDM, it should be clarified whether defects in the GIP receptor gene contribute to the impaired insulin secretion in NIDDM.
1727 8922356 Based on our observations, we propose a two-step model for insulin processing in which insulin is first processed by an enzyme(s) into an intermediate peptide that binds to class II and then class II functions as a template to guide the processing of this partially processed peptide by cathepsin D into a T-cell epitope.
1728 8922366 Interleukin-1beta (IL-1beta) has been shown to inhibit glucose-induced insulin secretion from rat islets and purified beta-cells, primarily through the generation of nitric oxide (NO).
1729 8922366 IL-1beta also diminished insulin secretion induced by pure mitochondrial fuels, 40 mmol/l K+, or a phorbol ester.
1730 8922366 In contrast, in INS-1 cells, IL-1beta (10 or 100 pmol/l) reduced both basal and glucose-induced insulin secretion by 50%, but insulin content was also reduced by 35%.
1731 8922366 Thus, in rat islets, IL-1beta (via the generation of NO) abolishes insulin exocytosis in association with large decreases in the ATP/ADP (and GTP/GDP) ratio, implying the impairment of mitochondrial function.
1732 8922366 In contrast, in INS-1 cells, IL-1beta appears to impair cytosolic synthesis of purine nucleotides and insulin biosynthesis selectively (both possibly reflecting decreased glycolysis) with little direct effect on insulin exocytosis itself.
1733 8922368 Its stimulatory effect on glucose uptake was associated with an intracellular redistribution of GLUT1 and GLUT4 glucose transporters, similar to that caused by insulin, with minimal effects on GLUT3 transporters.
1734 8922372 Among the two important transcription factors for insulin gene expression, IEF1 is present both in alpha- and beta-cells, but PDX-1/IPF1/STF-1/IDX-1, a homeodomain-containing transcription factor, is present in beta-cells but not in alpha-cells.
1735 8922372 The exogenous expression of PDX-1 in alphaTC1.6 cells alone could induce islet amyloid polypeptide (IAPP) mRNA expression in the cells but not the expression of insulin, glucokinase, or GLUT2 gene.
1736 8922372 However, when betacellulin was added to the medium, the PDX-1-expressing alphaTC1.6 cells, but not the control alphaTC1.6 cells, came to express insulin and glucokinase mRNAs.
1737 8922372 These observations demonstrate the potency of PDX-1 for the expression of the insulin, glucokinase, and IAPP genes and suggest that certain regulatory factors, which can partially be modified by betacellulin, also contribute to the beta-cell specificity of gene expression.
1738 8922537 We examined insulin-mediated PKC beta I, beta II, and epsilon translocation from cytosol to cytoskeleton, and expression of PKC alpha, beta I, beta II, gamma, and epsilon isoforms using the reverse transcription polymerase chain reaction (RT-PCR) method during treatment with insulin for 240 min in rat adipocytes.
1739 8922537 However, PKC beta I mRNA was decreased for up to 60 min and then maintained at under the basal level during stimulation with insulin and TPA.
1740 8923458 MDA-MB231 human breast cancer cells are unresponsive to insulin and contain a glycoprotein inhibitor of insulin-stimulated insulin receptor (IR) tyrosine kinase activity.
1741 8923458 Prior studies in both fibroblasts from insulin- resistant non-insulin-dependent diabetes mellitus patients and transfected cells indicate that overexpression of membrane glycoprotein PC-1 reduces IR tyrosine kinase activity.
1742 8930185 We tested whether aminoguanidine (AG), a competitive inhibitor of inducible nitric oxide synthase, might block beta cell destruction and prevent insulin-dependent diabetes mellitus in vivo.
1743 8930308 In the present study we tested the hypothesis that a chronic depletion of insulin would result in opposite changes of NET and DAT mRNA expression, from those observed with chronic elevation of insulin.
1744 8931651 In patients with insulin-dependent diabetes mellitus (IDDM), the degree of glycemic control is known to alter ACTH and GH responses to hypoglycemia.
1745 8932991 The hepatic response to insulin-induced hypoglycaemia in rats involved a significant loss in glycogen and suppression of phosphoenolpyruvate carboxykinase (PEPCK) activity.
1746 8933008 The EURODIAB IDDM Complications Study involved the examination of 3250 randomly selected insulin-dependent diabetic patients, from 31 centres in 16 European countries.
1747 8971075 Glucagon (via the second messenger cAMP), retinoic acid, and glucocorticoids stimulate transcription of the PEPCK gene, whereas insulin and phorbol esters have a dominant inhibitory effect.
1748 8971075 The reactivating kinase (RK, also known as p38 mitogen activated protein kinase) is induced by insulin, hydrogen peroxide, or sodium meta-arsenite in hepatoma cells, and these effects are blocked by SB203580, a selective inhibitor of RK.
1749 8971075 Thus, although RK has a role in the regulation of lymphokine gene expression in monocytes, it is not required for the regulation of PEPCK expression by either insulin or oxidative and chemical stress in hepatoma cells.
1750 8971078 To address the role of proinsulin in the development of IDDM, we generated NOD mice transgenic for the mouse proinsulin II gene driven off a major histocompatibility complex (MHC) class II promoter to direct expression of the transgene to MHC class II bearing cells, including those in the thymus, with the aim of deleting proinsulin-reactive T-cells.
1751 8971086 Insulin (10(-6,-8,-9) mol/l) significantly stimulated ET-1 secretion by cultured cells (P < 0.05 starting from 2-h incubation).
1752 9015655 Insulin clearance was significantly increased by exercise both in healthy men (9% P < 0.05) and in IDDM subjects (15%, P < 0.05).
1753 9015655 After exercise, endogenous insulin secretion in healthy men is reduced and insulin clearance is enhanced both in healthy men and in IDDM patients.
1754 9015760 Tumor necrosis factor-alpha (TNF-alpha) can modulate the signalling capacity of tyrosine kinase receptors; in particular, TNF-alpha has been shown to mediate the insulin resistance associated with animal models of obesity and noninsulin-dependent diabetes mellitus.
1755 9015760 TNF-alpha caused a dose-dependent decrease in insulin-stimulated IRS-1 phosphorylation and EGF-stimulated receptor autophosphorylation to 47-50% of control.
1756 9059862 However, the supermitogenic insulin analogue [AspB10]insulin competed significantly more efficiently for IGF-I binding (IC50: 44 nM).
1757 9059862 [Asp(B10)]Insulin produced a stimulation of DNA synthesis (about 3-fold) which was comparable to the effect of IGF-I and significantly (P < 0.005) higher than the effect of HOE 901 with the latter being essentially equipotent to native insulin.
1758 9059862 It is suggested that differential interaction with IGF-I receptors significantly contributes to the action profile of insulin analogues.
1759 9062339 Hormone-activated insulin receptors in R-IR cells coprecipitated with three species, all recognized as Grb10 isoforms by specific Grb10 antibody.
1760 9062339 In conclusion, Grb10 interacts preferentially with insulin vs.
1761 9095091 Chronic insulin exposure increased by 70% to 90% the [Ca2+]i response to both angiotensin II and bradykinin in control subjects and normotensive non-insulin-dependent diabetic patients but not in hypertensive patients.
1762 9174153 Insulin-dependent diabetes mellitus (IDDM) and Graves' disease (GD) are autoimmune endocrinopathies and associated with distinct HLA-DR and -DQ alleles as well as several tumor necrosis factor alpha (TNF-alpha) and beta (TNF-beta) alleles.
1763 9175775 Rapamycin, a selective inhibitor of p70S6K, and the casein kinase II inhibitor DRB blocked insulin-stimulated nuclear and cytosolic p70S6K.
1764 9176170 By contrast, the ability of 1.0 mM carbachol or 300 nM cholecystokinin to stimulate insulin secretion and InsP generation was still observed.
1765 9204876 During insulin stimulation, p85 associated with pp60(IRS3) more rapidly than with IRS-1 or IRS-2.
1766 9237797 When those cells were cultured and restimulated in vitro with the B-chain of insulin, we also observed a decrease in IFN-gamma expression and an increase in IL-4, TGF-beta and IL-10 expression.
1767 9367667 Catalase (CAT) activity was not significantly affected in any of the tissues in diabetic and insulin-treated animals, however, CAT activity markedly increased in tissues with C. decidua treatment.
1768 9368055 Co-immunoprecipitation experiments performed on cell lysates derived from freshly isolated rat adipose cells incubated in the presence or absence of insulin indicated that twice as much phosphatidylinositol 3-kinase was associated with endogenous IRS-1 as with IRS-2 after insulin stimulation.
1769 9368055 To examine the role of IRS-2 in insulin-stimulated translocation of GLUT4, we studied the effects of overexpression of IRS-1 and -2 on translocation of a co-transfected epitope-tagged GLUT4 (GLUT4-HA).
1770 9368278 This increased insulin action is associated with an increase in the insulin-regulatable glucose transporters, GLUT4, and enzymes responsible for the phosphorylation, storage and oxidation of glucose.
1771 9369450 The insulin-like growth factor (IGF) binding proteins (IGFBPs) are a family of proteins that bind IGF-I and IGF-II and modulate their biological activities.
1772 9369813 Insulin secretion was increased twofold in encapsulated rat islets exposed to prolactin compared with control values.
1773 9375806 The cytokine interleukin-1beta (IL-1beta) has been shown to inhibit insulin secretion and destroy pancreatic islets by a mechanism that involves the expression of inducible nitric oxide synthase (iNOS), and the production of nitric oxide (NO).
1774 9375806 We show that the interleukin-1 receptor antagonist protein (IRAP) prevents IL-1beta-induced nitrite formation and IL-1beta-induced inhibition of insulin secretion by isolated islets and primary beta-cells purified by fluorescence-activated cell sorting (FACS).
1775 9388085 Among patients starting insulin therapy, hemoglobin A1c (HbA1c) decreased by 0.9 percentage point (95% confidence interval, 0.7-1.0) at 1 year compared with those receiving stable medication regimens; however, 2 years after starting insulin therapy, 60% still had HbA1c levels of 8% or greater.
1776 9388210 IGFBP-7 blocks insulin binding to the insulin receptor and thereby inhibiting the earliest steps in insulin action, such as autophosphorylation of the insulin receptor beta subunit and phosphorylation of IRS-1, indicating that IGFBP-7 is a functional insulin-binding protein.
1777 9388210 Like IGFBP-7, an NH2-terminal fragment of IGFBP-3 (IGFBP-3((1-87))), also binds insulin with high affinity and blocks insulin action.
1778 9388272 Prolonged insulin treatment resulted in decreased expression of both ErbB2 and ErbB3.
1779 9388374 Levels of collagen alpha1(1) mRNA were also increased by both insulin and IGF-1.
1780 9388398 Variable adherence to insulin treatment is thought to contribute to poor glycaemic control, diabetic ketoacidosis, and brittle diabetes in adolescents and young adults with IDDM.
1781 9389501 Insulin inhibits the increase in heregulin beta1 binding, as well as the increase in ErbB3 messenger RNA and protein.
1782 9389501 Using chemical activators or antagonists, we sought to identify the signaling pathways that link insulin to ErbB3 expression.
1783 9389501 The PI-3 kinase inhibitors, wortmannin and LY294002, completely blocked the inhibition of ErbB3 protein expression by insulin, suggesting a role for PI-3 kinase in the regulation of this growth factor receptor.
1784 9389501 Rapamycin, an inhibitor of p70 S6 kinase, an enzyme downstream of PI-3 kinase, failed to block the effect of insulin on ErbB3 expression.
1785 9389736 In all cases, mouse leptin inhibited insulin secretion at concentrations within the plasma range reported in humans.
1786 9392477 Furthermore, TNF-alpha has distinct effects on adipose tissue including induction of insulin resistance, induction of leptin production, stimulation of lipolysis, suppression of lipogenesis, induction of adipocyte dedifferentiation, and impairment of preadipocyte differentiation in vitro.
1787 9392479 The clinical use of ACE inhibitors has been associated with increased insulin sensitivity.
1788 9392479 Insulin stimulation increased receptor autophosphorylation to 462 +/- 253% (P < 0.05) in the liver and 697 +/- 78% (P < 0.001) in the muscle of ACE inhibitor-treated rats.
1789 9392479 These data demonstrate that ACE inhibitors modulate the early steps of insulin signaling, and that this effect may be simulated by the administration of bradykinin.
1790 9392481 The insulin-induced increment in 3-O-methylglucose transport was strongly correlated with the insulin-induced increase in cell surface GLUT4 content (r2 = 0.91; P < 0.005).
1791 9392495 Three weeks after induction of diabetes, we measured renal kallikrein and renin mRNA levels, renal kallikrein and renal renin activity, and plasma renin activity in control and diabetic rats and diabetic rats treated with insulin or IGF-I for 2 or 5 h.
1792 9392495 These data suggest that 1) diabetes suppresses kallikrein and renin gene expression, and these abnormalities are reversed by insulin or IGF-I; and 2) the diabetic state produces resistance to IGF-I induction of kallikrein and renin gene expression.
1793 9392506 In soleus muscle from GK rats, maximal insulin-stimulated (120 nmol/l) Akt kinase activity was reduced by 68% (P < 0.01) and glucose transport was decreased by 39% (P < 0.05), compared with Wistar rats.
1794 9392506 At a submaximal insulin concentration (2.4 nmol/l), activity of Akt kinase and glucose transport were unaltered.
1795 9392506 In conclusion, improved glucose tolerance in diabetic GK rats by phlorizin treatment fully restored insulin-stimulated activity of Akt kinase and glucose transport.
1796 9394314 Following a randomized block design, controlled versus placebo, we investigated, in insulin-dependent diabetic patients with micro- or macroalbuminuria, whether GAG therapy can influence an altered albumin excretion rate (AER).
1797 9396242 Therefore, we designed a study to determine: (1) the effect of TNF-alpha on insulin sensitivity, and (2) the effect of LPD on the TNF-alpha response and the risk factors of atherosclerosis, such as insulin sensitivity and lipid metabolism, in patients with diabetic renal failure.
1798 9396242 These results indicate that: (1) TNF-alpha derived from PBMCs might affect insulin sensitivity in patients with diabetic renal failure, and (2) LPD does not have any significant effect on the risk factors of atherosclerosis.
1799 9397146 The observations that GLP-1 induces both secretion and production of insulin, and that its activities are mainly glucose-dependent, led to the suggestion that GLP-1 may present a unique advantage over sulfonylurea drugs in the treatment of NIDDM.
1800 9397296 A recent 1-year randomized double-blind study in hypertensive insulin-dependent diabetic patients with diabetic nephropathy showed a more beneficial effect on the decline rate in the glomerular filtration rate of nisoldipine (long-acting dihydropyridine) than angiotensin-converting-enzyme (ACE) inhibition.
1801 9398728 In cultured adipocytes, leptin is increased by insulin and decreased by cAMP.
1802 9398728 In animal models, insulin and agents that increase intracellular cAMP have been shown to similarly affect plasma leptin in vivo.
1803 9398740 This observation led to the hypothesis that these amino acid substitutions may impair the function of IRS-1, thereby causing the insulin resistance seen in patients with NIDDM.
1804 9399957 During physiologic hyperinsulinemia (insulin clamp), leptin markedly enhanced insulin action on both inhibition of hepatic glucose production and stimulation of glucose uptake.
1805 9399964 This results in differential decreases in IRS-1 and IRS-2 phosphorylation, docking of the p85alpha regulatory subunit of PI 3-kinase, and activation of this enzyme in these two insulin target tissues.
1806 9399964 Thus, there are multiple alterations in the early steps of insulin signaling in the ob/ob mouse, with differential regulation of IRS-1 and IRS-2, various PI 3-kinase regulatory isoforms, and a lack of compensation for the decrease in insulin signaling by any of the known alternative pathways at these levels.
1807 9400384 The change in PKC epsilon distribution and in TnI phosphorylation in diabetic animals was completely prevented by rendering the animals euglycemic with insulin or by concomitant treatment with a specific angiotensin II type-1 receptor (AT1) antagonist.
1808 9402951 Although hyperketonemia and/or altered growth hormone secretion caused by diabetes have been implicated in enhanced CYP2E1, 2B, 3A and 4A expression, the effect of insulin on hepatic P450 expression, in the absence of associated metabolic/hormonal alterations, remains unknown.
1809 9402951 Maintaining primary rat hepatocytes in culture in the absence of insulin for 48, 72, or 96 h increased CYP2E1 mRNA levels 5-, 11-, and 4-fold, respectively, relative to cells maintained in the presence of the standard concentration of 1 microM insulin.
1810 9402951 Concentration-response studies revealed that decreasing the concentration of insulin below 10 nM (i.e. 1 nM, 0.1 nM, no insulin) increased CYP2E1 mRNA levels 4-, 7-, and 11-fold, respectively.
1811 9402951 CYP3A mRNA levels were unaltered and CYP4A mRNA levels were decreased marginally (approximately 50%) by the absence of insulin relative to levels in cells cultured in the presence of 1 microM insulin over 96 h in culture.
1812 9402951 The results of this study provide evidence that insulin itself, in the absence of other diabetes-induced metabolic or hormonal alterations, affects CYP2E1 and 2B, but not CYP3A or 4A, expression in primary cultured rat hepatocytes.
1813 9402951 Furthermore, CYP2E1 expression is differentially regulated by insulin relative to CYP2B, 3A or 4A.
1814 9441763 LMX1 is a LIM-homeodomain (LIM-HD)-containing protein expressed selectively in insulin-producing beta-cell lines, and it it has been shown to activate insulin gene transcription.
1815 9548472 Evidence in this paper indicates that insulin can down-regulate the inducible nitric oxide synthase (iNOS) pathway in vivo.
1816 9405294 Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats.
1817 9421367 Leptin exposure (300 ng/ml) for 2 h did not alter the basal, submaximal, or maximal response of glucose transport to insulin in skeletal muscle (1.50 +/- 0.14, 4.76 +/- 0.58, and 9.04 +/- 1.09 micromol x ml-1 x h-1 for 0, 0.6, and 12.0 nmol/l insulin, respectively).
1818 9421367 Similar to our findings in the epitrochlearis muscle, leptin had no direct effect on basal or insulin-stimulated glucose uptake in soleus muscle from ob/ob or lean mice or adipocytes from normal mice.
1819 9421368 We previously reported that insulin induces the translocation of GLUT4 to both the plasma membrane and the transverse tubules (T-tubules) in rat skeletal muscle (Am J Physiol 270:E667-E676, 1996).
1820 9421368 Surprisingly, insulin increased plasma membrane GLUT4 content to comparable levels in control and diabetic rat skeletal muscle.
1821 9421370 C2-ceramide inhibited insulin-stimulated glucose uptake after 2 h by decreasing insulin-induced translocation of GLUT1 and GLUT4 to plasma membranes.
1822 9421370 Incubation for 24 h with tumor necrosis factor-alpha (TNF-alpha) but not C2-ceramide decreased the concentration and insulin-induced tyrosine phosphorylation of IRS-1 in this experimental system.
1823 9421372 We concluded that oral administration of insulin can induce the presence of regulatory T-cells in the pancreas and the corresponding draining lymph nodes, initiate the secretion of IL-4 in this microenvironment sufficiently to suppress the activity of Th1 autoreactive T-cell clones, and ultimately provide protection against autoimmune diabetes.
1824 9421373 To assess the effects of GLP-1 on the mass, frequency, amplitude, and overall contribution of pulsatile insulin secretion, we used a recently validated deconvolution model to examine these variables before and during infusion of GLP-1 in eight healthy men (age 28 +/- 2 years; BMI 24 +/- 2 kg/m2).
1825 9421373 After GLP-1 infusion, there was an abrupt increase in the peripheral concentrations of serum C-peptide (696 +/- 65 vs. 1,538 +/- 165 pmol/l) and insulin (49 +/- 8 vs. 138 +/- 21 pmol/l) concentrations.
1826 9421373 This increase was mainly due to an increase in the pulsatile component of insulin secretion that was achieved by a fourfold increase in secretory burst mass (28.2 +/- 4.4 vs. 100.1 +/- 15.8 pmol x l-1 x pulse-1; P < 0.001), and amplitude (12.7 +/- 2.2 vs. 4.3 +/- 7.7 pmol x l-1 x min-1; P < 0.002), whereas the secretory burst frequency was not affected by GLP-1 (11.5 +/- 0.7 vs. 12.6 +/- 0.6 pulses/h; P = 0.4).
1827 9421374 The STZ-induced reduction of GLUT2 protein and mRNA was not due to an essential loss of beta-cells, because ex vivo, not only the total RNA yield and protein content in isolated islets, but also proinsulin mRNA expression, failed to differ significantly in the differently treated groups.
1828 9421380 The effect on gastric emptying of hypoglycemia induced by a 5 mU/min insulin infusion (t = 5-90 min) was assessed in conscious rats continuously infused with amylin (50 pmol x kg-1 x min-1; t = -30 to 90 min).
1829 9421381 Perhaps consistent with a less efficient insulin signaling, a twofold reduction in GLUT4, glycogen synthase, and leptin mRNA expression was observed in omental adipose tissue.
1830 9421383 This disturbance is closely linked to iatrogenic hyperinsulinemia and the nonphysiologic stimulation of lipoprotein lipase (LpL), a physiologic activator of CET, because lowering systemic insulin levels by administering insulin through the intraperitoneal insulin route normalizes LpL and CET.
1831 9421388 After 4 days of culture, the cytokeratin 19+ ductal cells exhibited a BrdU-labeling index of 30% (P < 0.01 vs. 2% without HGF and matrix), whereas <0.1% of insulin-positive and <1% of glucagon-positive cells were labeled.
1832 9421397 Because ascorbate also influences osteoblast differentiation and is a cofactor for collagen synthesis, we examined the effects of insulin on the transport and metabolism of vitamin C in osteoblastic cells.
1833 9468528 Insulin-like growth factor-I (IGF-I) receptors activate divergent signaling pathways by phosphorylating multiple cellular proteins, including insulin receptor substrate-1 (IRS-1) and the Shc proteins.
1834 9516660 In the present study, the effect of insulin treatment on this increased ACE activity in the STZ-diabetic rat was investigated.
1835 9516660 Insulin treatment reduced lung ACE activity to values similar to those observed in non-diabetic rats.
1836 9516660 In summary, insulin administration to hyperglycaemic rats resulted in a reduction in the enhanced serum and lung ACE activity to values seen in non-diabetic rats.
1837 9519708 GLP-1 regulates blood glucose via stimulation of glucose-dependent insulin secretion, inhibition of gastric emptying, and inhibition of glucagon secretion.
1838 9519710 Englitazone did not increase IR, IRS-1/IRS-2, pp60, or MAPK phosphorylation, nor did it enhance insulin's stimulation of these parameters.
1839 9519716 Recent studies demonstrated that leptin receptor mRNA is expressed in pancreatic islets of rodents and that leptin at relatively high doses inhibits glucose-induced insulin secretion from rat islets.
1840 9519716 In this study, we report that leptin inhibits glucose-induced insulin secretion at lower concentrations ranging from 25 to 50 ng/ml using a static incubation method.
1841 9519716 Leptin did not affect insulin secretion stimulated by glibenclamide (1 and 5 micromol/l) or forskolin (1 micromol/l).
1842 9519716 Leptin (50 ng/ml) significantly inhibited insulin secretion induced by the phorbol ester phorbol 12-myristate 13-acetate (TPA) in the presence of Ca2+ but not in the absence of Ca2+.
1843 9519718 In contrast, tenfold higher dosages of leptin had no effect on body weight, food intake, or circulating insulin or glucose concentrations of UCP-DTA mice.
1844 9519720 The aim of this study was to test the hypothesis that plasma leptin concentrations contributed to the pathophysiology of NIDDM by decreasing both insulin-mediated glucose disposal and glucose-stimulated insulin secretion.
1845 9519720 When this was done, the significant relationship between leptin and SSPG disappeared, whereas both BMI (P < 0.03) and insulin response (P < 0.001) were correlated with SSPG.
1846 9519730 Hypofibrinolysis caused by increased plasminogen activator inhibitor 1 (PAI-1) has been implicated in the vasculopathy of type 2 diabetes, typified by increased insulin, glucose, and triglycerides.
1847 9519730 However, short-term infusions of insulin have not increased PAI-1 in normal subjects.
1848 9519730 We hypothesized that induction of increased insulin accompanied by increased glucose and triglycerides would increase PAI-1.
1849 9519730 In contrast to results with infusion of saline alone (n = 16) and euglycemic-hyperinsulinemic clamps (n = 10, serum insulin = 89 +/- 7 microU/dl), PAI-1 in blood increased significantly 6 h after the onset of infusion (15 +/- 5 ng/ml, P < 0.05 vs. baseline = 7.4 +/- 1.1, saline 6 h = 3.4 +/- 1.1, and insulin alone 6 h = 3.7 +/- 0.8) and remained elevated for an additional 6 h (combined infusion = 13.8 +/- 3.8 ng/ml, saline = 6.7 +/- 2 ng/ml, insulin alone = 7.8 +/- 1.7 ng/ml, P = 0.06).
1850 9519744 In response to 40 mU insulin, HKII mRNA in lean control subjects was increased 1.48 +/- 0.18-fold (P < 0.05) but failed to increase significantly in the obese (1.12 +/- 0.24) or NIDDM (1.14 +/- 0.18) groups.
1851 9519744 In response to 240 mU insulin, HKII mRNA was increased in all groups (control subjects 1.48 +/- 0.18, P < 0.05 vs. basal, obese 1.30 +/- 0.16, P < 0.05, and NIDDM 1.25 +/- 0.14, P < 0.05).
1852 9519744 Resistance to insulin's metabolic effects extends to its ability to induce HKII expression in obesity and NIDDM.
1853 9519761 Overall, these data provide further evidence for an important role for LAR in the regulation of insulin action and glucose homeostasis in intact animals.
1854 9624446 Diabetes increased the expression of the nuclear antigen Ki-67 in fetal insular pancreas, and insulin treatment returned it to the normal state.
1855 9624635 Fasting leptin concentration correlated positively with BMI (r = 0.75, P < 0.001) and fasting insulin (r = 0.71, P < 0.01) in healthy men as well as with insulin level (r = 0.54, p < 0.05) in type 1 diabetic patients.
1856 9625290 In a cross-sectional study, 93 patients (known duration 17 +/- 8 years, mean+/-SD) with poor metabolic control (glycosylated hemoglobin, HbA1C 9.3%+/-2.09%) were evaluated for CHD, for insulin release (C-peptide), for clinical and metabolic parameters including body mass index (BMI), smoking habits, arterial blood pressure (BP), blood lipids, kidney function, and proteinuria.
1857 9625360 The data provide evidence that insulin may be of importance as a regulator of serum leptin levels in vivo not only in rodents but also in humans.
1858 9687545 In conclusion, in a rat model of diet-induced (57.5% sucrose and 14% lipids) insulin resistance, the addition of short-chain FOS prevented some lipid disorders, lowered fatty acid synthase activity in the liver and tended to raise this activity in the adipose tissue.
1859 9781314 However, the detailed mechanisms involved in the regulation of glucose transporter (GLUT4) translocation from intracellular compartments to the cell surface membrane in response to insulin and contractions in skeletal muscle are not well understood.
1860 9781315 Intense interest is now focused on whether reduced insulin-mediated glucose transport in muscle from NIDDM patients results from alterations in the insulin signal transduction pathway or from alterations in traffic and/or translocation of GLUT4 to the plasma membrane.
1861 9781316 Inhibition of NOS activity blunts contraction-stimulated glucose transport but has no effect on insulin-stimulated glucose transport.
1862 9795371 In the diabetic patients, we further determined serum levels of proinsulin, intact parathyroid hormone (PTH), 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and several biochemical bone markers, including osteocalcin (OSC), bone alkaline phosphatase (B-ALP), carboxy-terminal propeptide of type I procollagen (PICP), and type I collagen cross-linked carboxy-terminal telopeptide (ICTP).
1863 9843961 c-Cbl-associated protein (CAP) is a signaling protein that interacts with both c-Cbl and the insulin receptor that may be involved in the specific insulin-stimulated tyrosine phosphorylation of c-Cbl.
1864 9843961 The expression of CAP mRNA and proteins are increased in 3T3-L1 adipocytes by the insulin sensitizing thiazolidinedione drugs, which are activators of the peroxisome proliferator-activated receptor gamma (PPARgamma).
1865 9843961 This increased expression of CAP was accompanied by a potentiation of insulin-stimulated c-Cbl tyrosine phosphorylation.
1866 9844354 Insulin receptors interact at least with three cascade reactions, phosphorylating G proteins and IRS-1, that activate PLC "ras" and PI-3-K.
1867 9851784 It is concluded that 1) open flow microperfusion combined with the ionic reference technique enables frequent measurement of the sc lactate concentration; 2) sc adipose tissue is a significant source of lactate release in the postabsorbtive state as well as during hyperinsulinemic clamp conditions; and 3) insulin concentrations greater than 180 pmol/L have no further influence on adipocyte stimulation of sc adipose tissue with respect to lactate release.
1868 10052864 Recent evidence suggests that activation of novel isoforms of protein kinase C (PKC) by diacylglycerol may mediate at least part of the adverse impact of FFAs on muscle insulin sensitivity.
1869 10052864 Vitamin E and fish oil omega-3s, by promoting the activity of diacylglycerol kinase and inhibiting that of phosphatidate phosphohydrolase, should reduce diacylglycerol levels, thus accounting for their documented favorable impact on insulin sensitivity.
1870 10604185 The production of leptin and tumour necrosis factor alpha by adipocytes provides a novel means of feedback control of triacylglycerol production, leptin by decreasing appetite and tumour necrosis factor alpha by inducing insulin resistance.
1871 10606633 Freshly isolated islets from IRS-1 knockout mice and SV40-transformed IRS-1-deficient beta-cell lines exhibit marked insulin secretory defects in response to glucose and arginine.
1872 10606633 Furthermore, insulin expression is reduced by about 2-fold in the IRS-1-null islets and beta-cell lines, and this defect can be partially restored by transfecting the cells with IRS-1.
1873 10606633 These data provide evidence for an important role of IRS-1 in islet function and provide a novel functional link between the insulin signaling and insulin secretion pathways.
1874 10611300 Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes.
1875 10615224 The results demonstrate that early protein restriction enhances the capacity for adipocyte glucose uptake at high insulin concentrations, but dampens the response to insulin at low physiological concentrations.
1876 10619393 It is suggested that, through modulation of maternal insulin secretion and hepatic metabolism, leptin integrates maternal nutrient storage to the nutrient requirements of the fetus.
1877 10619408 The addition of insulin to serum-starved cells led to an increase in XPD mRNA levels in both CHO/neo and CHO/HIRc cells, in a time and dose dependent fashion.
1878 10619408 Moreover, inhibition of protein synthesis by cyclohexamide induced a marked degradation of XPD mRNA levels in insulin treated cells.
1879 10631549 In the nonobese diabetic mouse model, there is new evidence that insulin plays an important role: not only is it an antigen for pathogenic CD4+ T cells but also it is recognised by highly diabetogenic CD8+ T cells.
1880 10634963 The insulinotropic hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1), regulate insulin secretion to nutrient intake and constitute the endocrine arm of the entero-insular axis.
1881 10641146 The effects of insulin, sodium orthovanadate and a hypoglycemic plant material, Trigonella foenum graecum (fenugreek) seed powder were studied on the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in diabetic liver and kidney.
1882 10641147 The in vivo effects of insulin, and other insulino mimetic agents like vanadate and fenugreek (T. foenum graecum) were followed on the changes in the activities of creatine kinase in heart, skeletal muscle and liver of experimental diabetic rats.
1883 10641147 The effects of insulin and vanadate were comparable in restoring normoglycemia and the creatine kinase activities.
1884 10657496 This study investigates whether there is a change in the pattern of distribution of neuropeptides including calcitonin-gene-related peptide (CGRP), neuropeptide-Y (NPY), vasoactive intestinal polypeptide (VIP), cholecystokinin-octapeptide (CCK-8), substance P (SP), and islet peptides including insulin (INS), glucagon (GLU), somatostatin (SOM) and pancreatic polypeptide (PP) in the pancreas of streptozotocin (STZ)-diabetic rats.
1885 9917528 B2-receptors are suggested to be involved in part of the renoprotective effects of angiotensin converting enzyme (ACE)-inhibitors in insulin-dependent diabetes.
1886 10842668 Insulin-stimulated phosphorylation of tyrosine residues on the insulin receptor and on the associated docking protein IRS-1 are reduced in skeletal muscle and liver compared to SHR, due mainly to diminished expression of insulin receptor and IRS-1 proteins.
1887 9854185 LY 294002, a specific inhibitor of PI-3 kinase, markedly decreased the basal rate of protein synthesis and completely prevented insulin-mediated stimulation of this process both in control and diabetic rats.
1888 9854185 Thus, PI-3 kinase is required for insulin-stimulated muscle protein synthesis in diabetic rats as in the controls.
1889 9854185 Neither basal nor insulin-stimulated p70(S6K) activity, a signalling element lying downstream of mTOR, were modified by STZ-diabetes.
1890 10027576 Steady state apolipoprotein(a) mRNA concentrations paralleled the decrease in apolipoprotein(a) synthesis (-29% after incubating the cells for 48 h with 100 nmol/l insulin) indicating that the decreased synthesis is regulated at the (post)-transcriptional level.
1891 10212230 Treatment of rat islets with poly(IC) + interferon-gamma (IFN-gamma) stimulates the time- and concentration-dependent expression of iNOS and production of nitrite by rat islets. iNOS expression and nitrite production by rat islets in response to poly(IC) + IFN-gamma correlate with an inhibition of insulin secretion and islet degeneration, effects that are prevented by the iNOS inhibitor aminoguanidine (AG).
1892 10212230 Treatment of macrophage-depleted rat islets for 40 h with poly(IC) + IFN-gamma results in the expression of iNOS, production of nitrite, and inhibition of insulin secretion.
1893 10212230 Poly IC + IFN-gamma stimulates iNOS expression and inhibits insulin secretion by primary beta-cells purified by fluorescence-activated cell sorting.
1894 10212230 These results indicate that dsRNA + IFN-gamma interacts directly with beta-cells stimulating iNOS expression and inhibiting insulin secretion in a nitric oxide-dependent manner.
1895 10233022 Proopiomelanocortin (POMC) mRNA in arcuate nucleus (Arc) and pituitary decreased in diabetes and normalized after insulin treatment.
1896 10233022 Diabetes did not alter proenkephalin (proEnk) expression in the Arc or pituitary, nor dynorphin A1-17 or beta-endorphin in paraventricular nucleus (PVN). alpha-Melanocyte-stimulating hormone (alpha-MSH) peptide levels were decreased in the PVN and normalized following insulin treatment.
1897 10233022 In experiment 2, insulin (2.5 IU/kg sc) daily for 1 wk in normal rats increased Arc POMC mRNA, but not proDyn and proEnk mRNA.
1898 10430617 Carriers of the Arg(972) substitution are characterized by lower fasting insulin and C-peptide levels compared with non-carriers, suggesting that the Arg(972) IRS-1 variant may contribute to impairment of insulin secretion.
1899 10430617 In this study, we stably overexpressed both wild-type IRS-1 (RIN-WT) and Arg(972) IRS-1 variant (RIN-Arg(972)) in RIN beta cells to investigate directly whether the polymorphism in codon 972 of IRS-1 impairs insulin secretion.
1900 10430617 The Arg(972) IRS-1 variant did not alter the extent of either glucose- or insulin-stimulated tyrosine phosphorylation of recombinant IRS-1.
1901 10430617 By contrast, RIN cells expressing Arg(972) IRS-1 exhibited a marked decrease in both glucose- and sulfonylurea-stimulated insulin secretion compared with RIN-WT.
1902 10525663 The proportion of fibrillar amyloid (amyloid area/islet area%) correlated with the amount of insulin (r = 0.55, p < 0.05) and IAPP (r = 0.5, p < 0.05) in the culture media.
1903 10525669 The protracted effect is due primarily to albumin binding of the insulin analogue NN304.
1904 10700396 Liver pyruvate kinase activity and blood insulin also decreased after lithium administration.
1905 10799317 KRP 297, which has been reported to be a PPARalpha and gamma co-activator, also affected serum triglycerides and insulin in fatty Zucker rats although no change in body weight gain was noted.
1906 10802154 Our results clearly demonstrated that bradykinin enhanced insulin-stimulated tyrosine kinase activity of the insulin receptor and downstream insulin signal cascade through the BK2R mediated signal pathway.
1907 10807873 Furthermore, Western blot analysis demonstrated that insulin increased MMP-12 protein production.
1908 10811153 Among patients with normal baseline serum potassium, the factors of age, presence of coronary disease or diabetes, comorbidity, the use of ACE inhibitors, loop diuretics, digitalis, corticosteroids, or insulin, and baseline serum potassium were associated with incident hypokalemia in initial models.
1909 10811851 Expression of an IRS-1 mutant (IRS-1Deltap85) lacking the binding site for the p85 subunit of phosphatidylinositol 3-kinase (PI3K) also restored insulin sensitivity, although PI3K is known to play a crucial role in insulin's metabolic responses.
1910 10811851 These data suggest that PKB in liver plays a pivotal role in systemic glucose homeostasis and that PKB activation might be sufficient for reducing insulin resistance even without full activation of PI3K.
1911 10813377 In vascular smooth muscle cells (VSMCs), insulin transduces a mitogenic signal that is dependent on the ERK1/2 MAP kinases.
1912 10813377 Neither early steps in insulin signaling nor the phosphatidylinositol 3-kinase (PI3K) branch of this pathway were affected by TRO, because it had no effect on IRS-1 phosphorylation, PI3K/IRS-1 association, or Akt phosphorylation.
1913 10748204 However, only the MEF2A protein was selectively down-regulated in insulin-deficient diabetes.
1914 10748204 These data strongly suggest that the MEF2A-MEF2D heterodimer is selectively decreased in insulin-deficient diabetes and is responsible for hormonally regulated expression of the GLUT4 gene.
1915 10749857 We evaluated effects of the thiazolidinedione, rosiglitazone, on insulin-induced activation of protein kinase C (PKC)-zeta/lambda and glucose transport in adipocytes of Goto-Kakizaki (GK)-diabetic and nondiabetic rats.
1916 10751417 Compared with control cells, cells expressing high levels of PTP1B showed a 50-60% decrease in maximally insulin-stimulated tyrosyl phosphorylation of IR and insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) activity associated with IRS-1 or with phosphotyrosine.
1917 10751417 Overexpression of PTP1B had no effect on basal, submaximally or maximally (100 nm) insulin-stimulated glucose transport or on the EC(50) for transport.
1918 10751417 Our results suggest that: 1) insulin stimulation of glucose transport in adipocytes requires
1919 10764814 Insulin binding to the insulin receptor (IR) triggers its autophosphorylation, resulting in phosphorylation of Shc and the downstream activation of p42/p44 extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2), which mediates insulin-induced proliferation in vascular smooth muscle cells (VSMC).
1920 10764814 Since insulin resistance is a risk factor for vascular disease, we examined the effects of TNFalpha on mitogenic signaling by insulin.
1921 10764814 Preincubation (30-120 min) with TNFalpha had no effect on insulin-induced IR phosphorylation.
1922 10764814 In contrast, TNFalpha transiently suppressed insulin-induced ERK1/2 activation.
1923 10764814 Thus, TNFalpha selectively interferes with insulin-induced mitogenic signaling by inhibiting the phosphorylation of Shc and the downstream activation of ERK1/2.
1924 10862609 Preincubation of oocytes for >4 h with insulin (1 micrometer) augmented GLUT4 transport of 2-DG and DHA by up to 5-fold.
1925 10966857 Our scant knowledge in this area is confined mostly to a descriptive account of the fate of the major secreted components, principally insulin and the enzymes PC1, PC2, and CPH involved in the proteolytic conversion of proinsulin to insulin.
1926 10969838 CLA supplementation decreased blood leptin levels, but continuous leptin infusion reversed hyperinsulinemia, indicating that leptin depletion contributes to the development of insulin resistance.
1927 10969840 GLP-1 stimulates insulin biosynthesis, secretion, and islet growth, whereas leptin inhibits glucose-dependent insulin secretion and insulin gene transcription.
1928 10969840 These findings illustrate that although leptin and GLP-1 actions overlap in the brain and endocrine pancreas, disruption of GLP-1 signaling does not modify the response to leptin or the phenotype of leptin deficiency in the ob/ob mouse, as assessed by long-term control of body weight or the adaptive beta-cell response to insulin resistance in vivo.
1929 10971546 In conclusion, insulin treatment of patients with poorly controlled non-insulin-dependent diabetes mellitus increased the fast-twitch fibre area, reduced myoglobin levels and decreased muscle enzyme activity related to fatty acid oxidation.
1930 10973497 Insulin negatively regulates expression of the insulin-like growth factor binding protein 1 (IGFBP-1) gene by means of an insulin-responsive element (IRE) that also contributes to glucocorticoid stimulation of this gene.
1931 10974195 Furthermore, when fed a high fat diet, these mice maintained insulin sensitivity and were resistant to obesity, suggesting that inhibition of PTP-1B activity could be a novel way of treating type 2 diabetes and obesity.
1932 10976915 Insulin-mediated MBP activation was accompanied by a rapid time-dependent reduction in the phosphorylation state of the myosin-bound regulatory subunit (MBS) of MBP.
1933 10976915 The decrease observed in MBS phosphorylation was due to insulin-induced inhibition of Rho kinase activity.
1934 10976915 Insulin also prevented a thrombin-mediated increase in Rho kinase activation and abolished the thrombin-induced increase in MBS phosphorylation and MBP inactivation.
1935 10976915 These data are consistent with the notion that insulin inactivates Rho kinase and decreases MBS phosphorylation to activate MBP in VSMCs.
1936 10976915 Furthermore, treatment with synthetic inhibitors of phosphatidylinositol-3 kinase (PI3-kinase), nitric oxide synthase (NOS), and cyclic guanosine monophosphate (cGMP) all blocked insulin's effect on MBP activation.
1937 10976915 We conclude that insulin stimulates MBP via its regulatory subunit, MBS partly by inactivating Rho kinase and stimulating NO/cGMP signaling via PI3-kinase as part of a complex signaling network that controls 20-kDa myosin light chain (MLC20) phosphorylation and VSMC contraction.
1938 10976920 Such selective PPARgamma antagonists may help determine whether insulin sensitization by thiazolidinediones is mediated solely through PPARgamma activation, and whether there are PPARgamma-ligand-independent pathways for adipocyte differentiation.
1939 10976920 If selective PPARgamma modulators block adipogenesis in vivo, they may prevent obesity, lower insulin resistance, and delay the onset of type 2 diabetes.
1940 10981244 We evaluated four subgroups and found that patients with hypertension had fewer adverse renal outcomes if they were receiving ACE inhibitors whether they were taking (p = 0.0006) or not taking insulin (p = 0.047).
1941 10984107 Under-representation of arachidonate-containing GPC and GPE species in some fa/fa rat tissues at 6 wk could contribute to insulin resistance, but depletion of islet arachidonate-containing GPC and GPE species is unlikely to explain the evolution of the insulin secretory defect that is well-developed by 12 wk of age.
1942 10989952 It generates insulin-like signals for glucose transport and glycogen synthesis via leptin receptors and the PI3-kinase and could, therefore, play a role as a mediator of obesity-related insulin resistance.
1943 10990079 The glucagon-receptor antagonist also suppressed the potentiation of glucose-induced insulin release by addition of 10 nmol/l glucagon.
1944 10990085 Altered fetal insulin secretion caused by fetal or maternal glucokinase mutations influence birth weight.
1945 10940302 Insulin activates a complex set of intracellular responses, including the activation of mitogen-activated protein kinases Erk1,2.
1946 10940302 The counterregulatory actions of insulin on catecholamine action are well known and include phosphorylation of the beta(2)-adrenergic receptor on Tyr(350), Tyr(354), and Tyr(364) in the C-terminal cytoplasmic domain, as well as enhanced sequestration of the beta(2)-adrenergic receptor.
1947 10940302 In Chinese hamster ovary cells, expression of beta(2)-adrenergic receptors enhanced 5-10-fold the activation of Erk1,2 by insulin and prolonged the activation, the greatest enhancement occurring at 5 min post-insulin.
1948 10940302 The potentiation of insulin signaling on Erk1,2 was proportional to the level of expression of beta(2)-adrenergic receptor.
1949 10940302 Blockade of beta(2)-adrenergic receptor sequestration does not alter the ability of the beta(2)-adrenergic receptor to potentiate insulin action on Erk1,2.
1950 10967106 The decrease in glucose-stimulated insulin secretion induced by IL-1beta and IFN-gamma was however not prevented.
1951 10967106 This was because these dysfunctions were induced by IFN-gamma alone, which decreased cellular insulin content and stimulated insulin exocytosis.
1952 10967113 Islets or INS(832/13) beta-cells exposed to high glucose show a 60-80% reduction in PPARalpha mRNA expression.
1953 10967116 We recently described the identification of a non-peptidyl fungal metabolite (l-783,281, compound 1), which induced activation of human insulin receptor (IR) tyrosine kinase and mediated insulin-like effects in cells, as well as decreased blood glucose levels in murine models of Type 2 diabetes (Zhang, B., Salituro, G., Szalkowski, D., Li, Z., Zhang, Y., Royo, I., Vilella, D., Diez, M.
1954 11024042 However, LPL synthetic rate, measured using [(35)S]methionine pulse labeling, was decreased by 75% in the diabetic adipocytes, and insulin treatment reversed this effect.
1955 11108733 Insulin responses to the test meals tended to be higher in Thr54 homozygotes, but glucose and triglyceride responses were not different.The results of this study suggest that the Thr54 form of IFABP is associated with higher and prolonged NEFA responses to dietary fat in vivo.
1956 11110661 A tumor-derived K-cell line was induced to produce human insulin by providing the cells with the human insulin gene linked to the 5'-regulatory region of the gene encoding glucose-dependent insulinotropic polypeptide (GIP).
1957 11117522 PDX-1 binds to and transactivates the promoters of several physiologically relevant genes within the beta-cell, including insulin, glucose transporter 2, glucokinase, and islet amyloid polypeptide.
1958 11117522 This study focuses on the mechanisms by which PDX-1 activates insulin gene transcription.
1959 11117522 These results suggest that the PDX-1 transactivation domain is specifically required for appropriate regulation of insulin enhancer function in beta-cells.
1960 11136544 The findings in FPLD indicate that defective structure of the nuclear envelope produces a phenotype of insulin resistance.
1961 11137300 PTP-1B is a ubiquitously expressed intracellular protein tyrosine phosphatase (PTP) that has been implicated in the negative regulation of insulin signaling.
1962 11138783 Autoimmune diseases like multiple sclerosis (MS) and insulin-dependent diabetes (IDD) are believed to be mediated by pathogenic CD4+ autoreactive T cells which mediate selective destruction of specific host cells.
1963 10861205 Insulin stimulates the transcription of the sterol regulatory- element binding protein (SREBP) 1/ADD1 gene in liver.
1964 10861205 Hepatocytes in primary culture were used to delineate the insulin signalling pathway for induction of SREBP1 gene expression.
1965 10861205 Thus acute activation of PKB is sufficient to induce SREBP1 mRNA accumulation in primary hepatocytes, and might be the major signalling event by which insulin induces SREBP1 gene expression in the liver.
1966 10927633 Primary human fibroblasts, myoblasts and stabilized cell lines (HepG2 and NIH3T3) were transduced either with a retroviral vector coding for wild-type proinsulin or for a genetically mutated one, carrying cleavage sites sensitive to furin.
1967 10995595 TNF-alpha impairs insulin-mediated glucose uptake in adipocytes, but because of lipolytic effects the interpretation of clinical studies and the extent to which TNF-alpha affects muscle insulin sensitivity are unclear.
1968 10995595 The present study investigated the effects of TNF-alpha and a PKC inhibitor (RO-318220) on basal and insulin-stimulated 2-[(3)H]deoxyglucose uptake in cultured L6 myoblasts.
1969 10995595 Incubation with TNF-alpha at 1 or 10 ng/ml for 24 h had no significant effect on basal glucose uptake, insulin sensitivity or maximal insulin responsiveness.
1970 10995595 In conclusion, although increased TNF-alpha expression and plasma concentrations have been implicated in the pathogenesis of insulin resistance in various clinical states, there is no evidence that TNF-alpha impairs insulin-stimulated glucose uptake in a skeletal-muscle-derived cell line.
1971 10878750 Importantly, results from knockout mice deficient in TNF-alpha or its receptors have suggested that TNF-alpha has a role in regulating in vivo insulin sensitivity.
1972 10878750 These include the downregulation of genes that are required for normal insulin action, direct effects on insulin signaling, induction of elevated free fatty acids via stimulation of lipolysis, and negative regulation of PPAR gamma, an important insulin-sensitizing nuclear receptor.
1973 11042466 These compounds appear to enhance insulin action by modulating the activity of the nuclear receptor peroxisome proliferator-activated receptor (PPAR) gamma.
1974 11024034 Furthermore, overexpression of STAT-1 alpha does not impair robust glucose-stimulated insulin secretion in the INS-1-derived cell line 832/13.
1975 11147775 The generation of small adipocytes, presumably mediated by increased expression of UCP-1 in addition to increased lipolysis in response to AJ-9677, was associated with decreased TNF-alpha and free fatty acid production and may be the mechanism of amelioration of insulin resistance in KK-Ay/Ta diabetic obese mice.
1976 11147776 To explore whether AICAR also affects insulin-stimulated glucose transport and GLUT4 cell surface content, Wistar rats were subcutaneously injected with AICAR for 5 days in succession (1 mg/g body wt).
1977 11147776 In conclusion, 5 days of AICAR administration induces a pronounced fiber type-specific increase in insulin-stimulated glucose uptake and GLUT4 cell surface content in rat skeletal muscle with the greatest effect observed on white fast-twitch glycolytic muscles (EPI).
1978 11147789 This interval contains the gene for protein tyrosine phosphatase receptor type R (PTPRR)--a protein that may be involved in both insulin secretion and action.
1979 11147790 In this study, we have investigated the early events in the insulin pathway that trigger the degradation of IRS-1.
1980 11147790 Incubation of the adipocytes with insulin induced a fast electrophoretic mobility shift of IRS-1 and a subsequent degradation of the protein.
1981 11147790 Treatment of the cells with the tyrosine phosphatase inhibitor orthovanadate in the presence of insulin or okadaic acid partially inhibited the degradation of IRS-1.
1982 11147790 Thus, regulation of serine/threonine versus tyrosine phosphorylation may modulate IRS-1 degradation, affecting insulin sensitivity.
1983 11147795 Because the acute addition of FFAs also increases glucose-stimulated insulin secretion, these data suggest that the incretin function of GLP-1 may involve a major role for lipolysis in cAMP-mediated potentiation of secretion.
1984 11147798 Addition of the peptides to the insulin-secreting betaTC-3 cell line results in a marked inhibition of IL-1beta-induced c-jun and c-fos expression.
1985 11147799 Augmented IR tyr dephosphorylation by protein tyrosine phosphatases (PTPs) may contribute to insulin resistance.
1986 11148145 The insulin-induced translocation of Glut4 to the cell surface is essential for the maintenance of optimal blood glucose levels, and defects in this system are associated with insulin resistance and type II diabetes.
1987 11148145 In addition, the interaction of Csp1 with syntaxin 4 suggests that this Csp isoform may play a role in insulin-stimulated fusion of GSVs with the plasma membrane.
1988 11150869 To investigate the changes in leptin levels and the relationship between this substance and insulin and glucose in pregnant women with gestational-onset diabetes, we measured plasma leptin levels in the maternal peripheral vein of 17 healthy and 17 diabetic women at 29 and 33 weeks of gestation.
1989 11150869 We conclude that leptin levels are elevated in pregnant women with gestational diabetes, and its metabolism depends on insulin levels and the severity of diabetes.
1990 11158071 Change in insulin AUC correlated significantly with change in tPA antigen (r = 0.43, P = 0.03).
1991 11159819 GLP-1 controls blood glucose following nutrient absorption via stimulation of glucose-dependent insulin secretion, insulin biosynthesis, islet proliferation, and neogenesis and inhibition of glucagon secretion.
1992 11160042 Seven weeks of training significantly increased basal and insulin-stimulated ERK2 and RSK2 activities, as well as insulin stimulation of MAPK kinase activity.
1993 11160042 Therefore, 7 wk of training increases basal and insulin-stimulated ERK2 activity.
1994 11160134 Recently, we discovered that recombinant NH2-terminal Jun kinase phosphorylates IRS-1 at Ser307, which inhibits insulin-stimulated tyrosine phosphorylation of IRS-1.
1995 11160264 In this study, we have investigated the use of plasmid DNA (pDNA) vaccination to elicit Th2 effector cell function in an Ag-specific manner and in turn prevent insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. pDNA recombinants were engineered encoding a secreted fusion protein consisting of a fragment of glutamic acid decarboxylase 65 (GAD65) linked to IgGFc, and IL-4.
1996 11160826 In the absence of insulin, MHC-I molecules largely colocalize with the ER-resident protein calnexin and remain distinct from intracellular pools of GLUT4.
1997 11165687 The activity of superoxide dismutase, catalase and glutathione peroxidase and the level of insulin were decreased by 46% (from 1367+/-73 to 737+/-59 U/g Hb, P<0.001), 36% (from 2.3+/-0.3 to 1.4+/-0.1 U Bergmayera/g Hb, P<0.001), 31% (from 236+/-19 to 163+/-24 U/g Hb, P<0.001) and 91% (from 47.5+/-1.7 to 2.4+/-0.5 mU/l, P<0.001) respectively in rats treated with streptozotocin.
1998 11174836 Mutations of HNF-1alpha lead to severe beta cell dysfunction, resulting in decreased glucose-induced insulin secretion.
1999 11174836 Suppression of endogenous glucose production by insulin was blunted in MODY3 patients (3.3+/-1.2 micromol/kg per min) and in patients with NIDDM (4.4+/-0.6 micromol/kg per min) compared with controls (1.7+/-0.5 micromol/kg per min, P<0.05 compared with both MODY3 patients and patients with NIDDM).
2000 11177550 We constructed LhI*TFSN virus to encode a glucose-regulatable transforming growth factor alpha promoter controlling furin expression with a viral LTR promoter driving constitutive expression of furin-cleavable human proinsulin.
2001 11181061 Exposure to (IL-1 beta + IFN-gamma) had no effect on iNOS -/- islets except reducing the insulin content.
2002 11181516 An antiserum directed against the transcription factor islet duodenum homeobox-1 (IDX-1), a regulator of pancreas development and activator of the insulin gene promoter, attenuated the binding activity of Hh-responsive protein complexes.
2003 11181516 Nuclear IDX-1 protein levels on Western blots were increased by ectopic Hh expression, thereby providing a mechanism for Hh-mediated regulation of the insulin promoter.
2004 11181516 We propose that Hh signaling activates the insulin gene promoter indirectly via the direct activation of IDX-1 expression.
2005 11181517 IRBP binding to region V was competed by VmSp1, but not by VmAT, indicating specific interactions with the AT-rich sequence; insulin response elements from other genes also failed to compete.
2006 11181517 IRBP responded to as little as 10(-10) M insulin, indicating physiological relevance.
2007 11181517 As most insulin-responsive genes do not exhibit insulin-responsive nuclear factor binding, further studies of IRBP may also contribute to understanding of the mechanism of insulin action on gene transcription.
2008 11181571 Wolfram (DIDMOAD) syndrome is an autosomal recessive neurodegenerative disorder accompanied by insulin-dependent diabetes mellitus and progressive optic atrophy.
2009 11181905 In addition, SB-(+)-273779 antagonized CGRP-mediated 1) stimulation of intracellular Ca(2+) in recombinant CGRP receptors in HEK-293 cells, 2) inhibition of insulin-stimulated [(14)C]deoxyglucose uptake in L6 cells, 3) vasodilation in rat pulmonary artery, and 4) decrease in blood pressure in anesthetized rats.
2010 11201732 Moreover, treatment of normal mice with recombinant resistin impairs glucose tolerance and insulin action.
2011 11206403 Genetic variability in NEUROG3 is not associated with dominant Type I diabetes, MODY, Type II diabetes or changes in insulin secretion in the Danish Caucasians examined subjects.
2012 11206417 Haemodynamic effects of glucose and insulin were additive when somatostatin was co-administered but not under basal conditions.
2013 11096081 Insulin and insulin-like growth factor-1 stimulate activity of Sgk by a mechanism mediated by phosphoinositide-dependent kinases (PDK)-1 and -2.
2014 11108714 In combination, synthetic dsRNA (polyinosinic-polycytidylic acid, poly(I-C)) and interferon (IFN)-gamma stimulate inducible nitric-oxide synthase (iNOS) expression, inhibit insulin secretion, and induce islet degeneration.
2015 11108714 Interleukin-1 (IL-1) appears to mediate dsRNA + IFN-gamma-induced islet damage in a nitric oxide-dependent manner, as the interleukin-1 receptor antagonist protein prevents dsRNA + IFN-gamma-induced iNOS expression, inhibition of insulin secretion, and islet degeneration.
2016 11230363 P:eroxisome proliferator-activated receptor-gamma (PPARgamma) is a novel nuclear receptor, which enhances insulin-mediated glucose uptake.
2017 11250945 We demonstrated by Western blot analysis that levels of Sp1 and Sp3 proteins were increased more than 2-fold in the insulin-treated group.
2018 11250945 Additionally, the up-regulation of both Sp1 and Sp3 transcription factors by insulin was antagonized by tumor necrosis factor-alpha, a known inhibitor of insulin action.
2019 11250945 Immunohistochemical analysis demonstrated that H-411E cells treated with insulin (10,000 microU/ml) had a marked increase in demonstrable Sp1 in the nucleus compared with cells incubated in insulin-free medium.
2020 11250945 We demonstrated in rat liver tissue by both Western blot and immunohistochemical staining with anti-Sp1 antibody that 1) livers of fully diabetic streptozotocin rats have low levels of Sp1 transcription factor; and 2) insulin treatment of the diabetic rat rapidly reversed this process by markedly stimulating accumulation of Sp1 in rat liver.
2021 11250945 In summary, insulin stimulates Sp1 protein, a transcription factor that is shown to regulate calmodulin gene expression and most likely other, as yet untested, genes.
2022 11254901 The expression of endothelial nitric oxide synthase (eNOS) was significantly increased by chronic administration of insulin to diabetic rats.
2023 11255235 Reverse transcription-polymerase chain reaction and Northern blotting revealed that insulin induces the expression and transcriptional activity of the immediate early gene and zinc finger transcription protein, early growth response factor-1 (Egr-1).
2024 11255235 DNA synthesis induced by insulin was suppressed by inhibitors of two upstream activators of Egr-1, extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-phosphate (PI 3-K), whereas p38 kinase inhibitors had no effect.
2025 11257313 However, in the case of OLETF rats, leptin administration changed neither plasma insulin levels nor insulin-stimulated glucose uptake.
2026 11259670 Insulin also inhibited transcription of a reporter gene driven by the human IRS-2 promoter that was transfected into freshly isolated rat hepatocytes.
2027 11269655 GLUT4 mobilization from the intracellular pool in response to insulin was also investigated at 15 min after insulin injection.
2028 11269889 In this study, we focused on the cytotoxic activity of peripheral lymphocytes in patients with type 1 DM against the peptides of glutamic acid decarboxylase (GAD) and insulin, which can bind MHC class 1 A24.
2029 11269889 The results showed that cytotoxicity against insulin peptide binding to MHC class I A24 was observed in lymphocytes of four out of ten patients with type 1 DM.
2030 11270679 In our experiments, acetylcholinesterase was extracted from the fast extensor digitorum longus and slow soleus muscles of control, non-treated 6-week-diabetic and insulin-treated diabetic rats.
2031 11270684 The apolipoprotein C3-482C> T variant modulates insulin and glucose concentrations after an oral glucose tolerance test (OGTT) in young healthy white men.
2032 11270685 Nes2y cells, both variants showed about a 50% reduction in their ability to activate insulin gene transcription compared to wild-type IPF1, as measured by reporter gene assay.
2033 11274900 In male and female patients, leptin levels were significantly associated with body mass index (BMI), percent body fat, insulin level, triglyceride (TG) level, total abdominal fat area (TFA), visceral fat area (VFS), and subcutaneous fat area (SFA).
2034 11274905 Insulin stimulated GS activity was found to occur via a PI-3 kinase (PI-3K)-dependent pathway as wortmannin, an inhibitor of PI-3K, blocked insulin's ability to stimulate GS activity.
2035 11274905 After treatment with insulin (100 nM) for 5 min, cell extracts were assayed for IRS-1 associated and total PI-3K activity.
2036 11274905 At LG, insulin increased PI-3K activity by 43%.
2037 11274905 There was no insulin stimulation of PI-3K activity in cells cultured in HG or GlcN.
2038 11274905 At LG, insulin stimulated PKB activity.
2039 11274905 Again, both HG and GlcN significantly reduced insulin's ability to stimulate PKB activity.
2040 11274905 We conclude that the hexosamine-mediated insulin resistance of GS activity seen in rat-1 cells is mediated by hexosamine regulation of PI-3K and PKB.
2041 11277867 To employ hepatocytes as surrogate beta-cells for gene therapy of diabetes, a regulatory system was devised in this study by placing the human insulin cDNA under the control of the phosphoenolpyruvate carboxykinase (PEPCK) promoter, followed by the cytomegalovirus immediate early promoter-driven enhanced-green-fluorescent-protein open reading frame.
2042 11281851 Current strategies to treat diabetes include reducing insulin resistance using glitazones, supplementing insulin supplies with exogenous insulin, increasing endogenous insulin production with sulfonylureas and meglitinides, reducing hepatic glucose production through biguanides, and limiting postprandial glucose absorption with alpha-glucosidase inhibitors.
2043 11284388 Administration of specific DPPIV inhibitors closes this pathway of incretin degradation and greatly enhances insulin secretion.
2044 11287357 Adipose tissue expresses tumor necrosis factor (TNF) and interleukin (IL)-6, which may cause obesity-related insulin resistance.
2045 11287357 Thus the local expression of TNF and plasma IL-6 are higher in subjects with obesity-related insulin resistance.
2046 11288039 The beta(3)-adrenergic receptor (AR) gene variant (Trp64Arg) has been reported to be associated with obesity and insulin resistance in humans.
2047 11289032 Fasting plasma ghrelin was negatively correlated with percent body fat (r = -0.45; P = 0.01), fasting insulin (r = -0.45; P = 0.01) and leptin (r = -0.38; P = 0.03) concentrations.
2048 11289039 Insulin secretion is one of the functions mediated by CD38, a nonlineage pleiotropic cell surface receptor.
2049 11289042 Effects of GLP-1 on secretory mechanisms in type 2 diabetic patients and subjects with impaired glucose tolerance (IGT) known to have impaired pulsatile release of insulin have not yet been studied.
2050 11289042 By deconvolution analysis, insulin secretory burst frequency was not affected by GLP-1 in either type 2 diabetic patients (P = 0.15) or IGT subjects (P = 0.76).
2051 11289042 In conclusion, intravenous GLP-1 reduces plasma glucose in type 2 diabetic patients and improves the oscillatory secretion pattern by amplifying insulin secretory burst mass, whereas the oscillatory period determined by autocorrelation and spectral analysis is significantly prolonged.
2052 11289045 The data are compatible with a role of UCP2 and partial mitochondrial uncoupling in the decreased secretory response to glucose observed after chronic exposure of the beta-cell to elevated fatty acids, and suggest that the expression and/or activity of the protein may modulate insulin secretion in response to glucose.
2053 11289048 TLK16998 alone had no effect on IR signaling in mouse 3T3-L1 adipocytes but, at concentrations as low as 3.2 micromol/l, enhanced the effects of insulin on the phosphorylation of the IR beta-subunit and IR substrate 1, and on the amount of phosphatidylinositol 3-kinase that coimmunoprecipitated with IRS-1.
2054 11289049 In transfected MCF-7 cells, 125I-labeled insulin binding and IR content were unchanged, and PC-1 overexpression did not influence IGF-1 stimulation of IGF-1 receptor autophosphorylation.
2055 11289049 This interaction was greater for the Q allele than for the K allele (P < 0.01), suggesting that direct PC-1-IR interactions are important for the PC-1 inhibitory effect on insulin signaling.
2056 11289055 The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR)-gamma2 is associated with reduced transcriptional activity in vitro and increased insulin sensitivity in humans in vivo.
2057 11289057 Recent studies have identified a common proline-to-alanine substitution (Pro12Ala) in the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), a nuclear receptor that regulates adipocyte differentiation and possibly insulin sensitivity.
2058 11289470 In this study, we tested the primary hypotheses that previously described variants in the pancreatic sulfonylurea receptor gene (SUR1 or ABCC8), glucokinase (GCK) gene, or hepatocyte nuclear factor 1alpha (TCF1 or HNF1alpha) gene contribute to the inherited deficiencies of insulin secretion and beta-cell compensation to insulin resistance, as well as the secondary hypotheses that these variants altered insulin sensitivity.
2059 11289470 Unexpectedly, a variant in the 3' untranslated region of the GCK gene interacted significantly with BMI to predict insulin sensitivity.
2060 11289470 The exon 16 variant of the ABCC8 gene reduced beta-cell compensation to the decreased insulin sensitivity in the heterozygous state.
2061 11403855 Our objective was to determine whether Type 1 diabetic patients with microalbuminuria are less sensitive to the effects of insulin on glucose metabolism and skeletal muscle blood flow, compared to those with normal albumin excretion, after careful matching for confounding variables.
2062 11408416 A potential mechanism through which insulin can stimulate protein synthesis is modulation of the activity of eukaryotic initiation factor 2B (eIF2B).
2063 11410238 Tumor necrosis factor-alpha (TNF-alpha) is a key component of obesity-diabetes link, we therefore examined the attenuating effect of VO(opt)(2) on impaired insulin signal transduction induced by TNF-alpha.
2064 11410238 These results suggest that the anti-diabetic action of VO(opt)(2) is derived from an attenuation of a TNF-alpha induced impaired insulin signal transduction via inhibition of protein tyrosine phosphatase, providing a potential clinical utility for VO(opt)(2) in the treatment of NIDDM.
2065 11412137 Defects in insulin signal transduction through the insulin-receptor substrate-1/phosphatidylinositol 3-kinase pathway are associated with reduced insulin-stimulated glucose transporter 4 translocation and glucose transport activity in skeletal muscle from type II diabetic patients.
2066 11415857 Phosphodiesterase (PDE) 3B is a key enzyme involved in the anti-lipolytic action of insulin in adipocytes.
2067 11415857 PDE3B activation results in a reduced output of free fatty acids (FFA), whereas elevated serum FFA is known to cause insulin resistance.
2068 11416153 Using this assay, we demonstrate that both 3T3-L1 and CHO cells contain intracellular compartments from which GLUT4 is rapidly mobilized by insulin and that the initial magnitude and kinetics of redistribution to the plasma membrane are similar in these two cell types when they are cultured identically.
2069 11418698 We previously demonstrated that administration of plasmid DNAs (pDNAs) encoding IL-4 and a fragment of glutamic acid decarboxylase 65 (GAD65) fused to IgGFc induces GAD65-specific Th2 cells and prevents insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice.
2070 11418698 Surprisingly, young NOD mice receiving i.m. injections of pDNA encoding insulin B chain-IgGFc with or without IL-4 exhibited an accelerated progression of insulitis and developed early diabetes.
2071 11418698 Exacerbation of IDDM correlated with an increased frequency of IFN-gamma-secreting CD4(+) and CD8(+) T cells in response to insulin B chain-specific peptides compared with untreated mice.
2072 11418698 In contrast, treatment with pDNAs encoding insulin A chain-IgGFc and IL-4 elicited a low frequency of IL-4-secreting Th cells and had no effect on the progression of IDDM.
2073 11422429 It has been suggested that insulin has an effect on nerve regeneration similar to that of nerve growth factor (NGF).
2074 11422741 Immunohistology indicated that CTGF was expressed in renal cortex of diabetic rats, in contrast to controls in some tubular cross-sections, particularly dilated-appearing proximal tubules, in which it tended to colocalize with insulin-like growth factor-I (IGF-I).
2075 11423471 Accordingly, it can be suggested that in pancreatic beta-cells, AMPK also acts by decreasing HNF-4alpha protein level, and therefore insulin secretion.
2076 11423472 Among the factors responsible for the increases of PAI-1, insulin has recently attracted attention.
2077 11423472 Electrophoretic mobility shift assay identified three binding sites for insulin-induced factors, all colocalized with putative Sp1 binding sites.
2078 11423479 Together, our data provide evidence for a unique regulatory mechanism for the activation of ACC in the pancreatic beta-cell, leading to the generation of physiological signals that may be relevant for physiological insulin secretion.
2079 11423504 Islet cell antibodies >5 Juvenile Diabetes Foundation units were found in 10% of subjects, elevated insulin autoantibody levels in 4.6%, GAD antibody in 4.9%, and anti-tyrosine phosphatase-like protein autoantibodies in 3.9%.
2080 11423509 After adjustment for covariates including age, sex, C-peptide, waist circumference, and glucose tolerance status, fasting proinsulin concentration was significantly associated with concurrently measured lipid and apolipoprotein concentrations (triglycerides: r = 0.18, P < 0.0001; total cholesterol: r = 0.10, P = 0.02; LDL cholesterol: r = 0.11, P = 0.01; HDL cholesterol: r = -0.16, P = 0.0002; apolipoprotein (apo) B: r = 0.17, P < 0.0001; apoAI: r = -0.11, P = 0.008).
2081 11423509 In the adjusted prospective analysis, baseline triglycerides, HDL cholesterol, and apoB were associated with changes over time in proinsulin (r = 0.23, P = 0.04; r = -0.30, P = 0.01; r = 0.23, P = 0.04; respectively).
2082 11424232 ROI interfere with insulin signalling at various levels and are able to inhibit the translocation of GLUT4 in the plasma membrane.
2083 11427203 In both groups, HDL lipids, as well as plasma apo AI and PLTP activity decreased after 24 h of insulin (P<0.05 to P<0.01) compared to baseline and recovery, i.e. 1 week after insulin.
2084 11342531 Cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, and hormones, such as growth hormone, are known to cause insulin resistance, but the mechanisms by which they inhibit the cellular response to insulin have not been elucidated.
2085 11342531 SOCS-1 and SOCS-6 do not inhibit insulin-dependent IR autophosphorylation, but both proteins inhibit insulin-dependent activation of ERK1/2 and protein kinase B in vivo and IR-directed phosphorylation of IRS-1 in vitro.
2086 11342531 These results suggest that SOCS proteins may be inhibitors of IR signaling and could mediate cytokine-induced insulin resistance and contribute to the pathogenesis of type II diabetes.
2087 11342558 Here, using the highly differentiated beta Tc-Tet insulin-secreting cell line, we showed that IFN-gamma dose- and time-dependently suppressed insulin synthesis and glucose-stimulated secretion.
2088 11373275 Elevated levels of the hormone resistin, which is secreted by fat cells, are proposed to cause insulin resistance and to serve as a link between obesity and type 2 diabetes.
2089 11402048 Here we dissected mechanisms whereby insulin activates eNOS by using the fluorescent dye DAF-2 to directly measure NO production in single cells.
2090 11402048 However, cells expressing the eNOS-S1179A mutant (disrupted Akt phosphorylation site) did not produce detectable NO in response to insulin, whereas the response to LPA was similar to that observed in cells expressing wild-type eNOS.
2091 11402048 We conclude that insulin regulates eNOS activity using a Ca(2+)-independent mechanism requiring phosphorylation of eNOS by Akt.
2092 11509551 Our laboratory has recently demonstrated that insulin induces relaxation of vascular smooth muscle cells (VSMCs) by activating myosin-bound phosphatase (MBP) and by inhibiting Rho kinase (Begum N, Duddy N, Sandu OA, Reinzie J, and Ragolia L.
2093 11509551 In this study, we tested the hypothesis that insulin via the nitric oxide (NO)/cGMP pathway may inactivate Rho, resulting in a decrease in phosphorylation of the myosin-bound subunit (MBS(Thr695)) of MBP and in its activation.
2094 11509551 Treatment of confluent serum-starved VSMCs with insulin prevented thrombin-induced increases in membrane-associated RhoA, Rho kinase activation, and site-specific phosphorylation of MBS(Thr695) of MBP and caused MBP activation.
2095 11509551 Preexposure to N(G)-monomethyl-L-arginine, a NO synthase inhibitor, and R-p-8-(4-chlorophenylthio)cGMP, a cGMP antagonist, attenuated insulin's inhibitory effect on Rho translocation and restored thrombin-mediated Rho kinase activation and site-specific MBS(Thr695) phosphorylation, resulting in MBP inactivation.
2096 11509551 In contrast, 8-bromo-cGMP, a cGMP agonist, mimicked insulin's inhibitory effects by abolishing thrombin-mediated Rho signaling and promoted dephosphorylation of MBS(Thr695).
2097 11509551 Collectively, these results indicate that insulin inhibits Rho signaling by decreasing RhoA translocation via the NO/cGMP signaling pathway to cause MBP activation via site-specific dephosphorylation of its regulatory subunit MBS.
2098 11457835 However, treating cells with insulin increased the ability of nuclear extracts to enhance Sp1 binding.
2099 11457835 These findings indicate that the presence of the AT-rich element is essential for the actions of Sp1 in vitro and in vivo, and the combination of both spacing requirements and insulin responsiveness suggests that IRBP may interact directly with Sp1.
2100 11457862 Insulin down-regulated AQPap mRNA in 3T3-L1 adipocytes.
2101 11457862 Deletion and single base pair substitution analysis of the promoter revealed that these sequences were required for insulin-mediated repression of AQPap gene transcription.
2102 11463795 Insulin controls glucose uptake by translocating GLUT4 and other glucose transporters to the plasma membrane in muscle and adipose tissues by a mechanism that appears to require protein kinase C (PKC)-zeta/lambda operating downstream of phosphatidylinositol 3-kinase.
2103 11526109 Mutations of phosphoinositide-binding sites in both the pleckstrin homology and phosphotyrosine-binding domains significantly reduced the ability of Myc-tagged IRS-1 to translocate to the plasma membrane following insulin stimulation.
2104 11560925 Analysis of vessels from insulin resistant or diabetic animals indicates that CREB content is decreased in the vascular stroma.
2105 11560942 Exposure of R28 cells, a model of retinal neurons, to 20 mm glucose for 24 h attenuated the ability of 10 nm insulin to rescue them from serum deprivation-induced apoptosis and to phosphorylate Akt compared with 5 mm glucose.
2106 11560942 Azaserine, a glutamine:fructose-6-phosphate amidotransferase inhibitor, reversed the effect of 20 mm glucose, but not that of 1.5 mm glucosamine, on attenuation of the ability of insulin to promote cell survival and phosphorylate Akt as well as accumulation of UDP-HexNAc.
2107 11560942 These results suggest that the excessive glucose flux through the HBP may direct retinal neurons to undergo apoptosis in a bimodal fashion; i.e. via perturbation of the neuroprotective effect of insulin mediated by Akt and via induction of apoptosis possibly by altered glycosylation of proteins.
2108 11571295 Insulin and Alb-AGE stimulate VEGF mRNA and protein expression in retinal epithelial cells (ARPE-19).
2109 11598104 These results demonstrate the existence of an interaction between AMPK and early insulin signaling that could be of importance to our understanding of the potentiating effects of exercise on insulin signaling.
2110 11598137 PPARgamma ligands troglitazone (TRO, 10 microm) and rosiglitazone (RSG, 10 microm) attenuated the induction of p21(Cip1) protein by platelet-derived growth factor (PDGF) and insulin without affecting cognate mRNA levels in rat aortic smooth muscle cells (RASMC).
2111 11598137 TRO, RSG, and rottlerin inhibited PDGF-induced expression of p21(Cip1), but they did not affect insulin-induced expression of p21(Cip1).
2112 11711055 However, the effect of angiotensin II type-1 (AT(1)) receptor antagonists on insulin resistance is still controversial.
2113 11712406 Therefore, the agonistic activity of pioglitazone on PPAR-gamma may be involved in the mechanism for reducing insulin resistance.
2114 11712415 Moderate reduction of PPAR gamma activity by PPAR gamma/RXR inhibitors decreases TG content of WAT/muscle/liver due to increased leptin and increase in fatty-acid combustion and decrease in lipogenesis, thereby ameliorating HF diet-induced obesity and insulin resistance.
2115 11712415 Moreover, PPAR gamma/RXR inhibitors decrease lipogenesis in WAT, while TZD stimulate adipocyte differentiation and apoptosis, thereby both preventing adipocyte hypertrophy, which is associated with alleviation of insulin resistance presumably due to decreases in FFA, and TNF alpha, and upregulation of adiponectin.
2116 11712415 We conclude that although by different mechanisms, both PPAR gamma/RXR inhibitors and PPAR gamma agonist improve insulin resistance, which is associated with decreased TG content of muscle/liver and prevention of adipocyte hypertrophy.
2117 11793016 Substantial evidence suggests an important role for the expression of GLUT4 in adipocytes, in the pathogenesis of insulin resistance and Type II (non-insulin-dependent) diabetes mellitus.
2118 11793021 In all experimental models, clusterin was expressed in alpha cells in close correlation with islet cell proliferation, higher transcription of insulin mRNA and MAPKs activation.
2119 11795290 After initiating insulin, CETP increases without accompanying atherogenic changes in lipid metabolism.
2120 11795485 The role of leptin in the control of obesity, insulin resistance and type II diabetes has been reported, however, the regulatory mechanism of leptin in animals affected by hormones is not clearly understood.
2121 11795485 In this study, the effects of insulin, epinephrine, growth hormone or dexamethasone on the expression of leptin was examined in mouse primary adipocytes.
2122 11795485 The leptin expression was also studied in the adipose tissue of the mouse treated with insulin or growth hormone (0.3 or 0.6 units/animal).
2123 11795485 Insulin (100 nM) or dexamethasone (100 nM) stimulated leptin mRNA transcription while epinephrine (100 nM) alleviated its transcription in mouse primary adipocytes.
2124 11795485 These results indicate that both insulin and dexamethasone stimulate leptin gene expression and secretion of its product, whereas, growth hormone has no effect on the expression of leptin gene in mouse adipocytes.
2125 11806463 GLP-1 (glucagon-like peptide 1), proposed as a possible tool for Type 2 diabetes therapy, has insulin-like effects upon glucose metabolism in extrapancreatic tissues, whose plasma membranes contain specific receptors for the peptide, being those, at least in liver and muscle, not associated to the adenylate cyclase/cAMP system.
2126 11806463 GLP-1, as insulin, modulates the content of glycosylphosphatidylinositols (GPIs)--precursors of inositolphosphoglycans (IPGs), considered mediators of insulin action--in several extrapancreatic cell lines and in normal rat hepatocytes and adipocytes.
2127 11806463 In the present paper, we document that in a streptozotocin-induced Type 2 diabetic rat model, GLP-1, as insulin, provokes a rapid decrease of the [myo-3H-inositol]GPI content in isolated adipocytes--indicative of its hydrolysis and immediate short-lived generation of IPG--as that previously observed in normal animals; in hepatocytes, GLP-1, but not insulin, induced a reduction in the cellular GPI, although delayed in relation to normal rats.
2128 11806463 In adipocytes from streptozotocin-induced Type 1 diabetic rats, GLP-1, as insulin, seems to induce a reduction in the cellular GPI content, which was smaller and occurred later than that provoked in the Type 2 diabetic model; in the hepatocytes, GLP-1 and insulin failed to affect the control GPI content at any time tested.
2129 11817710 Serum insulin levels decreased with weight loss similar in magnitude to that noted for leptin; however, the insulin changes occurred more rapidly.
2130 11833461 In the liver, when the diet is rich in carbohydrates, insulin is secreted and stimulates the expression of genes involved in glucose utilization (glucokinase, L-pyruvate kinase, lipogenic enzymes) and inhibits genes involved in glucose production (phosphenolpyruvate carboxykinase).
2131 11842281 In advanced-stage CP, ductal cells were still strongly positive for COX-2, yet islets displayed a variable COX-2 staining pattern which was associated with the distribution of insulin-positive cells and with the clinical diabetes mellitus status of the patient.
2132 11880925 In conclusion, Leu-Enk stimulates insulin and glucagon secretion from the pancreas of normal rat through the cholinergic, alpha-2 adrenergic and opioid receptor pathways.
2133 11887931 Each ester augmented plasma insulin concentration and potentiated and/or prolonged the insulinotropic action of glucagon-like peptide 1 (GLP-1) injected intravenously (5 pmol/g of body wt) at min 5 of the test.
2134 11895220 This study examined overnight VLDL apoB metabolism and VLDL composition in six lean patients with type 1 diabetes during euglycaemia (controlled by a varying insulin infusion) and in six age-, sex- and BMI-matched control subjects.
2135 11895220 Total IGF-I concentrations were similar between the two groups; however, the GH area under the curve and free insulin concentrations were increased in patients with type 1 diabetes (GH: diabetes: 94.8 +/- 15.1 vs. controls: 45.6 +/- 10-6, mU/L/h, P < 0.04; free insulin: diabetes: 78.4 +/- 5.0 vs. controls: 28.3 +/- 3.26, pmol/l, P < 0.001).
2136 11903420 The effect of the angiotensin II receptor antagonist losartan on renal haemodynamics and insulin-mediated glucose disposal was examined in normotensive, normoalbuminuric type 1 diabetic patients using a double-blind, placebo-controlled, cross-over design.
2137 11606564 One serine residue located near the phosphotyrosine-binding (PTB) domain in IRS-1 (Ser(307) in rat IRS-1 or Ser(312) in human IRS-1) is phosphorylated via several mechanisms, including insulin-stimulated kinases or stress-activated kinases like JNK1.
2138 11606564 These results suggest that inhibition of PTB domain function in IRS-1 by phosphorylation of Ser(307) (Ser(312) in human IRS-1) might be a general mechanism to regulate insulin signaling.
2139 11707433 Inhibition of phosphatidylinositol 3-kinase with wortmannin blocked the ability of insulin to stimulate increased expression of endothelial nitric-oxide synthase, did not affect insulin-induced activation of MAP kinase, and increased the effects of insulin on prenylation of Ras and Rho proteins.
2140 11739083 Insulin-like growth factor-binding protein (IGFBP)-3 contains a highly basic COOH-terminal heparin-binding region, the P3 region, which is thought to be important in the binding of IGFBP-3 to endothelial cells.
2141 11739095 There was also no change in insulin-stimulated protein kinase B activity (1.3 +/- 0.1 vs. 1.4 +/- 0.2-fold stimulation with insulin) with training.
2142 11739098 After insulin injection, pY of the IR was not different between groups, whereas pY of IRS-1 and IRS-2 was reduced (P < 0.05) in HSD vs.
2143 11707432 We have found that insulin resistance induced by tumor necrosis factor-alpha (TNF-alpha) in 3T3-L1 adipocytes was accompanied by increased GM3 ganglioside expression caused by elevating GM3 synthase activity and its mRNA.
2144 11714718 The expression of the basic helix-loop-helix transcription factor c-Myc is induced in pancreatic islets of several different diabetic model animals and is possibly involved in suppression of the insulin gene transcription.
2145 11714718 Finally, adenovirus-mediated overexpression of WT PKC beta2, but not of other PKC isoforms, leads to suppression of the insulin gene transcription in pancreatic islets.
2146 11739394 Recent studies from our laboratory have shown that insulin stimulates myosin-bound phosphatase (MBP) in vascular smooth muscle cells (VSMCs) by decreasing site-specific phosphorylation of the myosin-bound subunit (MBS) of MBP via nitric oxide/cGMP-mediated Rho/Rho kinase inactivation.
2147 11739394 Hypertension (in spontaneous hypertensive rats) or expression of an active RhoA(V14) up-regulates Rho kinase activity and increases ROK-alpha/IRS-1 association resulting in IRS-1 serine phosphorylation that leads to inhibition of both insulin-induced IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activation.
2148 11739394 In contrast, expression of dominant negative RhoA or cGMP-dependent protein kinase type I alpha inactivates Rho kinase, abolishes ROK-alpha/IRS-1 association, and potentiates insulin-induced tyrosine phosphorylation and PI3-kinase activation leading to decreased MBS(T695) phosphorylation and decreased MBP inhibition.
2149 11751846 We examined the subcellular distribution of Munc18-c in response to acute (15-min) insulin (100 nm) stimulation after preincubation in 5 or 25 mm glucose +/- 0.6 nm insulin.
2150 11751846 Under each condition except high glucose + insulin preincubation, acute insulin increased Munc18-c (50-200%) in TS-PM and decreased Munc18-c (60%) in TI-LDM.
2151 11809189 Resistin, an adipocyte-derived cytokine, causes insulin resistance and glucose intolerance in mice.
2152 11812733 The decreased level of insulin is likely responsible for the increase in PDK2 mRNA level in starvation and diabetes.
2153 11812737 RIP-Delta(gamma)R islets are resistant to IL-1 + IFN-gamma-induced inhibition of insulin secretion and DNA damage, indicating that beta-cell IFN-gamma responsiveness is required for IL-1 + IFN-gamma-mediated beta-cell damage.
2154 11812737 In contrast, IL-1 + IFN-gamma fail to stimulate iNOS expression by insulin-expressing cells in islets isolated from RIP-DeltagammaR mice.
2155 11812750 In conclusion, the long-acting GLP-1 derivative NN2211 effectively reduces fasting as well as meal-related (approximately 12 h postadministration) glycemia by modifying insulin secretion, delaying gastric emptying, and suppressing prandial glucagon secretion.
2156 11812753 Insulin-stimulated Akt activity also increased after troglitazone treatment (from 32 +/- 8 to 107 +/- 32% stimulation, P < 0.05) but was unchanged after metformin therapy.
2157 11812758 In wild-type (WT) mice, insulin increased IRS-2 tyrosine phosphorylation (approximately 2.5-fold) and IRS-2-associated PI 3-kinase activity (approximately 3-fold).
2158 11812758 In conclusion, IRS-2 tyrosine phosphorylation and associated PI 3-kinase activity are markedly enhanced by insulin in the immediate period after exercise.
2159 11812758 IRS-2 signaling can partially account for the increase in insulin-stimulated phosphotyrosine-associated PI 3-kinase activity after exercise.
2160 11782469 Herein we observe that expression of increased levels of beta(2)-adrenergic receptor increasingly inhibits insulin-stimulated phosphorylation of its primary downstream substrates (IRS-1,2).
2161 11782469 Upon phosphorylation, the C-terminal cytoplasmic domain of the beta(2)-adrenergic receptor demonstrates a potent inhibitory feedback action that can block both insulin-stimulated autophosphorylation of the insulin receptor and phosphorylation of IRS-1,2 in NIH mouse 3T3-L1 adipocyte membranes.
2162 11781323 These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets.
2163 11799123 In gel-shift assays c-Myc bound to the E-box in the insulin gene promoter region.
2164 11799123 Furthermore, in betaTC1, MIN6, and HIT-T15 cells and primary rat islets, wild type insulin gene promoter activity was dramatically decreased by c-Myc overexpression, whereas the activity of an E-box mutated insulin promoter was not affected.
2165 11799123 In HeLa and HepG2 cells c-Myc exerted a suppressive effect on the insulin promoter activity only in the presence of NeuroD/BETA2 but not PDX-1.
2166 11799123 Both c-Myc and NeuroD can bind the E-box element in the insulin promoter, but unlike NeuroD, the c-Myc transactivation domain lacked the ability to activate insulin gene expression.
2167 11799123 In conclusion, increased expression of c-Myc in beta-cells suppresses the insulin gene transcription by inhibiting NeuroD-mediated transcriptional activation.
2168 11877384 The ability of LG100754 to both increase PPARgamma sensitivity and relieve insulin resistance implies that a deficiency in endogenous PPARgamma ligands may represent an early step in the development of insulin resistance.
2169 11904148 Leptin effects on insulin release were also measured.
2170 11904148 Leptin decreased UCP-2 expression by up to 75%, and maximally inhibited insulin release by 47%, at 22 mmol/l glucose.
2171 11904435 In mice, a heterozygous mutation in Pdx-1 alone, but not Hnf-1alpha(+/-), Hnf-3beta(+/-), or Hnf-4alpha(+/-), causes impaired glucose-stimulated insulin secretion in mice.
2172 11904435 The loss in beta-cell function in Pdx-1(+/-)/Hnf-3beta(+/-) mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-1(+/-)/Hnf-1alpha(+/-) mice.
2173 11906472 In particular, I(to) density is significantly increased in diabetic rat isolated ventricular myocytes treated in vitro with insulin or agents that activate pyruvate dehydrogenase.
2174 11907416 TNF-alpha and the combination of the three human cytokines caused a transient increase in cumulative insulin levels.
2175 11907416 TNF-alpha alone enhanced insulin content on day 3.
2176 11908465 Insulin treatment prevented the reduction in kinase activities, NR2B expression levels, CaMKII-NMDA receptor association and NMDA currents.
2177 11910345 However, at NID, there was a 40%-55% improvement (P = 0.05-0.0001) of both fasting and glucose-stimulated plasma insulin concentrations, and near-normalization of serum alanine aminotransferase activity (from 61 +/- 5 to 32 +/- 2 IU/L; P < 0.001).
2178 11911852 Thus, the comparative effects of exendin-4 and GLP-1 on insulin-stimulated 2-[3H]deoxyglucose (2-DOG) uptake were measured in fully differentiated L6 myotubes and 3T3-adipocytes, including co-incubation with inhibitors of the PI-3-kinase (wortmannin) and mitogen-activated protein (MAP) kinase (PD098059) pathways.
2179 11911852 In L6 myotubes, there was a concentration-dependent and PI-3-kinase-dependent increase in insulin-stimulated 2-DOG uptake with exendin-4 and GLP-1, e.g. for exendin-4 the C(I-200) value (concentration of insulin required to increase 2-DOG uptake 2-fold) decreased from 1.3 +/- 1.4 x 10(-7)M (insulin alone, n=16) to 5.9 +/- 1.3 x 10(-8)M (insulin+exendin-4 0.1nM, n=18, P<0.03).
2180 11912546 ACP1 is an enzyme involved in signal transduction of T-cell receptors, insulin, and other growth factor receptors.
2181 11912555 We measured PC-1 levels in these muscle samples to determine whether PC-1 content is elevated in this primate model of insulin resistance.
2182 11912559 We have recently demonstrated that insulin also inhibits the expression of intracellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), 2 major proinflammatory mediators, by human aortic endothelial cells (HAEC) and the proinflammatory mediator, nuclear factor (NF-kappa B), in the nucleus in parallel with an increase in endothelial nitric oxide synthase (e-NOS) expression.
2183 11914736 Their DNA binding activity and their transactivating potency can be modified in response to nutrients (glucose, NEFA) or hormonal stimuli (insulin, leptin, glucagon like peptide-1, growth hormone, prolactin) through kinase-dependent signalling pathways (PI3-K, p38MAPK, PKA, CaMK) modulating their affinities for DNA and/or for each other.
2184 11916909 Phosphorylation of 4E-BP1 and S6K1 was increased in diabetic rats infused with insulin in a dose-dependent manner, and the response was enhanced by leucine.
2185 11916909 The insulin-dependent mechanism is associated with increased phosphorylation of 4E-BP1 and S6K1.
2186 11916914 Transforming growth factor (TGF)-alpha- and epidermal growth factor (EGF)-induced signal transduction was directly compared with that of glucose and insulin-like growth factor-1 (IGF-1) in INS-1 cells.
2187 11916920 Increased fat mass, abdominal adiposity, and insulin resistance are typical findings in aging mammals and are frequently associated with leptin resistance and increased plasma leptin levels.
2188 11916922 Signaling through the phosphatidylinositol 3'-kinase (PI3K) pathway is crucial for metabolic responses to insulin, and defects in PI3K signaling have been demonstrated in type 2 diabetes.
2189 11916922 PTEN (MMAC1) is a lipid/protein phosphatase that can negatively regulate the PI3K pathway by dephosphorylating phosphatidylinositol (3,4,5)-triphosphate, but it is unclear whether PTEN is physiologically relevant to insulin signaling in vivo.
2190 11916922 Transfection of cells in culture with ASO targeting PTEN reduced PTEN mRNA and protein levels and increased insulin-stimulated Akt phosphorylation in alpha-mouse liver-12 (AML12) cells.
2191 11916922 Inhibition of PTEN expression also dramatically reduced insulin concentrations in ob/ob mice, improved the performance of db/db mice during insulin tolerance tests, and increased Akt phosphorylation in liver in response to insulin.
2192 11916922 These results suggest that PTEN plays a significant role in regulating glucose metabolism in vivo by negatively regulating insulin signaling.
2193 11916923 Exposure of isolated human adipocytes to insulin enhanced SREBP1 gene expression and promoted its proteolytic cleavage to the active form.
2194 11916923 Exposure of isolated human adipocytes to tumor necrosis factor-alpha (TNF-alpha) produced a marked and specific decrease in the mRNA encoding the SREBP1c isoform and completely blocked the insulin-induced cleavage of SREBP1 protein.
2195 11916925 This insulin resistance was associated with impaired insulin receptor substrate (IRS)-2-associated phosphatidylinositol 3' (PI3) kinase activation and IRS-2 tyrosine phosphorylation as well as significantly decreased protein kinase C (PKC)-zeta/lambda activation in response to insulin.
2196 11916933 At 12 months of age, obese rat hearts were insulin resistant with decreased GLUT4 protein expression.
2197 11919153 Centrally administered leptin did not affect peripheral insulin levels.
2198 11922615 However, in contrast to insulin, shikonin-stimulated glucose uptake was not strongly inhibited by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K).
2199 11926785 When the goal of insulin therapy in type 1 diabetes mellitus is near-normoglycemia, splitting the evening insulin treatment regimen into short-acting insulin at dinner and NPH insulin at bedtime reduces the risks for nocturnal hypoglycemia and hypoglycemia unawareness and decreases the hemoglobin A1c value compared with mixing short-acting insulin and NPH insulin at dinner.
2200 11928538 Some gene polymorphisms of TNF-alpha and IL-6 (associated with a different TNF-alpha or IL-6 transcription rate) and the plasma concentrations of the soluble TNF-alpha receptor are found to be simultaneously associated with resistance to insulin, the proportion of body fat and with the mortality linked with different chronic infections.
2201 11931352 Lack of modulation by short-term fasting and some other ingestive peptides that may interact with GLP-1, including leptin, glucagon, insulin, neuropeptide Y, and melanin-concentrating hormone. 4.
2202 11934674 Diabetic animals exhibited insulin resistance, whereas intracerebroventricular leptin significantly enhanced insulin sensitivity, as indicated by decreased SSPG.
2203 11934682 IGF-I therapy changes fasting triglyceride concentrations and VLDL composition probably because of an increase in insulin sensitivity.
2204 11935152 The E-selectin but not the ICAM-1 and VCAM-1 plasma concentrations correlated with the fasting insulin concentrations ( r = 0.62, p < 0.05) or the whole body glucose uptake ( r = 0.59, p < 0.05) in the clamp.
2205 11935160 We aimed to study the influence of Calpain 10 polymorphism on insulin action in fat cells.
2206 11923875 These mice show normal growth and development of beta-cells, but have reduced expression of Slc2a2 (also known as Glut2) and Gck (encoding glucokinase) in beta-cells, which results in defective glucose-stimulated insulin secretion and impaired glucose tolerance.
2207 11947963 Our results suggest that troglitazone may exert beneficial effects on insulin resistance by increasing the expression of GLUT4 in adipose tissue.
2208 11947965 We studied the preheparin serum lipoprotein lipase mass levels (prehaparin LPL mass) in type 2 diabetes mellitus patients and the effect of insulin therapy on the levels of preheparin LPL mass.
2209 11952162 Diabetes, vanadium, and insulin in vivo treatment did not affect muscle GSK-3beta activity as compared to controls.
2210 11958524 The cerebral occludin content in diabetic rats (115.4 +/- 18.6 arbitrary units) was significantly reduced compared to insulin-treated diabetic rats (649.1 +/- 141.2) or control rats (552.9 +/- 82.9), p < 0.001.
2211 11959983 PUGNAc treatment increased levels of O-GlcNAc and caused insulin resistance in 3T3-L1 adipocytes.
2212 11959983 These results suggest that elevation of O-GlcNAc levels attenuate insulin signaling and contribute to the mechanism by which increased flux through the HSP leads to insulin resistance in adipocytes.
2213 11960604 Thiazolidinediones are a novel class of antidiabetic drugs that reduce insulin resistance through interaction with nuclear peroxisome proliferator-activated receptor (PPAR)gamma.
2214 11961490 To investigate the effect of endogenous somatostatin on the interaction between endogenous insulin and exogenous cholecystokinin (CCK) in exocrine secretion of the totally isolated, perfused rat pancreas.
2215 11961490 Exogenous insulin (100 nM) also enhanced CCK-stimulated secretions in the streptozotocin-treated pancreas, which was also markedly increased by the somatostatin antagonist.
2216 11961490 Endogenous somatostatin inhibits the interaction of endogenous insulin and CCK on pancreatic exocrine secretion in the rat rather than reducing the action of CCK alone or endogenous release of insulin.
2217 11961501 GLP-1 also reduces plasma glucose levels by suppressing glucagon secretion from pancreatic a-cells and potentially by improving insulin sensitivity in peripheral tissues.
2218 11970897 Using subcellular membrane fractionation and immunofluorescence microscopy, we demonstrate that, in adipocytes, insulin induces plasma membrane translocation of FATPs from an intracellular perinuclear compartment to the plasma membrane.
2219 11970897 In contrast, treatment with TNF-alpha inhibited basal and insulin-induced LCFA uptake and reduced FATP1 and -4 levels.
2220 11976560 In this article we review the molecular mechanism by which insulin stimulates GLUT4 translocation in adipose cells, including the nature of the signaling pathways involved and the role of the cytoskeleton.
2221 11978627 Tumor necrosis factor-alpha (TNF-alpha) is a contributing cause of the insulin resistance seen in obesity and obesity-linked type 2 diabetes, but the mechanism(s) by which TNF-alpha induces insulin resistance is not understood.
2222 11978627 Nuclear factor-kappaB (NF-kappaB) was activated within 15 min of TNF-alpha addition. 3T3-L1 adipocytes expressing IkappaBalpha-DN, a nondegradable NF-kappaB inhibitor, exhibited normal morphology, global gene expression, and insulin responses.
2223 11978627 Thus the changes in adipocyte gene expression induced by TNF-alpha could lead to insulin resistance.
2224 11978634 Evidence from our laboratory and others has suggested that the IDDM2 locus determines diabetes susceptibility by modulating levels of insulin expression in the thymus: the diabetes-protective class III alleles at a repeat polymorphism upstream of the insulin gene are associated with higher levels than the predisposing class I.
2225 11978636 In fact, overexpression of both Pdx-1 and Isl-1 in IEC-6 cells (Isl-YK-12, -14, and -15 cells) gave them the ability to express insulin without exposure to betacellulin.
2226 11978642 Activation of VPAC1 has been implicated in elevating glucose output, whereas activation of VPAC2 may be involved in insulin secretion.
2227 11978642 A hypothesis that a VPAC2-selective agonist would enhance glucose disposal by stimulating insulin secretion without causing increased hepatic glucose production was tested using a novel selective agonist of VPAC2.
2228 11978647 In subcutaneous adipocytes, increasing insulin doses stimulated LPL expression, with maximal stimulation at 100 nmol/l insulin (control, 1.0 +/- 0.0 [mean +/- SE, protein expression relative to control]; 1 nmol/l insulin, 0.87 +/- 0.13; 100 nmol/l insulin, 1.68 +/- 0.19; P < 0.001).
2229 11978647 Insulin stimulated TNF-alpha secretion in a dose-dependent manner (P < 0.01); the addition of RSG (10(-8) mol/l) reduced TNF-alpha secretion (P < 0.05).
2230 11978647 In summary, chronic treatment of human adipocytes with insulin stimulates lipolysis and LPL protein expression.
2231 11978655 Our data suggest that alterations in ACC or AMPK activity in muscle do not contribute to the development of insulin resistance.
2232 11980629 Long-term DPPIV inhibition improves glucose tolerance in both normal and glucose-intolerant mice through improved islet function as judged by increased GLUT-2 expression, increased insulin secretion and protection from increased islet size in insulin resistance.
2233 11987032 By multivariate analyses, child leptin for the total study group was significantly associated with child body mass index (BMI) (R(2) = 0.65; p < 0.0001), child fasting insulin (R(2) = 0.08; p = 0.03), and female gender (R(2) = 0.28; p = 0.001).
2234 11989973 Insulin secretion was stimulated in islets treated with 5, 50, and 500 pmol/ L of IL-1beta for 2 h and 0.5 pmol/L for 6 h, respectively.
2235 11989973 These results suggested that the stimulatory effect of IL-1beta on the insulin secretion of rat islets is independent of iNOS-related NO production of IL-1beta and the enzyme activity of nitric oxide synthase.
2236 11991199 In this study, we attempted to determine whether insulin affects mitogenic signaling induced by platelet-derived growth factor (PDGF) in a rat VSMC cell line (A10 cells).
2237 11991199 However, the presence of insulin enhanced both DNA synthesis and MAPK activation by PDGF.
2238 11991199 We conclude that insulin, at pathophysiologically relevant concentrations, potentiates the PDGF-stimulated DNA synthesis, at least in part, by potentiating activation of the MAPK cascade.
2239 11991201 Therefore, PARP inhibitors prevent beta-cell necrosis, induce beta-cell replication and maintain insulin secretion.
2240 11809746 FAK co-immunoprecipitated with GSK-3beta, but only in cells overexpressing the KR (374 +/- 254 odu) and FAT (555 +/- 308) mutants was this association stimulated by insulin compared with NON (-209 +/- 92), CMV2 (-47 +/- 70), and WT (-39 +/- 31 odu).
2241 11809746 This suggests that FAK and GSK-3beta form both a constitutive association and a transient complex upon insulin stimulation, the dissociation of which requires normal function and localization of FAK.
2242 11809746 We conclude that FAK regulates the activity of Akt/protein kinase B and GSK-3beta and the association of GSK-3beta with FAK to influence insulin-stimulated glycogen synthesis in hepatocytes.
2243 11919188 These data suggested that a member of the Forkhead/winged helix family of transcription factors mediated the effect of insulin on PAI-1 transcription.
2244 11923308 In doubly mutant Lep(ob/ob) x Srebp-1(-/-) mice, fatty livers were markedly attenuated, but obesity and insulin resistance remained persistent.
2245 11964395 Conversely, GLUT2 and glucokinase mRNA levels were appropriately regulated by insulin, suggesting that insulin resistance is selective to gluconeogenic gene expression.
2246 11964395 Insulin-stimulated phosphorylation of the insulin receptor, insulin receptor substrate (IRS)-1, and associated phosphatidylinositol 3-kinase were normal in TG mice, whereas IRS-2 protein and phosphorylation were down-regulated compared with control mice.
2247 11964395 Furthermore, these results demonstrate that PEPCK overexpression results in a metabolic pattern that increases glucose-6-phosphatase mRNA and results in a selective decrease in IRS-2 protein, decreased phosphatidylinositol 3-kinase activity, and reduced ability of insulin to suppress gluconeogenic gene expression.
2248 11994285 Maturity onset diabetes of the young, subtype 1 (MODY1), is associated with defective glucose-dependent insulin secretion from pancreatic beta cells.
2249 11994285 Thus, in addition to the previously described indirect action of HNF4 alpha on insulin gene expression mediated through elevated HNF1 alpha levels, HNF4 alpha also activates the insulin gene directly, through a previously unrecognized cis element.
2250 12006586 Taken together, these data strongly suggest that unknown serine kinase activity and Ser(789) phosphorylation of IRS-1 may play an important role in attenuating insulin signaling in insulin-resistant animal models.
2251 12011047 In this study, subjecting rat islets to oxidative stress activates JNK, p38 MAPK, and protein kinase C, preceding the decrease of insulin gene expression.
2252 12011047 Adenovirus-mediated overexpression of dominant-negative type (DN) JNK, but not the p38 MAPK inhibitor SB203580 nor the protein kinase C inhibitor GF109203X, protected insulin gene expression and secretion from oxidative stress.
2253 12011047 These results were correlated with changes in the binding of the important transcription factor PDX-1 to the insulin promoter; adenoviral overexpression of DN-JNK preserved PDX-1 DNA binding activity in the face of oxidative stress, whereas wild type JNK overexpression decreased PDX-1 DNA binding activity.
2254 12011047 In conclusion, activation of JNK is involved in the reduction of insulin gene expression by oxidative stress, and suppression of the JNK pathway protects beta-cells from oxidative stress.
2255 12134168 We identified a cocrystal composition comprising 75% C8-HI and 25% human insulin that exhibits near-ideal basal pharmacodynamics in somatostatin-treated beagle dogs.
2256 12136128 Even modest overexpression of an isoform of O-GlcNAc transferase, in muscle and fat, leads to insulin resistance and hyperleptinemia.
2257 12137914 The mRNA expression of beta-actin was also slightly affected with time after ALX exposure, the proinsulin mRNA, however, remained unaffected as well as the pancreatic total insulin content.
2258 12137960 However, the physiological importance of GIP in the regulation of insulin secretion has been shown to even exceed that of GLP-1.
2259 12099888 In insulin deficiency, increased lipid delivery and oxidation suppress skeletal-muscle glucose oxidation by inhibiting pyruvate dehydrogenase complex (PDC) activity via enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4, which phosphorylates (and inactivates) PDC.
2260 12118006 EGCG also mimics insulin by increasing phosphoinositide 3-kinase, mitogen-activated protein kinase, and p70(s6k) activity.
2261 12138086 The ability of the growth factors epidermal growth factor (EGF), transforming growth factor alpha, and platelet-derived growth factor to exert insulin-like effects on glucose transport and lipolysis were examined in human and rat fat cells.
2262 12138086 No effects were found in rat fat cells, whereas EGF (EC(50) for glucose transport approximately 0.02 nm) and transforming growth factor alpha (EC(50) approximately 0.2 nm), but not platelet-derived growth factor, mimicked the effects of insulin (EC(50) approximately 0.2 nm) on both pathways.
2263 12138086 EGF mimics the effects of insulin on both the metabolic and mitogenic pathways but utilize in part different signaling pathways.
2264 12138086 Both insulin and EGF increase the tyrosine phosphorylation and activation of IRS-1 and IRS-2, whereas EGF is also capable of activating additional PI 3-kinase pools and, thus, can augment the downstream signaling of insulin in insulin-resistant states like Type 2 diabetes.
2265 12150711 Glucose-dependent insulinotropic polypeptide (GIP) is an important incretin hormone, which potentiates glucose-induced insulin secretion.
2266 12150711 This was associated with a significantly greater AUC for insulin (2.1-fold; P <0.001) for both analogues compared with native GIP.
2267 12198128 Studies in streptozotocin-induced diabetic rats have shown that CBS enzyme activity is elevated in the liver but not in the kidney, and this effect is reversed by insulin treatment.
2268 12198128 In H4IIE cells, a rat hepatoma cell culture model, glucocorticoids increased the cellular levels of CBS enzyme protein and CBS mRNA; insulin inhibited this stimulatory effect.
2269 12198128 Nuclear run-on experiments in the rat cells confirmed that stimulation of CBS gene expression by glucocorticoids and the inhibition by insulin occurred at the transcriptional level.
2270 12200416 However, in the presence of high glucose both insulin and leptin caused a significant increase in the activity of acyl-CoA: cholesterol O-acyltransferase (ACAT) combined with a significant reduction in the level of hormone-sensitive lipase (HSL).
2271 12200416 This contrasts with 3T3-L1 adipocytes, where HSL activity and expression are increased by insulin in high glucose conditions.
2272 12228220 We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two critical signaling molecules for insulin action, for ubiquitin-mediated degradation.
2273 12228220 Thus, SOCS-mediated degradation of IRS proteins, presumably via the elongin BC ubiquitin-ligase, might be a general mechanism of inflammation-induced insulin resistance, providing a target for therapy.
2274 12368292 Therefore, MafA is a beta-cell-specific and glucose-regulated transcriptional activator for insulin gene expression and thus may be involved in the function and development of beta-cells as well as in the pathogenesis of diabetes.
2275 12582462 Somatostatin analogues such as octreotide have shown promise as a safe and effective treatment for severe proliferative diabetic retinopathy by blocking the local and systemic production of growth hormone and insulin-like growth factor type 1 associated with angiogenesis and endothelial cell proliferation.
2276 12583603 Leptin production in the placenta is also increased in diabetic pregnancy with insulin treatment.
2277 12586550 HD transgenic mice develop an age-dependent reduction of insulin mRNA expression and diminished expression of key regulators of insulin gene transcription, including the pancreatic homeoprotein PDX-1, E2A proteins, and the coactivators CBP and p300.
2278 12608111 Amylin modulates insulin sensitivity of skeletal muscle, contributes to the regulation of blood pressure and causes vasodilatation.
2279 12626032 In conclusion, increased TNF-alpha and leptin levels may contribute to insulin resistance in GDM and in the third trimester of normal pregnancy and may negatively influence the anthropometric parameters of the newborns.
2280 12643137 Rare inactivating mutations of the gene encoding PPAR gamma are associated with insulin resistance type 2 diabetes, and hypertension, whereas a rare gain of function mutation causes extreme obesity.
2281 12643137 A common polymorphism (Pro12Ala) of the adipose tissue-specific gamma 2 isoform is associated with increased insulin sensitivity and decreased risk of developing type 2 diabetes.
2282 12643189 Improvement in glycemic control, insulin and insulin sensitizers, cholesterol lowering, hypolipidemic agents, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers have improved clinical cardiovascular outcomes and have also been shown to improve endothelial function.
2283 12660880 Resistin treatment impaired glucose tolerance and insulin action.
2284 12688387 The present study aimed to determine whether pharmacological treatment with gastrin and EGF can significantly stimulate beta-cell regeneration in chronic, severe insulin-dependent diabetes.
2285 12688631 We have generated a transgenic mouse expressing a chimaeric phogrin-enhanced green fluorescent protein (EGFP) targeted to pancreatic beta-cells by the rat insulin II promoter.
2286 12905770 In normal islets, insulin + cells accounted for (59.37 +/- 1.21)%, and some islet cells were observed expressing Fas.
2287 12356335 GLP-1 increased the amplitude of pulses and the magnitude of insulin secretion from the perifused islets, without affecting the average time interval between pulses.
2288 12388136 In the control group, adiponectin mRNA levels were negatively correlated with fasting insulin (P < 0.05) and positively correlated with insulin sensitivity (P < 0.05).
2289 12397027 Increased flux through the hexosamine biosynthesis pathway has been implicated in the development of glucose-induced insulin resistance and may promote the modification of certain proteins with O-linked N-acetylglucosamine (O-GlcNAc).
2290 12397027 As assessed by immunoblotting with an O-GlcNAc-specific antibody, high glucose and/or insulin enhanced O-GlcNAcylation of numerous proteins, including the transcription factor Sp1, a known substrate for this modification.
2291 12410639 In L6 myotubes treated for 24 h with insulin there was increased expression of the HK isoform, HKII, and increased glucose phosphorylation without a concomitant increase in glucose transport, indirectly suggesting that phosphorylation of glucose was a target of insulin action [Osawa, Printz, Whitesell and Granner (1995) Diabetes 44, 1426-1432].
2292 12417588 Insulin stimulation of JNK activity required phosphatidylinositol 3-kinase and Grb2 signaling.
2293 12417588 However, the direct binding of JNK to Irs1 was not required for its activation by insulin, whereas direct binding was required for Ser(307) phosphorylation of Irs1.
2294 12417588 Insulin-stimulated Ser(307) phosphorylation was reduced 80% in cells lacking JNK1 and JNK2 or in cells expressing a mutant Irs1 protein lacking the JNK binding site.
2295 12417588 These results support the hypothesis that JNK is a negative feedback regulator of insulin action by phosphorylating Ser(307) in Irs1.
2296 12431986 The adipocyte-derived hormone adiponectin has been shown to play important roles in the regulation of energy homeostasis and insulin sensitivity.
2297 12456686 Here, we identified a novel gene, termed diabetes-related ankyrin repeat protein (DARP) that is up-regulated in the heart of KKA(y) mouse, a type 2 diabetes and insulin resistance model animal.
2298 12456686 We confirmed that DARP expression is also altered in Zucker fatty rat, another insulin resistance model animal.
2299 12475913 Glucose-dependent insulinotropic polypeptide (GIP) is secreted postprandially and acts in concert with glucose to stimulate insulin secretion from the pancreas.
2300 12524232 Lipid peroxides serum levels were 18% lower (P<0.01), and serum paraoxonase activity was 30% higher (P<0.01) in mice supplemented with 1.0 U/mL insulin compared with controls.
2301 12524233 Although common insulin resistance is associated with several biochemical perturbations, including elevated C-reactive protein (CRP), the biochemical profile in subjects with mutant LMNA is incompletely defined.
2302 12510059 An additional mechanism for modulating insulin signaling is via the down-regulation of IRS-1 protein levels.
2303 12510059 Insulin-induced degradation of IRS-1 has been well documented, both in cells as well as in patients with diabetes.
2304 12510059 In the present study we have examined the potential role of different signaling cascades in the insulin-induced degradation of IRS-1.
2305 12510059 Second, knockout cells lacking one of the key effectors of this cascade, the phosphoinositide-dependent kinase-1, were found to be deficient in the insulin-stimulated degradation of IRS-1.
2306 12510059 Third, concurrent with the decrease in IRS-1 degradation, the inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin also blocked the insulin-stimulated increase in Ser(312) phosphorylation.
2307 12510059 Finally, an inhibitor of c-Jun N-terminal kinase, SP600125, at 10 microm did not block IRS-1 degradation and IRS-1 Ser(312) phosphorylation yet completely blocked insulin-stimulated c-Jun phosphorylation.
2308 12510059 In summary, our results indicate that the insulin-stimulated degradation of IRS-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the Ser(312) phosphorylation of IRS-1.
2309 12554784 TNFalpha, which activates three different MAPKs [ERK, p38, and jun amino terminal kinase (JNK)], also induces insulin resistance.
2310 12554784 In the context of our earlier report showing down-regulation of glucose transporter 4 by MEK1-ERK and MKK6/3-p38, the present findings suggest that chronic activation of ERK, p38, or JNK can induce insulin resistance by affecting glucose transporter expression and insulin signaling, though via distinctly different mechanisms.
2311 12475752 Improvement of insulin sensitivity and lipid and glucose metabolism by coactivation of both nuclear peroxisome proliferator-activated receptor (PPAR)gamma and PPARalpha potentially provides beneficial effects over existing PPARgamma and alpha preferential drugs, respectively, in treatment of type 2 diabetes.
2312 12496137 In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content.
2313 12510060 Thus, Rab3A plays an important in vivo role facilitating the efficiency of insulin exocytosis, most likely at the level of replenishing the ready releasable pool of beta-granules.
2314 12493745 Insulin-positive beta-cells were decreased to nearly zero in IRS-2(-/-) mice with diabetes.
2315 12540373 The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that act via the enteroinsular axis to potentiate insulin secretion from the pancreas in a glucose-dependent manner.
2316 12540373 Pancreatic insulin content and gene expression were reduced in GIPR(-/-) mice compared with GIPR(+/+) mice.
2317 12540373 In conclusion, GIPR(-/-) mice exhibit altered islet structure and topography and increased islet sensitivity to GLP-1 despite a decrease in pancreatic insulin content and gene expression.
2318 12540375 By use of subfractionation and Western blot analysis techniques, the CM/DP group demonstrated a higher skeletal muscle sarcolemma-associated (days 1 and 60) and white adipose tissue plasma membrane-associated (day 60) GLUT4 in the basal state with a lack of insulin-induced translocation.
2319 12540375 We conclude that the offspring of a diabetic mother with ad libitum postnatal nutrition demonstrates increased food intake and resistance to insulin-induced translocation of GLUT4 in skeletal muscle and white adipose tissue.
2320 12560330 We recently demonstrated that IL-6 inhibits insulin signaling in hepatocytes (Senn, J.
2321 12560330 Since several SOCS proteins are induced by IL-6, a working hypothesis is that IL-6-dependent insulin resistance is mediated, at least in part, by induction of SOCS protein(s) in insulin target cells.
2322 12560330 Ectopically expressed SOCS-3 associated with the IR and suppressed insulin-dependent receptor autophosphorylation, insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase, and activation of Akt.
2323 12634421 To establish whether IDE hypofunction decreases Abeta and insulin degradation in vivo and chronically increases their levels, we characterized mice with homozygous deletions of the IDE gene (IDE --).
2324 12634421 IDE deficiency resulted in a >50% decrease in Abeta degradation in both brain membrane fractions and primary neuronal cultures and a similar deficit in insulin degradation in liver.
2325 12634920 In previous studies of an Ala54Thr substitution in FABP2, the Thr-allele showed association with increased lipid oxidation, elevated plasma lipids, and impaired insulin sensitivity.
2326 12663464 Recent evidence has shown that activation of phosphatidyinositol-3-kinase (PI3K) and Akt, necessary for insulin stimulation of glucose transport, is impaired in insulin resistance.
2327 12663464 It is unknown, however, which Akt isoform shows impaired activation in insulin resistance.
2328 12663464 Hence, we investigated the stimulation of PI3K and Akt-1, -2, and -3 by insulin and epidermal growth factors (EGFs) in skeletal muscles from lean and obese insulin-resistant humans.
2329 12663464 Insulin activated all Akt isoforms in lean muscles, whereas only Akt-1 was activated in obese muscles.
2330 12670229 Inhibition of PTP1B is expected to improve insulin action, and the design of small molecule PTP1B inhibitors to treat type II diabetes has received considerable attention.
2331 12670740 For example, the thiazolidinediones, a class of oral anti-diabetic agents that reduce insulin resistance and improve beta-cell function, might mediate these effects by regulating adipocyte-derived factors, in particular TNF-alpha and FFAs.
2332 12671184 Mechanistically, insulin resistance has been associated with hyperinsulinemia, increased levels of growth factors including IGF-1, and alterations in NF-kappaB and peroxisome proliferator-activated receptor signaling, which may promote colon cancer through their effects on colonocyte kinetics.
2333 12672257 Ip(5)I and Ip(6)I antagonized Ap(5)A-mediated inhibition of insulin release. [(3)H]Thymidine incorporation into VSMC was not influenced by either synthetic diadenosine polyphosphate analogue, indicating that Ap(4)A does not act by itself in this case but (active) degradation products mediate the effect.
2334 12672257 The data indicate the following. (1) Since nondegradable compounds inhibit insulin release as well as Ap(4)A, it is Ap(4)A itself and not any of its degradation products that induces this effect. (2) Diadenosine polyphosphate effects on cell proliferation are mediated via a degradation product in contrast to their effect on insulin release. (3) Ip(5)I and Ip(6)I act like antagonists.
2335 12675668 The I27L polymorphism of TCF1 is an independent determinant of beta-cell function by affecting both 1st and 2nd phase insulin response.
2336 12676649 Plasma glucose, insulin, triglyceride, and nonesterified fatty acid levels were elevated in untreated db/db mice compared with untreated C57BL/6J mice, and these parameters were significantly ameliorated in the PPARgamma agonist-treated groups.
2337 12678487 In this review, we summarize the existing work that implicates the HSP and O-GlcNAc modification as nutrient sensors and regulators of insulin signaling.
2338 12678842 These observations strongly support PTP1B as a negative regulator of insulin action, thereby making it an ideal therapeutic target for intervention in type 2 diabetes and obesity.
2339 12678843 Recent studies have demonstrated that protein tyrosine phosphatase 1B (PTP1B) is involved in the down regulation of insulin signaling.
2340 12679424 As expected, in control cells transfected with wild-type IRS-1, insulin stimulation caused an increase in p85 coimmunoprecipitated with IRS-1 as well as a 10-fold increase in IRS-1-associated PI 3-kinase activity.
2341 12679424 Interestingly, when cells transfected with IRS1-T608R were stimulated with insulin, both the amount of p85 coimmunoprecipitated with IRS1-T608R as well as the associated PI 3-kinase activity were approximately 50% less than those observed with wild-type IRS-1.
2342 12679437 Across a spectrum of subjects with diabetes, impaired fasting glucose/mild diabetes, or BMI-matched nondiabetic controls, normalized leptin significantly correlated with glucose-induced insulin release, but not with insulin sensitivity.
2343 12682906 In subsequent binding studies, TZDs were demonstrated to enhance insulin action by activating peroxisome proliferator-activated receptor gamma (PPARgamma).
2344 12682906 PPARgamma is a member of the ligand-activated nuclear receptor superfamily that promotes adipogenesis and enhances insulin sensitivity by controlling the expression of genes in glucose and lipid metabolism.
2345 12683947 Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level.
2346 12684063 That the effects of Mad on insulin expression were mediated through PDX-1 was further substantiated by studies showing inhibition of insulin promoter activation by Mad in the presence of mutated PDX-1 binding site.
2347 12684063 Such regulation of insulin expression by Mad with modulation of PDX-1 expression and DNA binding activity could offer useful therapeutic and/or experimental tools to promote insulin production in appropriate cell types.
2348 12686458 Insulin and cyclic adenosine monophosphate (cAMP) generation induced by PACAP were investigated in islets isolated from the spontaneously diabetic Goto-Kakizaki (GK) rat.
2349 12686458 PACAP significantly potentiated glucose-stimulated insulin release in isolated islets of normal but not of GK rats.
2350 12686458 In conclusion, using improved immunocytochemistry techniques and electron microscopy (EM), PACAP was shown to be expressed both in normal and diabetic islet cells and localized to secretory granules of insulin and glucagon cells.
2351 12687334 Recently, serum GGT concentrations have been associated with many cardiovascular disease risk factors or components of the insulin resistance syndrome.
2352 12689528 Leptin levels were positively correlated with serum insulin and C-peptide levels.
2353 12691857 In stepwise multiple regression analysis serum TSA independently correlated with subject waist/hip ratio (r(2)=0.167, P<0.02) and diastolic blood pressure (r(2)=0.300, P<0.01) but not with age, BMI, serum insulin-like growth factor binding protein (IGFBP-1), fasting plasma glucose or systolic or diastolic blood pressure.
2354 12692007 In multivariable logistic regression, the fully adjusted odds ratio (OR) for elevated fasting insulin (>or=51.6 pmol/L) increased with tertile of BMI, CRP, and IL-6, such that the ORs in the highest versus lowest tertile of each parameter were 9.0 (95% confidence interval [CI], 4.4 to 18.7), 4.4 (95% CI, 1.9 to 10.1), and 2.0 (95% CI, 0.9 to 4.2), respectively.
2355 12692007 Furthermore, increasing levels of CRP were associated with a stepwise gradient in odds for elevated fasting insulin among both lean and overweight women.
2356 12589707 Using pharmacological and molecular strategies to regulate AMPK activity in rat islets and clonal MIN6 beta-cells, we show here that the effects of AMPK are exerted largely upstream of insulin release.
2357 12589707 These results indicate that inhibition of AMPK by glucose is essential for the activation of insulin secretion by the sugar, and may contribute to the transcriptional stimulation of the preproinsulin gene.
2358 12594228 A 24-h long insulin treatment desensitized the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) and p42/p44 MAPK pathways toward a second stimulation with insulin or insulin-like growth factor-1 and led to decreased insulin-induced glucose uptake.
2359 12594228 Co-treatment of cells with insulin and LY294002, while reducing total IRS-1 phosphorylation, increased its phosphotyrosine content, enhancing IRS-1/PI3K association.
2360 12594228 PDK1, mTOR, and MAPK inhibitors did not block insulin-induced reduction of IRS-1, suggesting that the PI3K serine-kinase activity causes IRS-1 serine phosphorylation and its commitment to proteasomal degradation.
2361 12594228 Suppression of IRS-1/2 down-regulation by LY294002 rescued the responsiveness of PKB and MAPK toward acute insulin stimulation.
2362 12594228 IRS-2 appears to be the chief molecule responsible for MAPK and PKB activation by insulin, as knockdown of IRS-2 (but not IRS-1) by RNA interference severely impaired activation of both kinases.
2363 12594228 In summary, (i) PI3K mediates insulin-induced reduction of IRS-1 by phosphorylating it while a PI3K/mTOR pathway controls insulin-induced reduction of IRS-2, (ii) in L6 cells, IRS-2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK, (iii) the mechanism of IRS-1/2 down-regulation is different in L6 cells compared with 3T3-L1 adipocytes.
2364 12626433 Consequently, diabetes may be worsened by enzymatic degradation of insulin by gelatinase B and by the consequent enhancement of the autoimmune process.
2365 12689920 Insulin or glucose, when added separately, increased egr-1 mRNA levels and promoter activity, as well as Egr-1 protein levels in nuclear extracts.
2366 12689920 When insulin was added to cells preincubated with glucose, the two had an additive effect on Egr-1 expression.
2367 12689920 Furthermore, vascular endothelial growth factor receptor-1 (flt-1) and plasminogen activator inhibitor-1, two known Egr-1-responsive genes, were also upregulated in the presence of insulin or glucose.
2368 12689920 An investigation into the underlying molecular mechanisms demonstrated that insulin, but not glucose, increased Egr-1 expression through extracellular signal-regulated kinase 1/2 activation, which is consistent with our previous reports.
2369 12689920 Differential regulation of Egr-1 expression by insulin and glucose in vascular cells may be one of the initial key events that plays a crucial role in the development of diabetic vascular complications.
2370 12697773 Second, this normalization occurred despite very low levels of liver glucokinase expression in the insulin-deficient STZ-injected rats.
2371 12712243 Transfection of wild-type HNF-1alpha increased the reporter activities of GLUT2 and insulin promoters in NIH3T3 and SK-Hep1 cells, while R263L mutant was defective in transactivation of those promoters.
2372 12714437 TNF-alpha, IL-6, and CRP were significantly correlated with insulin resistance estimated by the homeostatic model assessment (r=0.48, P<0.05; r=0.56, P<0.01; and r=0.35, P<0.05, respectively).
2373 12783165 The glucagonoma cell line InR1G9 was transduced with a Pdx1-encoding lentiviral vector and insulin and glucagon mRNA levels were analysed by northern blot and real-time PCR.
2374 12783165 In glucagonoma cells transduced with a Pdx1-encoding lentiviral vector, insulin gene expression was induced while glucagon mRNA levels were reduced by 50 to 60%.
2375 12808136 In addition, muscle mitochondrial protein synthesis, and COX and citrate synthase enzyme activities were increased by insulin (P < 0.05).
2376 12808880 Glucagon-like peptide-1 (GLP-1 (7-36) amide) is a gut hormone released from L-cells in the small intestine in response to the ingestion of nutrients and enhances the glucose-dependent secretion of insulin from pancreatic beta-cells.
2377 12814870 The protein hormone, resistin, secreted specifically by the adipose tissues, is found to antagonize insulin action upon glucose uptake and may serve as an important role between human obesity and insulin resistance.
2378 12815005 Circulating concentrations of insulin increase with dietary consumption of high glycemic index foods, which, in turn, may influence IGF-I levels or activity, but the relevance of such dietary patterns for breast cancer risk is unclear.
2379 12816347 PepT1-mediated transport is up-regulated by short-term exposure to receptor agonists such as EGF, insulin, leptin, and clonidine, and down-regulated by VIP.
2380 12818733 ACE inhibitor therapy reduces both microvascular and macrovascular complications in diabetes and appears to improve insulin sensitivity and glucose metabolism.
2381 12829623 The adipocyte secreted hormone resistin has been proposed as a link between the adipocyte and insulin resistance by inhibition of insulin-stimulated glucose uptake and/or blocking adipocyte differentiation.
2382 12829640 The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription.
2383 12829640 These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology.
2384 12829645 Taken together, these findings suggest that the reduction in circulating or intracellular lipids by activation of PPAR-alpha improved insulin sensitivity and the diabetic condition of MKR mice.
2385 12829646 Thus, adiponectin expression from adipose tissue is higher in lean subjects and women, and is associated with higher degrees of insulin sensitivity and lower TNF-alpha expression.
2386 12829648 In the central nervous system, insulin directly decreases hunger sensation but could also act indirectly by modulating ghrelin and leptin secretion.
2387 12829648 In type 2 diabetic patients without insulin treatment, ghrelin decreased by 18 +/- 7% (P < 0.05) only after 4 mU x kg(-1) x min(-1) insulin infusion and leptin increased by 19 +/- 6% (P < 0.05).
2388 12829648 In conclusion, insulin reduces plasma ghrelin in nondiabetic patients and, to a lesser extent, in type 2 diabetic patients before insulin therapy.
2389 12829649 After additional adjustment for BMI, waist-to-hip ratio, and fasting glucose and insulin, only the interleukin-6 association remained statistically significant (HR = 1.6, 1.01-2.7).
2390 12829653 The present study was designed to determine whether non-cross-linking advanced glycation end products (AGEs) on RyR2 increase with chronic diabetes and if formation of these post-translational complexes could be attenuated with insulin treatment.
2391 12724332 Insulin inhibition of Foxo1-(208-652)-stimulated transactivation is mediated by PI 3-kinase but in contrast to full-length Foxo1, does not require either of the two PKB/Akt phosphorylation sites (Ser253 and Ser316) present in the protein fragment.
2392 12730204 In response to insulin, NEU3 was found to undergo tyrosine phosphorylation and subsequent association with the Grb2 protein, thus being activated and causing negative regulation of insulin signaling.
2393 12730204 In fact, accumulation of GM1 and GM2, the possible sialidase products in transgenic tissues, caused inhibition of IR phosphorylation in vitro, and blocking of association with Grb2 resulted in reversion of impaired insulin signaling in L6 cells.
2394 12730204 The data indicate that NEU3 indeed participates in the control of insulin signaling, probably via modulation of gangliosides and interaction with Grb2, and that the mice can serve as a valuable model for human insulin-resistant diabetes.
2395 12732648 Our data suggest that inhibition of NF-kappaB activity is a mechanism by which PPAR-gamma agonists improve insulin sensitivity in vivo and that adipocyte NF-kappaB is a potential therapeutic target for obesity-linked type 2 diabetes.
2396 12734206 We report here that human melanoma M2 cells lacking FLNa expression exhibited normal insulin receptor (IR) signaling, whereas FLNa-expressing A7 cells were unable to elicit insulin-dependent Shc tyrosine phosphorylation and p42/44 MAPK activation despite no significant defect in IR-stimulated phosphorylation of insulin receptor substrate-1 or activation of the phosphatidylinositol 3-kinase/AKT cascade.
2397 12734206 Insulin-dependent translocation of Shc, SOS1, and MAPK to lipid raft microdomains was markedly attenuated by FLNa expression.
2398 12734206 Coimmunoprecipitation experiments and in vitro binding assays demonstrated that FLNa binds constitutively to IR and that neither insulin nor depolymerization of actin by cytochalasin D affected this interaction.
2399 12734206 Ectopic expression of a C-terminal fragment of FLNa (FLNaCT) in HepG2 cells blocked the endogenous IR-FLNa interaction and potentiated insulin-stimulated MAPK phosphorylation and transactivation of Elk-1 compared with vector-transfected cells.
2400 12775712 The effects of insulin on vascular endothelial growth factor (VEGF) expression in cultured vascular cells and in angiogenesis were characterized.
2401 12775712 Insulin increased VEGF mRNA levels in mouse aortic smooth muscle cells from 10(-9) to 10(-7) m with an initial peak of 3.7-fold increases at 1 h and a second peak of 2.8-fold after 12 h.
2402 12775712 In contrast, the chronic effect of insulin on VEGF expression was partially inhibited by both LY294002 or PD98059 as well as by the overexpression of dominant negatives of PI 3-kinase or Ras.
2403 12775712 Thus, unlike other cells, insulin can regulate VEGF expression by both IRS-1/PI 3-kinase-Akt cascade and Ras-MAPK pathways in aortic smooth muscle cells.
2404 12775712 The in vivo results provide direct evidence that insulin can modulate hypoxia-induced angiogenesis via reduction in VEGF expression in vivo.
2405 12805374 In AZIP mice, ablation of liver PPAR gamma reduced the hepatic steatosis but worsened the hyperlipidemia, triglyceride clearance, and muscle insulin resistance.
2406 12805374 Interestingly, mice without liver PPAR gamma, but with adipose tissue, developed relative fat intolerance, increased adiposity, hyperlipidemia, and insulin resistance.
2407 12898215 We conclude that alterations of MGST3 are unlikely to contribute to T2DM or differences in insulin sensitivity in the Pima Indians.
2408 12917066 To present a case of a young woman with new-onset diabetes mellitus resistant to insulin attributable to Cushing's syndrome caused by ectopic production of corticotropin by a metastatic gastrinoma.
2409 12917066 The patient required large doses of insulin to control plasma glucose, and further work-up confirmed the presence of Cushing's syndrome caused by ectopic production of corticotropin from a metastatic gastrinoma.
2410 12920661 This study set out to define relationships between changes in plasma leptin and changes in body weight, plasma insulin and blood glucose control during a 12-month crossover study of once-daily Ultratard or twice-daily Insulatard insulin.
2411 12923570 Glucagon-like peptide 1 (GLP-1) is released from neuroendocrine cells in the intestine in the postprandial state and augments glucose-stimulated insulin secretion from pancreatic beta cells.
2412 12924619 The results suggest that the Chinese medicine JTKL, which contains PG as one of its valid components, improves insulin resistance by modulating muscle fiber composition and TNF-alpha in skeletal muscles in hypertensive and insulin-resistant FFR.
2413 12925701 Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by thiazolidinediones (TZDs) improves insulin resistance by increasing insulin-stimulated glucose disposal in skeletal muscle.
2414 12935319 The results show that glucose level and glycosylated hemoglobin were increased and plasma insulin and liver glycogen were decreased in diabetic rats, and that treatment with AMFEt reversed the effects of diabetes on these biochemical parameters to near-normal levels.
2415 12940867 The aim of this study was to investigate the effect of insulin and an insulin-sensitizing agent, rosiglitazone (RSG), on the production of plasminogen-activator inhibitor-1 (PAI-1) in isolated subcutaneous abdominal adipocytes.
2416 12940867 In contrast, insulin + RSG (10-8 m) reduced PAI-1 production relative to insulin alone (***p < 0.001), whilst RSG alone reduced PAI-1 protein secretion in a concentration-dependent manner (RSG at 10-10 m: 50.4 +/- 2.87 ng/ml downward arrow ***; RSG at 10-5 m: 30.3 +/- 2.0 ng/ml downward arrow ***; p < 0.001).
2417 12940867 Insulin stimulated PAI-1 secretion, whilst RSG reduced both PAI-1 secretion alone and in combination with insulin.
2418 12941435 In mice treated with streptozotocin, which depletes insulin, 5-HTP did not increase serum leptin levels.
2419 12941722 GLP-1 stimulates insulin secretion and inhibits glucagon secretion.
2420 12941722 We have previously shown that GLP-1 does not cause hypoglycemia in obese type 2 diabetic patients with insulin resistance amounting to 5.4 +/- 1.1 according to homeostasis model assessment (HOMA).
2421 12941761 In contrast, HMR 1964 produced a marginal activation of the Shc/ERK kinase cascade and was equipotent to insulin in stimulating DNA synthesis in myoblasts.
2422 12941762 The lack of IRS-2 did not result in enhanced IRS-1 tyrosine phosphorylation or IRS-1-associated phosphatidylinositol (PI) 3-kinase activity on insulin stimulation.
2423 12941762 Total insulin-induced PI 3-kinase activity was decreased by 50% in IRS-2(-/-) hepatocytes, but the translocation of PI-3,4,5-trisphosphate to the plasma membrane in these cells was almost completely abolished.
2424 12941762 Downstream PI 3-kinase, activation of Akt, glycogen synthase kinase (GSK)-3 (alpha and beta isoforms), Foxo1, and atypical protein kinase C were blunted in insulin-stimulated IRS-2(-/-) cells.
2425 12941762 Reconstitution of IRS-2(-/-) hepatocytes with adenoviral IRS-2 restored activation of these pathways, demonstrating that IRS-2 is essential for functional insulin signaling in hepatocytes.
2426 12941762 However, insulin was not able to suppress gluconeogenic gene expression in primary hepatocytes lacking IRS-2, but when IRS-2 signaling was reconstituted, these cells recovered this response to insulin.
2427 12941763 The PPAR alpha agonist fenofibrate had no effect on insulin sensitivity.
2428 12941771 We investigated the role of insulin-degrading enzyme (IDE) in amylin degradation, amyloid deposition, and cytotoxicity in RIN-m5F insulinoma cells.
2429 12941771 The IDE inhibitor bacitracin inhibited amylin degradation by 78% and insulin degradation by 100%.
2430 12941773 The present study demonstrates that the PPAR-alpha agonist fenofibrate prevents the development of diabetes in OLETF rats by reducing adiposity, improving peripheral insulin action, and exerting beneficial effects on pancreatic beta-cells.
2431 12942148 Peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands have been used for several years as modulators of insulin sensitivity and glucose metabolism.
2432 12947309 Interferon (IFN)-gamma acts synergistically with interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha to activate isoform of nitric oxide synthetase (iNOS) gene expression, induce apoptosis, and impair glucose-stimulated insulin release (GSIR) in pancreatic islets.
2433 12783775 Insulin suppresses hepatic glucose production by inhibiting the expression of two gluconeogenic enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase).
2434 12783775 Furthermore, we showed that hepatic Foxo1 expression was deregulated as a result of insulin resistance in diabetic mice and that Foxo1-Delta256 interfered with Foxo1 function via competitive binding to target promoters.
2435 12855688 The phosphorylation both of Akt on serine 473 and of p42 and p44 isoforms of mitogen-activated protein kinase induced by insulin was not affected by Cre expression, indicating that the latter specifically inhibits PDK-1-dependent signaling.
2436 12855688 Both glucose uptake and the translocation of glucose transporter 4 to the plasma membrane induced by insulin as well as glucose uptake induced by a constitutively active form of phosphoinositide 3-kinase were also greatly inhibited by Cre expression in PDK-1(lox/lox) adipocytes.
2437 12937895 In vitro effects of insulin (120 nmol/l) or AICAR (1 mmol/l) on p38 MAPK expression and phosphorylation were determined in skeletal muscle from non-diabetic (n=6) and Type 2 diabetic (n=9) subjects. p38 MAPK protein expression was similar between Type 2 diabetic patients and non-diabetic subjects.
2438 12937895 Insulin increases p38 MAPK phosphorylation in skeletal muscle from non-diabetic subjects, but not in Type 2 diabetic patients.
2439 12937895 Thus, aberrant p38 MAPK signalling might contribute to the pathogenesis of insulin resistance.
2440 13680124 In primary beta cells, glucagon and GLP-1 synergistically potentiate the stimulatory effect of 20 mmol/l glucose on insulin release and cAMP production.
2441 13680124 This study identifies type VIII AC in insulin-secreting cells as one of the potential molecular targets for synergism between GLP-1 receptor mediated and glucose-mediated signalling.
2442 14506616 Serum levels and liver mRNA expression of IGF-I determined by ribonuclease protection assay, plasma and pituitary growth hormone (GH), plasma insulin, and glycemia were also measured in both D populations.
2443 14509268 We conclude that dexamethasone inhibits insulin expression in pancreatic beta-cells via a mechanism involving down-regulation of Pdx-1 and induction of C/EBPbeta.
2444 14510865 Leptin may be a marker of risk of CHD, at least in men, and contribute to the CHD risk profile in subjects with insulin resistance.
2445 14510866 Stimulated levels of cGMP accumulation were completely abrogated by NOS inhibitor, indicating NO involvement in the effects of insulin and lyso-PC.
2446 14510866 Cell subfractionation studies demonstrate that insulin and lyso-PC each alone induced translocation of eNOS from the membrane to the cytosolic compartment and together caused a synergistic translocation.
2447 14510911 Insulin and leptin were significantly associated with GHBP, both in women (r=0.48, P<0.001 and r=0.43, P=0.001, respectively) and in men (r=0.40, P=0.01 and r=0.34, P=0.03, respectively).
2448 14514588 Additionally, changes in beta-cell sensitivity to glucose, peripheral tissue sensitivity to insulin, and changes in plasma ghrelin levels were examined.
2449 14514592 Glucagon-like peptide 1 (GLP-1) is an incretin that augments insulin secretion after meal intake and is developed for treatment of type 2 diabetes.
2450 14514592 -GLP-1 markedly augmented insulin secretion, despite lower glucose.
2451 14514596 Leptin and tumor necrosis factor (TNF)-alpha are associated with insulin resistance and cardiovascular disease.
2452 14514604 Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) exert important effects on beta-cells to stimulate glucose-dependent insulin secretion.
2453 14514630 The present study suggests that whereas GH plays a major role in inducing insulin resistance, IGF-1 may have a direct modulatory role.
2454 14514635 Exposure of selected nestin+ cells to nicotinamide, hepatocyte growth factor/scatter factor, betacellulin, activin A, or exendin-4 failed to induce pancreatic and duodenal homeobox gene-1 or insulin message as determined by RT-PCR.
2455 14514640 Phosphatidylinositol 3-kinase (PI3K) activation by insulin increases sterol regulatory element-binding protein (SREBP)-1 and LDLr expression and inhibits apoB secretion in hepatocytes.
2456 14514640 Insulin and naringenin induced PI3K-dependent increases in cytosolic and nuclear SREBP-1 and LDLr expression.
2457 14514640 Reductions in HepG2 cell media apoB with naringenin were partially attenuated by wortmannin, whereas the effect of insulin was completely blocked.
2458 14514640 Although this pathway may not regulate apoB secretion in primary hepatocytes, PI3K activation by this novel mechanism may explain the insulin-like effects of naringenin in vivo.
2459 14514641 Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, decreased insulin-stimulated expression of alpha-SMA mRNA by 26% and protein by 48% but had no effect on VSMC migration.
2460 14514641 PD98059, a mitogen-activated protein kinase (MAPK) kinase inhibitor, decreased insulin-induced VSMC migration by 52% but did not affect alpha-SMA levels.
2461 14514641 Furthermore, insulin increased alpha-SMA mRNA and protein levels to 111 and 118%, respectively, after PDGF-induced dedifferentiation, an effect inhibited by wortmannin.
2462 14514641 In conclusion, insulin's ability to maintain VSMC quiescence and reverse the dedifferentiating influence of PDGF is mediated via the PI3K pathway, whereas insulin promotes VSMC migration via the MAPK pathway.
2463 14515181 Moreover, insulin, as we have previously shown, directly stimulates PAI-1 production with a mechanism underlying a complex signaling network which ultimately leads to ERK activation.
2464 14515181 The high affinity PPARalpha agonist, Wy-14,643, increased basal and insulin-stimulated PAI-1 antigen release with a mechanism involving gene transcription.
2465 14515181 Interestingly, the addition of p38 inhibitor followed by insulin and Wy-14,643 resulted in a greater than additive stimulation of PAI-1 secretion acting through ERK1/2 phosphorylation.
2466 14515181 In conclusion, Wy-14,643 induces PAI-1 gene expression, in the presence or absence of insulin, with a mechanism which is independent on PPARalpha activation and requires signaling through the ERK1/2 signaling pathway.
2467 14516196 Protein tyrosine phosphatase 1B (PTP1B) has been implicated in the regulation of the insulin signaling pathway and represents an attractive target for the design of inhibitors in the treatment of type 2 diabetes and obesity.
2468 14517799 Insulin sensitivity was normal and levels of circulating insulin and insulin messenger RNA transcripts were appropriately reduced in gastrin -/- mice.
2469 14517946 Given its central role in the regulation of insulin release, it is understandable that mutations in the gene encoding glucokinase (GCK) can cause both hyperglycemia and hypoglycemia.
2470 14519091 Protein tyrosine phosphatase 1B inhibitors that relieve the negative control on insulin action and are active in cell assays, dipeptidyl peptidase IV inhibitors that raise postprandial glucagon-like peptide 1 levels in animals and humans, and pyruvate dehydrogenase kinase inhibitors that increase the levels of pyruvate dehydrogenase, which in turn improve insulin sensitivity, were all discussed.
2471 14521933 Hepatocyte nuclear factor 1 (HNF1), which is encoded by the MODY3 gene, has been shown to bind the insulin promoter.
2472 14536066 The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is highly expressed in adipose tissue and the presumed molecular target for antidiabetic thiazolidinedione drugs that reverse insulin resistance but also promote weight gain.
2473 14536066 Remarkably, however, genetic prevention of PPARgamma phosphorylation preserves insulin sensitivity in the setting of diet-induced obesity.
2474 14536066 Compounds that prevent PPARgamma phosphorylation or ligands that induce the conformation of nonphosphorylated PPARgamma may selectively enhance insulin sensitivity without increasing body weight.
2475 14550282 Here we tested the hypothesis that the novel analog [LysB3, GluB29] insulin (insulin glulisine, IG) might mediate an enhanced beta-cell protective effect due to its unique property of preferential IRS-2 phosphorylation.
2476 14550286 Adipokines such as Plasminogen activator inhibitor-1 (PAI-1), interleukin (IL)-8, and tumor necrosis factor (TNF)-alpha are elevated in patients with obesity, insulin resistance, and type 2 diabetes.
2477 14550293 Therefore, caution should be exercised in interpreting resistin as a link between obesity and insulin resistance in humans.
2478 14553825 The effect of obesity and insulin resistance on the development of atherosclerosis was evaluated in apoE-deficient (ApoE(-/-)) mice.
2479 12747810 A superior increase in sex-hormone-binding-globuline (SHBG) levels was evidenced in the paroxetine group (p = 0.01) as a sign of improved insulin sensitivity.
2480 12848900 Fasting and diabetes are characterized by elevated glucocorticoids and reduced insulin, leptin, elevated hypothalamic AGRP and NPY mRNA, and reduced hypothalamic POMC mRNA.
2481 12909611 Exercise synergistically enhanced insulin-stimulated insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity (P < 0.05) and Akt Ser473 phosphorylation (P < 0.05) in nondiabetic subjects but had little effect in diabetic subjects.
2482 12933346 We conclude that higher levels of MHC-beta and dephosphorylated PLB may contribute to more contractile dysfunction in male than in female diabetic rat hearts, and that phosphorylation of PLB at threonine 17 is more responsive to insulin in female diabetic rat hearts.
2483 12933352 This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM.
2484 12941959 Using transgenic mice expressing activated calcineurin in skeletal muscle, we report that skeletal muscle reprogramming by calcineurin activation leads to improved insulin-stimulated 2-deoxyglucose uptake in extensor digitorum longus (EDL) muscles compared with wild-type mice, concomitant with increased protein expression of the insulin receptor, Akt, glucose transporter 4, and peroxisome proliferator-activated receptor-gamma co-activator 1.
2485 12944390 Using phospho-specific antibodies, we observed that either adiponectin or insulin treatment (but not LPA treatment) caused phosphorylation of both Akt at Ser473 and endothelial nitric-oxide synthase (eNOS) at Ser1179 that was inhibitable by wortmannin.
2486 12952969 This effect of IL-6 was accompanied by a marked reduction in IRS-1, but not IRS-2, protein expression, and insulin-stimulated tyrosine phosphorylation, whereas no inhibitory effect was seen on the insulin receptor tyrosine phosphorylation.
2487 12952969 Consistent with the reduced GLUT-4 mRNA, insulin-stimulated glucose transport was also significantly reduced by IL-6.
2488 12952969 These results show that IL-6, through effects on gene transcription, is capable of impairing insulin signaling and action but, in contrast to TNF-alpha, IL-6 does not increase pS-307 (or pS-612) of IRS-1.
2489 12970367 We have investigated the effects of two heat shock proteins, Hsp10 and Hsp60, on insulin-like growth factor-1 receptor (IGF-1R) signaling in cardiac muscle cells.
2490 14500548 Since glucokinase expression in skeletal muscle of transgenic mice increases glucose phosphorylation, we examined whether such mice counteract the obesity and insulin resistance induced by 12 wk of a high-fat diet.
2491 14551245 Because chronic insulin can increase the levels of phosphatidylinositol 3 (PI3) kinase in several models of hyperinsulinemia, we also tested the potential involvement of this enzyme in mechanisms leading to increased cell motility.
2492 12923232 Because insulin may also regulate lipogenesis through SREBP1c and fatty acid synthase (FAS), we investigated the effect of an LXR ligand in hyperinsulinemic mice.
2493 12960081 Under euglycemic and hyperglycemic conditions, basal and insulin-stimulated action on phosphatidylinositol (PI) 3-kinase, protein kinase B/Akt, and ERK were reduced in GK rats, whereas insulin-stimulated protein kinase C (PKC)zeta activity was not altered.
2494 12960095 The peptide hormone, glucagon-like peptide 1 (GLP-1), has been shown to increase glucose-dependent insulin secretion, enhance insulin gene transcription, expand islet cell mass, and inhibit beta-cell apoptosis in animal models of diabetes.
2495 12960095 Intracellular insulin content was markedly enhanced in islets cultured with GLP-1 vs. control (P < 0.001, at d 5), and there was a parallel GLP-1-dependent potentiation of glucose-dependent insulin secretion (P < 0.01 at d 3; P < 0.05 at d 5).
2496 12970157 Recent work suggests that the melanocortin system is involved in this integration; specifically, central administration of melanocyte-stimulating hormone (MSH) decreases, whereas lack of central MSH signaling increases, peripheral insulin resistance.
2497 12970360 Insulin-stimulated association of PI3K with IRS-1 and IRS-2, and PI3K activity were reduced by HGA in parallel with the changes in IRS tyrosine phosphorylation, while Grb2-IRS association was unchanged.
2498 12970362 However, basal and insulin stimulated expression of GLUT4 in epididymal WAT is reduced only in mice carrying ablation of the LXR alpha isoform.
2499 12970579 Despite these alterations in insulin regulation and responsiveness, pregnant AhR females did not have abnormal glucose tolerance tests and did not develop hyperglycemia, classic characteristics of gestational diabetes.
2500 12970579 While the ultimate cause of the neonatal phenotype remains unclear, these studies establish that the AhR is required for normal insulin regulation in pregnant and older mice and for cardiac development in embryonic mice.
2501 12974673 While inhibition of calpain did not affect the insulin-mediated proximal steps of the phosphoinositide 3-kinase pathway, it did prevent the insulin-stimulated cortical actin reorganization required for GLUT4 translocation.
2502 12974673 Specific inhibition of calpain 10 by antisense expression reduced insulin-stimulated GLUT4 translocation and actin reorganization.
2503 14500580 The activity of FOXO proteins is principally regulated by activation of protein kinase B (PKB)/Akt by insulin and other cytokines.
2504 14500580 In the present study we mutated Leu375 to alanine in the nuclear export signal of Foxo1 (mouse FOXO1), so that it would remain in the nucleus of H4IIE rat hepatoma cells after insulin treatment, and determined whether insulin could still inhibit transcription stimulated by the Foxo1 mutant.
2505 14504291 Class IA phosphoinositide (PI) 3-kinase is composed of a p110 catalytic subunit and a p85 regulatory subunit and plays a pivotal role in insulin signaling.
2506 14504291 These cells have a 50% decrease in PI 3-kinase activity and a 30% decrease in Akt activity, leading to decreased insulin-induced glucose uptake and anti-apoptosis.
2507 14504291 Pik3r2-/- (p85 beta-/-) cells show a 25% reduction of p85 protein but normal levels of p85-p110 and PI 3-kinase activity, supporting the fact that p85 is more abundant than p110 in wild type. p85 beta-/- cells, however, exhibit significantly increased insulin-induced Akt activation, leading to increased anti-apoptosis.
2508 14504291 Indeed, both p85 alpha-/- cells and p85 beta-/- cells exhibit significantly increased insulin-induced glycogen synthase activation. p85 alpha-/- cells show decreased insulin-stimulated Jun N-terminal kinase activity, which is restored by expression of p85 alpha, p85 beta, or a p85 mutant that does not bind to p110, indicating the existence of p85-dependent, but PI 3-kinase-independent, signaling pathway.
2509 14505487 Previous work showed that acute stimulation of a conditionally active protein kinase B (PKB or cAKT) was sufficient to elicit insulin-like induction of GCK (glucokinase) and SREBP1 (sterol regulatory element-binding protein 1) in hepatocytes [Iynedjian, Roth, Fleischmann and Gjinovci (2000) Biochem.
2510 14505487 This resulted in the inhibition of insulin-dependent increases in GCK and SREBP1 mRNAs.
2511 14505487 A PKB-CaaX fusion protein, which can act as a dominant-negative inhibitor of PKB activation in other cells, was shown to be constitutively activated in hepatocytes and to trigger insulin-like induction of GCK and SREBP1.
2512 14505487 The stimulation of gene expression by constitutively active PKB-CaaX and inhibition of the insulin effect by ceramide are compatible with a role for PKB in the insulin-dependent induction of GCK and SREBP1.
2513 14534319 Taken together, these data suggest that up-regulation of CREM repressors by either FFA or high glucose exacerbates beta-cell failure in type 2 diabetes by suppressing insulin gene transcription.
2514 14517715 Diabetes can impact bone through multiple pathways, some with contradictory effects, including obesity, changes in insulin levels, higher concentrations of advanced glycation end products in collagen, hypercalciuria associated with glycosuria, reduced renal function, lower insulin-like growth factor-I, microangiopathy, and inflammation.
2515 14551916 We examined 35 genes predicted to have their major influence on insulin action, and three (9%)-INSR, PIK3R1, and SOS1-showed significant associations with diabetes.
2516 12971908 The results in the present study showed that: (1) the plasma levels of NOx in both diabetic rats were low compared to those in control rats, (2) the hippocampal NOx levels in both diabetic rats were almost the same as those in control rats, while the levels of 5-HT and DA were low in the diabetics, and (3) a sudden decrease in the plasma glucose level due to insulin administration reduced the NOx level as well as enhanced the 5-HT level in the diabetic hippocampus, a finding consistent with the results of 7 days administration of insulin.
2517 14500573 This compound improves insulin sensitivity through the activation of the nuclear receptor, peroxisome proliferator-activated receptor-gamma (PPAR-gamma).
2518 14532170 Acute or chronic activation of AMP-activated protein kinase (AMPK) increases insulin sensitivity.
2519 14532170 These data suggest that impaired insulin action on glycogen synthesis and lipid oxidation in skeletal muscle of obese type 2 diabetic subjects is unlikely to involve changes in AMPK expression and activity.
2520 14613923 This increase in life span in hIAPPxRIP-Tag was positively correlated with body weight (r = 0.48, P < 0.05) and was associated with decreased insulin sensitivity compared with RIP-Tag mice. hIAPPxRIP-Tag mice did not develop amyloid during their 4-mo life span, suggesting that increased hIAPP secretion is insufficient for islet amyloid formation within such a short time.
2521 14962991 Tacrolimus suppressed insulin secretion induced by carbachol and by a protein kinase C agonist in the presence or absence of extracellular Ca(2+).
2522 14962997 Resistin is an adipose-derived hormone that has been proposed as a link among obesity, insulin resistance, and diabetes.
2523 14722023 Insulin and the new, long-acting insulin analog glargine interacted with the IGF-IR with thousand- and hundred-fold less potency than IGF-I itself.
2524 14722023 Phosphorylation of the IGF-IR beta-subunit was shown in HAEC for IGF-I (10(-8) M) and insulin (10(-6) M) and in HMVEC for IGF-I and glargine (10(-8) M, 10(-6) M).
2525 14749206 The change in serum adiponectin concentration was inversely correlated with the change in fasting serum insulin concentration and liver fat content.
2526 14871885 We have recently shown that forced increases in AMPK activity inhibit insulin secretion from MIN6 cells (da Silva Xavier G, Leclerc I, Varadi A, Tsuboi T, Moule SK, and Rutter GA.
2527 14871885 Here, we explore whether 1) glucose, metformin, or leptin regulates AMPK activity in isolated islets from rodent and human and 2) whether changes in AMPK activity modulate insulin secretion from human islets.
2528 14871885 Incubation with metformin (0.2-1 mM) activated AMPK in both human islets and MIN6 beta-cells in parallel with an inhibition of insulin secretion, whereas leptin (10-100 nM) was without effect in MIN6 cells.
2529 14976144 Functional studies show that p35 stimulates the activity of the insulin promoter and that the stimulation requires CDK5 because stimulation is blocked by roscovitine, an inhibitor of CDK5 activity, a dominant negative form of CDK5, and small interfering RNAs against p35.
2530 14978192 Finally, benzylamine was unable to stimulate insulin secretion by isolated pancreatic islets from both species and SSAO activity was hardly detectable in pancreas.
2531 14988395 In intact cells, SREBP-2 is phosphorylated by insulin, which seems to be related to their bio-responses on low density lipoprotein receptor activity.
2532 14988395 These results suggest that activation of Erk-MAPK pathways by hormones such as insulin might be related to a novel regulatory principle of SREBP-2.
2533 15001545 PDX-1 interacts with multiple transcription factors and coregulators, including the coactivator p300, to activate the transcription of the insulin gene and other target genes within pancreatic beta-cells.
2534 15001545 Several mutant PDX-1 proteins that are associated with heritable forms of diabetes in humans, in particular the mutant P63fsdelC, exhibited increased binding to a carboxy-terminal segment of p300 in the setting of decreased DNA-binding activities, suggesting that sequestration of p300 by mutant PDX-1 proteins may be an additional mechanism by which insulin gene expression is reduced in heterozygous carriers of pdx-1(ipf-1) mutations.
2535 15001545 The introduction of the point mutations S66A/Y68A in the highly conserved amino-terminal PDX-1 transactivation domain reduced the ability of PDX-1 to interact with p300, substantially diminished the transcriptional activation of PDX-1, and reduced the synergistic activation of glucose-responsive insulin promoter enhancer sequences by PDX-1, E12, and E47.
2536 15001545 Impairment of interactions between PDX-1 and p300 in pancreatic beta-cells may limit insulin production and lead to the development of diabetes.
2537 15024017 In particular, PTP1B has been the focus of many academic and industrial laboratories because it was found to be an important negative regulator of insulin and leptin signaling, and hence a potential therapeutic target in diabetes and obesity.
2538 15024400 Taken collectively, plasma resistin concentration, before and after PIO treatment, correlated positively with hepatic fat content (r=0.66, P<0.001) and EGP during the insulin clamp (r=0.41, P<0.05).
2539 15024400 However, the plasma resistin concentration did not correlate with whole body glucose disposal (Rd) during the insulin clamp either before (r=-0.18, P=NS) or after (r=-0.13, P=NS) PIO treatment.
2540 15024400 The decrease in plasma resistin is positively correlated with the decrease in hepatic fat content and improvement in hepatic insulin sensitivity.
2541 15031294 Previous studies implicate protein-tyrosine phosphatase 1B (PTP1B) and leukocyte antigen-related phosphatase (LAR) as negative regulators of insulin signaling.
2542 15031294 Insulin-stimulated insulin receptor (IR) tyrosyl phosphorylation and phosphatidylinositol 3'-kinase activity were impaired by 35% and 40-60% in muscle of PTP1B-overexpressing mice compared with controls.
2543 15031294 Overexpression of PTP1B or LAR alone in muscle caused similar impairments in insulin action; however, compound overexpression achieved by crossing PTP1B- and LAR-overexpressing mice was not additive.
2544 15031294 Lack of additive impairment of insulin signaling by PTP1B and LAR suggests that these PTPs have overlapping actions in causing insulin resistance in vivo.
2545 15059968 In this model, insulin stimulated Grb14 expression, while TNF-alpha increased ZIP expression.
2546 15127200 Oxidative stress induces insulin resistance by impairing IRS-1 phosphorylation and PI 3-kinase activation in the LDM fraction, and NF-kappa B activation is likely to be involved in this process.
2547 15127202 The effects of insulin on gene expression were markedly altered in the muscle of Type 2 diabetic patients except for adiponectin receptor-1 and pyruvate dehydrogenase 4 mRNAs.
2548 15140033 Interestingly, co-segregation of this IGF1 194 bp allele affected the risk of INS alleles.
2549 15140063 Expression of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) mRNA were detected by real-time reverse transcriptase polymerase chain reaction and IFN-gamma, IL-10 and IL-13 by enzyme-linked immunosorbent assay in cell supernatant after stimulation with a glutamic acid decarboxylase 65 (GAD(65))-peptide [amino acid (a.a.) 247-279], insulin, the ABBOS-peptide (a.a. 152-169), phytohaemagglutinin and keyhole limpet haemocyanin.
2550 15140754 Glucagon-like peptide 1 (GLP-1) is an intestine-derived insulinotropic hormone that stimulates glucose-dependent insulin production and secretion from pancreatic beta-cells.
2551 15140755 These effects, in addition to the stimulation of insulin secretion, suggest a broad role for GLP-1 as a mediator of postprandial glucose homeostasis.
2552 15140755 Whereas other insulinotropic gastrointestinal hormones are relatively ineffective in stimulating insulin secretion in persons with type 2 diabetes, GLP-1 retains this action and is very effective in lowering blood glucose levels in these patients.
2553 15143198 Furthermore, in vivo insulin-induced activation of the protein kinase Akt is enhanced in skeletal muscle and liver from mice lacking phosphatidylinositol 5-phosphate 4-kinase beta.
2554 15143860 Agonists of glucagon-like-peptide 1 (GLP-1) and antagonists of dipeptidylpeptidase IV, which inactivates GLP-1, stimulate glucose-dependent insulin secretion, improve hyperglycemia and are already tested in clinical trials.
2555 15144884 However, the role of Pdx-1 in the regulation of insulin release is not well established.
2556 15144884 In the present study, we identified a new target of Pdx-1 involved in insulin release.
2557 15144884 Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus.
2558 15149729 We have also established that the neuronal isoform of constitutive NO synthase (nNOS) is expressed in beta-cells and modulates insulin secretion.
2559 15149729 In this study, we explored the kinetics of glucose- and arginine-stimulated insulin release in perifused isolated islets as well as the effect of N-omega-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, to get insight into the possible mechanisms responsible for the arginine hypersensitivity observed in vitro in this and other models of type 2 diabetes.
2560 15149866 Adiponectin plays a crucial role in the association between obesity, type 2 diabetes, and insulin resistance.
2561 15153417 These events appear to correlate with pdx-1 gene expression and its ability to bind the insulin gene.
2562 15153564 As expected, phosphatidylinositol 3 kinase activity (PI3K) was suppressed in muscle; in addition to decreased insulin, the mechanism includes IRS-1 phosphorylation at serine-307.
2563 15155141 Glucagon-like peptide-1 (GLP-1) is a peptide hormone from the gut that stimulates insulin secretion and protects beta-cells, inhibits glucagon secretion and gastric emptying, and reduces appetite and food intake.
2564 15155948 Infusion of a resistin mutant, lacking the intertrimer disulfide bonds, in pancreatic-insulin clamp studies reveals substantially more potent effects on hepatic insulin sensitivity than those observed with wild-type resistin.
2565 15161746 Effects of diverse stimuli, including insulin, muscle contraction, and phorbol 12-myristate-13-acetate (PMA), were determined on phosphorylation of mitogen-activated protein kinase (MAPK) signaling modules (c-Jun NH(2)-terminal kinase [JNK], p38 MAPK, and extracellular signal-related kinase [ERK1/2]) in skeletal muscle from lean and ob/ob mice.
2566 15161746 Insulin increased phosphorylation of JNK, p38 MAPK, and ERK1/2 in isolated extensor digitorum longus (EDL) and soleus muscle from lean mice in a time- and dose-dependent manner.
2567 15161746 In conclusion, insulin, contraction, and PMA activate MAPK signaling in skeletal muscle.
2568 15161746 Insulin-mediated responses on MAPK signaling are impaired in skeletal muscle from ob/ob mice, whereas the effect of contraction is generally well preserved.
2569 15161747 Here we show that insulin-stimulated glucose transport is increased in the skeletal muscle and white adipose tissue (WAT) of chow-fed DGAT1-deficient mice.
2570 15161750 We previously showed that pancreatic beta-cells express a neuronal isoform of nitric oxide synthase (nNOS) that controls insulin secretion by exerting two enzymatic activities: nitric oxide (NO) production and cytochrome c reductase activity.
2571 15161757 In conclusion, these data strongly suggest that insulin can negatively control pancreatic somatostatin mRNA and hormone content and positively control CCK(B)R mRNA; the CCK(B)R protein appears to be delayed.
2572 15161761 In SH-SY5Y cells, only the combination of insulin and C-peptide normalized posttranslational O-linked N-acetylglucosamine modifications and maximized serine phosphorylation of ankyrin(G) and p85 binding to caspr.
2573 15161768 We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects.
2574 15161768 In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018).
2575 15161768 We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010).
2576 15161768 The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019).
2577 15161768 The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele.
2578 15161789 We have tested whether the Pro12Ala variant of the peroxisome proliferator-activated receptor (PPAR)-gamma nuclear receptor involved in thiazolidinedione (TZD) action accounted for the failure of troglitazone to increase insulin sensitivity in nondiabetic Hispanic women with previous gestational diabetes treated in the Troglitazone in Prevention of Diabetes (TRIPOD) study.
2579 15161789 Among young Hispanic women at high risk for type 2 diabetes, the Pro12Ala variant of the PPAR-gamma receptor gene did not explain the failure of approximately 1/3 of subjects to increase their insulin sensitivity when placed on troglitazone at a dose of 400 mg/day.
2580 14970003 In vitro studies with hepatocytes derived from 10-wk ZDF rats showed minimal insulin dose effects on apoB secretion compared with the response and sensitivity of hepatocytes derived from 20-wk ZDF and control lean rats.
2581 15010337 Although a pharmacological dose of insulin produces a dramatic increase in phosphorylation and activity of Akt isoforms 1 and 2 in mammalian skeletal muscle, few studies have examined the effect of physiological concentrations of insulin on the phosphorylation of Akt-1 and -2 in normal and diabetic tissue.
2582 15010337 Thus a physiological concentration of insulin stimulated Akt-1 and Akt-2 phosphorylation in human skeletal muscle in the absence of hyperglycemia, but Akt-2 expression and stimulation appeared to be impaired in muscle of obese patients with atypical diabetes presenting with severe hyperglycemia.
2583 15026305 PDK-2 mRNA level in gastrocnemius muscle was not altered by insulin or FFA (i.e., Intralipid infusion).
2584 15026305 In contrast, PDK-4 mRNA level was decreased 72% by insulin (P < 0.05), and Intralipid infusion prevented only 20% of the decrease.
2585 15026305 PDK-4 protein level was decreased approximately 20% by insulin (P < 0.05), but this effect was not altered by Intralipid infusion.
2586 15026305 In conclusion, the present data indicate that insulin had a profound effect to suppress PDK-4 expression in skeletal muscle and that, contrary to previous suggestions, circulating FFA had little impact on PDK-4 mRNA expression, at least within 5 h.
2587 15059948 Furthermore, we provide the first direct in vivo evidence that an agonist of both PPARalpha and PPARgamma increases the ability of WAT, liver, and skeletal muscle to use fatty acids in association with its beneficial effects on insulin action in this model.
2588 15059949 We studied the effects of genetic background on the phenotype of ob/ob mice, a model of severe obesity, insulin resistance, and diabetes caused by leptin deficiency.
2589 15069077 We previously identified an insulin response element in the promoter of plasminogen activator inhibitor 1 (PAI-1) that was activated by an unidentified member of the forkhead/winged helix (Fox) family of transcription factors.
2590 15171688 TRH increases insulin production in cultured beta-cells, suggesting that it might play a role in regulating pancreatic beta-cell function.
2591 15039452 In an oral glucose tolerance test on day 1, the coadministration caused a greater improvement of glucose tolerance and a prominent increase of plasma active GLP-1 without marked insulin secretion.
2592 15128745 Diabetic animals exhibited increased vascular expression of Txnip and reduced thioredoxin activity, which normalized with insulin treatment.
2593 15131120 Nine proteins, including vimentin, EH-domain-containing protein 2, elongation factor 2, glucose-regulated protein 78, transketolase, and succinyl-CoA transferase were primarily affected by presence or absence of insulin signaling, whereas 21 proteins, including myosin non-muscle form A, annexin 2, annexin A6, and Hsp47 were regulated in relation to adipocyte size.
2594 15142986 Human mutations in HNF1alpha or HNF1beta lead to maturity-onset diabetes of the young (MODY3 and MODY5, respectively), and patients present with impaired glucose-stimulated insulin secretion.
2595 15150650 In conclusion, a genetic variant of the LAR gene promoter is consistently associated with features of insulin resistance in two different Caucasian populations.
2596 15151993 In conclusion, loss of PDX1 function alters expression of mitochondrially encoded genes through regulation of TFAM leading to impaired insulin secretion.
2597 15211372 Adipose tissue is now considered as an endocrine and secretory organ, and some adipocyte factors are thought to play a major role in the induction of insulin resistance in skeletal muscle.
2598 15211372 Conditioned medium lacking the perturbation of insulin signalling did not activate NF-kappaB.
2599 15211372 The IKK inhibitor I229 did not affect protein expression of Akt, but fully restored insulin action in myocytes subjected to co-culture.
2600 15240578 Contrary to expectation, intensive insulin therapy suppressed serum IGF-I, IGFBP-3, and acid-labile subunit concentrations.
2601 15240629 Protein kinase B (PKB) expression and phosphorylated PKB levels in response to insulin stimulation (20 nm) were comparable in the diabetic and control cultures. 5-Amino-4-imidazolecarboxamide riboside (AICAR) mimics the effect of exercise on glucose uptake by activating AMP-activated protein kinase.
2602 15240633 The mean plasma glucose excursion was reduced by 90%, falling into the normal range, after breakfast, whereas plasma pancreatic polypeptide, glucagon, and acetaminophen levels were reduced, and insulin levels were not affected.
2603 15240650 The proinflammatory cytokines TNFalpha, IL-6, and IL-8 are released from the placenta at term and have been implicated in and/or associated with various metabolic events, including decreased insulin sensitivity.
2604 15240880 Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling.
2605 15242186 In this paper, we present the effects of two organic fractions and two aqueous extracts from the leaves of S. sonchifolius on rat hepatocyte viability, on oxidative damage induced by tert-butyl hydroperoxide (t-BH) and allyl alcohol (AA), and on glucose metabolism and their insulin-like effect on the expression of cytochrome P450 (CYP) mRNA.
2606 15242818 Two mammalian insulin secreting pancreatic beta-cell lines BRIN BD11h2E1 and INS-1h2E1, which express human full length CYP2E1 cDNA, were used to elucidate the role of CYP2E1-mediated nitrosamine bioactivation in pancreatic beta-cell dysfunction and destruction.
2607 15249791 Subjects with both obesity and high BP showed greater expression of lipid and glucose abnormalities, higher urinary albumin excretion, and greater prevalence of prediabetes, undetected type 2 diabetes, and insulin resistance syndrome.
2608 15254873 After insulin administration in the fast state, tyrosine phosphorylation of IR and association of IRS-2 with PI3-K were higher in the EH and CL groups than in the CH group.
2609 15255786 Lipoprotein lipase activity (LPL) was calculated as the triacylglycerol (TAG) flux across AD, and hormone-sensitive lipase (HSL) as the glycerol flux minus LPL. (1) In T2D the increase in prandial insulin secretion was delayed; postprandial nonesterified fatty acid (NEFA) and TAG levels in blood were increased, while BF, LPL and TAG clearance were blunted vs.
2610 15255786 CON. (2) Acute or chronic nateglinide treatment induced a prompt increase in prandial insulin secretion, resulting in a decrease in blood glucose and NEFA levels owing to suppression of HSL, while BF, LPL and TAG clearance remained suppressed.
2611 15257162 However, when compared with placebo, ACE inhibition by ramipril or by the ARB, candesartan, both decrease the incidence of new diabetes, raising the hypothesis that these agents actually prevent the changes leading to insulin resistance, possibly by lessening the adverse effects of angiotensin II on the endothelium.
2612 15264018 Since insulin stimulates GLUT4 translocation to the plasma membrane, percent GLUT4 in plasma membrane was divided by the insulinemia at the time of tissue removal and was found to be reduced by 75% (P < 0.01) in obese compared to control dogs.
2613 15264018 We conclude that the insulin-stimulated translocation of GLUT4 to the cell surface is reduced in obese female dogs.
2614 15149950 IL-6 and TNF-alpha have been associated with insulin resistance and type 2 diabetes.
2615 15149950 Furthermore, in the presence of insulin, IL-6 reduced the esterification of FA to triacylglycerol by 22% (P < 0.05).
2616 15149950 In conclusion, the results demonstrate that IL-6 plays an important role in regulating fat metabolism in muscle, increasing rates of FA oxidation, and attenuating insulin's lipogenic effects.
2617 15149955 Inhibition of IDS by antisense infection led to an increase in lysosomal size and a high rate of insulin granule degradation via the crinophagic route in pancreatic beta-cells.
2618 15231875 Although insulin caused a discernible increase in cell surface IRAP content of G4H-/- cardiomyocytes, cell surface IRAP remained 70% lower than insulin-stimulated controls.
2619 15319424 Immunohistochemistry observed via TIRFM showed that the number of docked insulin granules was decreased by 60% in beta-cells treated with IL-1beta, while it was not affected by exposure to IFN-gamma.
2620 15448084 Here we present novel evidence that early interventions aimed at reducing oxidative stress of pancreatic cells and islets through the use of the catalytic antioxidant probe AEOL10150 (manganese [III] 5,10,15,20-tetrakis [1,3,-diethyl-2imidazoyl] manganese-porphyrin pentachloride [TDE-2,5-IP]) effectively reduces NF-kappaB binding to DNA, the release of cytokines and chemokines, and PARP activation in islet cells, resulting in higher survival and better insulin release.
2621 15448088 To test the effect of activating islet-associated APCs in situ, we generated transgenic mice expressing CD154 (CD40 ligand) under control of the rat insulin promoter (RIP).
2622 15451915 Adiponectin and resistin, two recently discovered adipocyte-secreted hormones, may link obesity with insulin resistance and/or metabolic and cardiovascular risk factors.
2623 15464424 Rare monogenic mutations in PPARgamma have a limited impact on the health of the population due to their low frequency but are associated with severe phenotypes such as severe insulin resistance, partial lipodystrophy, type 2 diabetes and hypertension.
2624 15465639 Culture with TNF-alpha increased activity of both SULT 1A1 and 1A3 in the HT-29 cells; TGF-beta also increased activities of both isoforms but to a lesser extent; insulin increased activity of SULT 1A1 only.
2625 15465737 Furthermore, plasma leptin was positively correlated with plasma insulin level (r = 0.578, P < 0.01) and body weight (r = 0.541, P < 0.05), and was inversely correlated with the blood glucose level (r = -0.46, P < 0.05).
2626 15467829 Diabetes resolved when the mice were between 6 and 10 months of age: functional beta cells expressing Irs2 repopulated the pancreas, restoring sufficient beta cell function to compensate for insulin resistance in the obese mice.
2627 15467831 Reduction of Akt activity in transgenic animals resulted in impaired glucose tolerance due to defective insulin secretion.
2628 15472206 Both drugs protected partially against loss of glucose-stimulated insulin secretion and prevented completely increased apoptosis caused by IL-1beta or 600 mg/dl glucose.
2629 15472209 Inverse correlations between indexes of insulin sensitivity and serum markers of inflammation have been observed and, particularly, TNF-alpha has been shown to be associated with the appearance of insulin resistance in pregnancy.
2630 15339744 In conclusion, insulin resistance in skeletal muscle induced by short-term GH administration is not associated with detectable changes in the upstream insulin-signaling cascade or reduction in total GLUT4.
2631 15339744 Yet unknown mechanisms in insulin signaling downstream of Akt may be responsible.
2632 15383372 Glucose-dependent insulinotropic polypeptide (GIP) regulates glucose homeostasis and high-fat diet-induced obesity and insulin resistance.
2633 15500838 Intrinsically lower and further decreased MDH activities may be factors that induce insulin resistance observed in diabetic cats.
2634 15578112 Moreover, in patients with type 2 diabetes, serum resistin levels are correlated with levels of soluble tumor necrosis factor alpha receptor, an inflammatory marker linked to obesity, insulin resistance, and atherosclerosis.
2635 15583845 Adiponectin is an adipocyte-secreted protein that is known to modulate insulin sensitivity and glucose homeostasis.
2636 15588682 Much like insulin, clove-mediated repression is reversed by PI3K inhibitors and N-acetylcysteine (NAC).
2637 15777019 Vasoactive agonists normally elevate [Ca2+]i (intracellular calcium concentration) in endothelial cells, thus stimulating NO production, whereas fluid shear stress, 17beta-oestradiol and insulin cause phosphorylation of the serine/threonine protein kinase Akt/protein kinase B in a phosphoinositide 3-kinase-dependent manner and activation of eNOS at basal [Ca2+]i levels.
2638 15803906 GLP-1 controls blood glucose following nutrient absorption via stimulation of glucose-dependent insulin secretion, insulin biosynthesis, islet proliferation, and neogenesis and inhibition of glucagon secretion.
2639 15861314 As separate activation of PPARalpha and PPARgamma improves lipid metabolism, the development of new drugs integrating PPARalpha and PPARgamma activity (PPAR-alpha/gamma agonists) is a promising line that may further improve insulin resistance, FFA metabolism, and consequently, atherogenic diabetic dyslipidemia.
2640 15895517 The present results thus indicate that CLA feeding promotes insulin resistance in obese/diabetic mice by at least inverse regulation of leptin and adiponectin, and TNFalpha, adipocytokines known to either ameliorate or deteriorate insulin sensitivity, respectively.
2641 15975085 Why diabetes would increase the likelihood of Alzheimer's disease is not immediately clear, although recent studies have demonstrated an impact of insulin abnormalities, insulin resistance and advanced glycation end products on both the development of neural amyloid plaques and neurofibrillary tangles.
2642 16035392 Peroxisome-proliferator activated receptor gamma (PPARgamma) agonists, for example the thiazolidinediones, redistribute fat within the body (decrease visceral and hepatic fat; increase subcutaneous fat) and have been shown to enhance adipocyte insulin sensitivity, inhibit lipolysis, reduce plasma FFA and favourably influence the production of adipocytokines.
2643 16114542 Rosiglitazone can reduce FPG level and serum leptin and improve the insulin resistance in patients with Type 2 diabetes.
2644 16145910 Rosiglitazone can decrease the level of serum TNF-alpha significantly and improve insulin resistance.
2645 16215105 Intriguingly, GLP-1 hormones may have important biologic actions aside from stimulating insulin release, including inhibition of gastric motility and acid secretion, suppression of glucagon secretion, and islet cell proliferation.
2646 15471944 Islet Ca2+-independent phospholipase A2 (iPLA2) is postulated to mediate insulin secretion by releasing arachidonic acid in response to insulin secretagogues.
2647 15471944 However, the significance of iPLA2 signaling in insulin secretion in vivo remains unexplored.
2648 15471944 Bromoenol lactone (BEL), a selective inhibitor of iPLA2, inhibited glucose-stimulated insulin secretion from isolated mouse islets; this inhibition was overcome by exogenous arachidonic acid.
2649 15471944 These results unambiguously demonstrate that iPLA2 signaling plays an important role in glucose-stimulated insulin secretion under physiological conditions.
2650 15522996 Resistin is an adipocyte-secreted hormone proposed to link obesity with insulin resistance and diabetes, but no previous study has performed a joint quantitative evaluation of white adipose tissue (WAT) resistin mRNA expression and serum levels in relation to insulinemia and glycemia in mice.
2651 15522996 In addition, serum resistin levels, but not resistin mRNA expression levels, are correlated with body weight, and neither resistin mRNA expression nor serum resistin levels are correlated with serum insulin or glucose levels.
2652 15547141 To determine the role of AMP-activated protein kinase (AMPK) activation on the regulation of fatty acid (FA) uptake and oxidation, we perfused rat hindquarters with 6 mM glucose, 10 microU/ml insulin, 550 microM palmitate, and [14C]palmitate during rest (R) or electrical stimulation (ES), inducing low-intensity (0.1 Hz) muscle contraction either with or without 2 mM 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
2653 15562034 We determined nitric oxide synthase (NOS) activity in skeletal muscle of 10 type 2 diabetic (hemoglobin A(1C) = 6.8 +/- 0.1%) and 11 control subjects under basal conditions and during an 80 mU/m(2).min euglycemic insulin clamp performed with vastus lateralis muscle biopsies before and after 4 h of insulin.
2654 15562034 In response to insulin, NOS activity increased 2.5-fold in controls after 4 h (934 +/- 282 pmol/min.mg protein, P < 0.05 vs. basal), whereas insulin failed to stimulate NOS activity in diabetics (86 +/- 28 pmol/min.mg protein, P = NS from basal).
2655 15562034 In controls, insulin-stimulated NOS activity correlated inversely with fasting plasma insulin concentration (r = -0.58, P = 0.05) and positively with Rd (r = 0.71, P = 0.03).
2656 15562034 In control and diabetic groups collectively, Rd correlated with insulin-stimulated NOS activity (r = 0.52, P = 0.02).
2657 15562034 We conclude that basal and insulin-stimulated muscle NOS activity is impaired in well-controlled type 2 diabetic subjects, and the defect in insulin-stimulated NOS activity correlates closely with the severity of insulin resistance.
2658 15574412 This effect was stronger in the double mutant S332A/336A(IRS-1) and led to enhanced insulin-mediated activation of protein kinase B.
2659 15574412 In summary, our studies identify Ser332 as the GSK-3 phosphorylation target in IRS-1, indicating its physiological relevance and demonstrating its novel inhibitory role in insulin signaling.
2660 15500444 Circadian expression of PPARalpha mRNA was intact in the liver of insulin-dependent diabetic and of adrenalectomized mice, suggesting that endogenous insulin and glucocorticoids are not essential for the rhythmic expression of the PPARalpha gene.
2661 15590636 Taken together, these data indicate that the G972R naturally occurring polymorphism of IRS-1 not only reduces phosphorylation of the substrate but allows IRS-1 to act as an inhibitor of the insulin receptor kinase, producing global insulin resistance.
2662 15590659 These data suggest that insulin inhibits glucagon gene transcription by signaling via PI 3-kinase and PKB, with the transcription factor Pax6 and its potential coactivator CBP being critical components of the targeted promoter-specific nucleoprotein complex.
2663 15386812 Enhanced insulin sensitivity via exercise training might be mediated by endogenous beta-endorphin through an increase of postreceptor insulin signaling related to the IRS-1-associated PI3-kinase step that leads to the enhancement of GLUT 4 translocation and improved glucose disposal in obese Zucker rats.
2664 15562250 Among the nondiabetic women, fasting insulin (r = 0.69, P < 0.01), 2-h insulin (r = 0.56, P < 0.05), and HOMA index (r = 0.59, P < 0.05) correlated positively with TNF-alpha gene expression; fasting insulin (r = 0.54, P < 0.05) was positively related to, and 2-h insulin (r = 0.49, P = 0.06) tended to be positively related to, IL-6 gene expression; and glucose area (r = -0.56, P < 0.05) was negatively related to, and insulin area (r = -0.49, P = 0.06) tended to be negatively related to, adiponectin gene expression.
2665 15562255 GLUT4+/-;PDX-1+/- mice developed beta-cell hyperplasia but failed to increase their beta-cell insulin content.
2666 15598661 Although the cause and effect relationship between FFAs and insulin resistance is complex, plasma FFA is negatively correlated with the expression of peroxisome proliferator activated receptor-gamma cofactor-1 (PGC-1) and nuclear encoded mitochondrial genes.
2667 15604213 In this study, we explored whether DPP-4 inhibition by valine-pyrrolidide (val-pyr; 100 micromol/kg administered through gastric gavage at t = -30 min) affects the insulin and glucose responses to iv glucose (1 g/kg) together with GLP-1 (10 nmol/kg), glucose-dependent insulinotropic polypeptide (GIP; 10 nmol/kg), pituitary adenylate cyclase-activating polypeptide 38 (PACAP38; 1.3 nmol/kg), or gastrin-releasing peptide (GRP; 20 nmol/kg) given at t = 0 in anesthetized C57BL/6J mice.
2668 15604213 The augmented insulin response to GRP by val-pyr was prevented by the GLP-1 receptor antagonist, exendin(3) (9-39), raising the possibility that GRP effects may occur secondary to stimulation of GLP-1 secretion.
2669 15604213 We conclude that DPP-4 inhibition augments the insulin response not only to GLP-1 but also to GIP, PACAP38, and GRP.
2670 15618349 Exposure of mouse betaTC3 insulinoma cells to the proteasome inhibitor N-Acetyl-Leu-Leu-Nle-CHO (ALLN) reduced cell viability, activated caspase-3, induced apoptosis, and suppressed insulin release.
2671 15637076 These results show that beta-cell-derived LPL has two physiologically relevant effects in islets, the inverse regulation of glucose metabolism and the independent mediation of insulin secretion through effects distal to membrane depolarization.
2672 15654602 Adenine nucleotides, mitochondrial membrane potential, the expression of UCP-2, complex I and complex V of the respiratory chain, and nitrotyrosine levels were evaluated and correlated with insulin secretion.
2673 15654602 In particular, UCP-2 expression is increased (probably due to a condition of fuel overload), which leads to lower ATP, decreased ATP/ADP ratio, with consequent reduction of insulin release.
2674 15700135 Finally, adipose tissue autotaxin expression was significantly up-regulated in patients exhibiting both insulin resistance and impaired glucose tolerance.
2675 15700135 The present work demonstrates the existence of a db/db-specific up-regulation of adipocyte autotaxin expression, which could be related to the severe type 2 diabetes phenotype and adipocyte insulin resistance, rather than excess adiposity in itself.
2676 15700136 The OPG production into the medium decreased dose- and time-dependently after insulin treatment (maximal effect approximately 60% of control) in HVSMCs, whereas TNF-alpha supplement gave rise to increased OPG synthesis in a time- and dose-dependent manner (maximal effect approximately 200% of control).
2677 15729576 The association of insulin detemir with non-esterified fatty acid binding sites on albumin may limit its transfer from the circulation into the extravascular extracellular space in adipose tissue and muscle, due to the capillary endothelial cell barrier.
2678 15735891 The hepatocyte nuclear factor (HNF)-4alpha is an orphan nuclear receptor, which plays crucial roles in regulating hepatic gluconeogenesis and insulin secretion.
2679 15749807 Previous studies in our laboratory have shown that GH induction of signal transducers and activators of transcription (STAT)5B tyrosine phosphorylation is inhibited by prolonged insulin treatment, probably via downregulation of GHR.
2680 15749807 Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone.
2681 15749807 In the present work, total STAT5B and STAT1 protein levels were not altered by prolonged insulin treatment.
2682 15749807 Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels.
2683 15752363 Stimulation of glycogen-targeted protein phosphatase 1 (PP1) activity by insulin contributes to the dephosphorylation and activation of hepatic glycogen synthase (GS) leading to an increase in glycogen synthesis.
2684 15752363 The glycogen-targeting subunits of PP1, GL and R5/PTG, are downregulated in the livers of diabetic rodents and restored by insulin treatment.
2685 15752742 These results suggest that Meg1/Grb10 inhibits the function of both insulin and IGF1 receptors in these cells, since a similar phenotype has been reported for Ir and Igf1r double knockout mice.
2686 15755688 We observed that STZ-induced diabetes promoted a significant decrease in mitochondrial CoQ9, ATPase activity, and a lower capacity of mitochondria to accumulate Ca2+ when compared with control and insulin-treated diabetic rats.
2687 15766512 Adiponectin stimulates fatty acids oxidation, reduces plasma triglycerides, and improves glucose metabolism by increasing the insulin sensitivity.
2688 15766572 The arginine-induced insulin release is via the production of nitric oxide, since treatment with N(G)-nitro-l-arginine, an inhibitor of nitric oxide synthase, blocks insulin secretion induced by l-arginine.
2689 15767618 Mean 24-hour plasma profiles of glucose levels normalized, mean hemoglobin A1c decreased from 7.3% to 6.8%, and insulin sensitivity improved by approximately 75%.
2690 15769092 The in vitro insulinotropic effect of PEG(2k)-Lys-GLP-1 showed comparable biological activity with native GLP-1 (P = 0.11) in stimulating insulin secretion in isolated rat pancreatic islet and was significantly more potent than the PEG(2k)-N(ter)-GLP-1 (P < 0.05) that showed a marked reduced potency.
2691 15772055 We suggest that regular exercise induces suppression of TNF-alpha and thereby offers protection against TNF-alpha-induced insulin resistance.
2692 15778927 This study evaluated the peroxisome proliferation-activated receptor-gamma2 ( PPAR-gamma2) Pro12Ala polymorphism and the angiotensin converting enzyme ( ACE) I/D polymorphism with respect to any potential influence that these highly prevalent polymorphisms may impose on changes in insulin sensitivity and maximal aerobic capacity induced by exercise.
2693 15780433 The actions of GLP-1 include (a) a stimulation of insulin secretion in a glucose-dependent manner, (b) a suppression of glucagon, (c) a reduction in appetite and food intake, (d) a deceleration of gastric emptying, (e) a stimulation of beta-cell neogenesis, growth and differentiation in animal and tissue culture experiments, and (f) an in vitro inhibition of beta-cell apoptosis induced by different toxins.
2694 15780434 Preservation of the insulin response to parenteral glucagon-like peptide-1 (GLP-1), contrasting with lack of stimulation of insulin secretion by the other known incretin gastric inhibitory polypeptide (GIP), prompted studies with exogenous GLP-1 in recent-onset Type 1 diabetes.
2695 15780820 Exogenous adiponectin corrects metabolic defects that are associated with insulin resistance, and might protect the endothelium from the progression of cardiovascular disease.
2696 15780823 Therefore, direct inhibition of PAI-1 might not only provide a new therapeutic strategy for reducing cardiovascular risk, but may also have beneficial effects on obesity and insulin resistance.
2697 15784408 Fasting blood samples were used to determine concentrations of TNF alpha, soluble TNF receptors 1 (sTNFR1) and 2 (sTNFR2) in the same 13 MA (7 women, 6 men, age=27.0+/-2.0 years, BMI=23.0+/-0.7) and 13 NHW (7 women, 6 men, age=24.8+/-1.5 years, BMI=22.8+/-0.6) previously shown to exhibit differences in insulin sensitivity.
2698 15585589 Resistin (Rstn) is known as an adipocyte-specific secretory factor that can cause insulin resistance and decrease adipocyte differentiation.
2699 15585589 Conversely, based on various studies, insulin-like growth factors (IGFs) can improve insulin resistance and stimulate adipocyte adipogenesis.
2700 15613682 Nevertheless, there are intrinsic abnormalities in glucose transport and insulin signaling in myotubes from affected women, including increased phosphorylation of IRS-1 Ser312, that may confer increased susceptibility to insulin resistance-inducing factors in the in vivo environment.
2701 15632103 Insulin increased the phosphorylation of Akt in all cardiomyocyte preparations (control, db/db, COOH-treated db/db) to the same extent.
2702 15632103 Thus insulin has selective metabolic actions in mouse cardiomyocytes; deoxyglucose uptake and Akt phosphorylation are increased, but fatty acid oxidation and AMPK phosphorylation are unchanged.
2703 15713666 Manganese superoxide dismutase activity in mutant mice was significantly upregulated, suggesting that the suppressed insulin signaling leads to an enhanced antioxidant defense.
2704 15743769 Chromatin immunoprecipitation assays revealed that the decrease in insulin transcription was associated with decreases in the occupancies of Pdx-1 and p300 at the proximal insulin promoter.
2705 15743769 Our results suggest that Pdx-1 directly regulates insulin transcription through formation of a complex with transcriptional coactivators on the proximal insulin promoter.
2706 15744531 Partitioning-defective protein-6alpha (Par6alpha) has recently been demonstrated to negatively regulate insulin signalling in murine myoblasts.
2707 15756539 The severely impaired proinsulin processing combined with decreased GLP-1R expression and cellular cAMP content, rather than metabolic defects or altered exocytosis, may contribute to the beta cell dysfunction induced by Pdx-1 deficiency.
2708 15761495 Our data provide genetic evidence that HNF-4alpha is required in the pancreatic beta cell for regulation of the pathway of insulin secretion dependent on the ATP-dependent potassium channel.
2709 15770466 Their development is based on the observation that DPP-IV rapidly inactivates the incretin hormone glucagon-like peptide-1 (GLP-1), which is released postprandially from the gut and increases insulin secretion.
2710 15770466 DPP-IV inhibitors stabilise endogenous GLP-1 at physiological concentrations, and induce insulin secretion in a glucose-dependent manner; therefore, they do not demonstrate any hypoglycaemic effects.
2711 15812560 Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130 +/- 27.6% (P < 0.05) similar to that induced by VEGF and with which it is additive (281 +/- 13%) (P < 0.05).
2712 15826997 Autoantibodies directed against GAD (antiGAD-Ab) have been described in patients with insulin-dependent diabetes mellitus, stiff-man syndrome, and in a few patients with progressive cerebellar ataxia.
2713 15828230 While PPARalpha potentiates fatty acid catabolism in the liver and is the molecular target of the lipid-lowering fibrates, PPARgamma is essential for adipocyte differentiation and hypertrophy, and mediates the activity of the insulin sensitizing thiazolidinediones.
2714 15836467 In support of this notion, we have shown that SCD1-deficient mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet-induced obesity and liver steatosis.
2715 15837923 Here we provide evidence that ANGPTL4 is a blood-borne hormone directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity.
2716 15837923 Serum levels of ANGPTL4 in human subjects inversely correlated with plasma glucose concentrations and HOMA IR, the homeostasis model assessment of insulin resistance.
2717 15837949 Tumor necrosis factor-alpha (TNF-alpha), an inducer of angiotensinogen in hepatocytes, is elevated in hyperinsulinemic, obese individuals and may provide a link in mediating insulin upregulation of the RAS in adipose tissue.
2718 15837949 Isolated human abdominal subcutaneous adipocytes (n=12) were treated with insulin (1 to 1000 nmol/L), insulin in combination with RSG (10 nmol/L), and RSG (10 nmol/L) alone to determine angiotensinogen expression and angiotensin II, bradykinin, and TNF-alpha secretion.
2719 15837949 Insulin increased TNF-alpha secretion in a concentration-dependent manner (P<0.01), whereas RSG (10 nmol/L) significantly reduced the insulin-mediated rise in TNF-alpha (P<0.001), as well as angiotensin and angiotensin II.
2720 15837949 This study also demonstrates a potential TNF-alpha-mediated mechanism through which insulin may stimulate the RAS and may contribute to explain obesity-associated hypertension.
2721 15839186 Treatment regimens were 1 or more of the following: insulin, thiazolidinediones, sulfonylureas, biguanides (metformin), or other less frequently used options (including meglitinides or alpha-glucosidase inhibitors).
2722 15840308 It suggests that the defect in SUR1 gene (cc and AA) may contribute to insulin hypersecretion, which might be the cause of increased body weight and decreased insulin sensitivity and genotype cc of SUR1 is connected with severe type of GDM.
2723 15842525 Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important insulinotropic hormones that enhance the insulin secretory response to feeding.
2724 15850385 Deletion of insulin-degrading enzyme (IDE) in mice causes accumulation of cerebral amyloid beta-protein (Abeta), hyperinsulinemia, and glucose intolerance.
2725 15850715 Long chain polyunsaturated fatty acids (LCPUFAs) increase cell membrane fluidity and enhance the number of insulin receptors and the affinity of insulin to its receptors; suppress TNF-alpha, IL-6, macrophage migration inhibitory factor (MIF) and leptin synthesis; increase the number of GLUT-4 receptors, serve as endogenous ligands of PPARs, modify lipolysis, and regulate the balance between pro- and anti-oxidants, and thus, play a critical role in the pathogenesis of insulin resistance.
2726 15851721 In the 63 patients admitted with isolated brain injury, the authors studied the impact of insulin therapy on intracranial pressure, diabetes insipidus, seizures, and long-term rehabilitation at 6 and 12 months follow-up.
2727 15701680 To determine the metabolic role of HSL, we examined the changes in tissue-specific insulin action and glucose metabolism in vivo during hyperinsulinemic euglycemic clamps after 3 wk of high-fat or normal chow diet in awake, HSL-deficient (HSL-KO) mice.
2728 15741607 Additionally, GLUT8 expression was studied using two different models of insulin resistance, GLUT4-/- and db/db mice.
2729 15759102 Indeed, suppression of the JNK pathway in diabetic mice improves insulin resistance and ameliorates glucose tolerance.
2730 15774766 Increases in hypothalamic corticotrophin-releasing hormone (CRH) and inhibitory hippocampal mineralocorticoid receptor (MR) mRNA with STZ diabetes were not restored with either insulin or phloridzin treatments.
2731 15831571 In insulin-secreting rat INS-1 cells cultured in the presence of 11 mm glucose, combined pharmacological blockade of L- and T-type Ca(2+) channels suppressed IL-1beta-induced in vitro phosphorylation of the JNK substrate c-jun and reduced IL-1beta-stimulated activation of JNK1/2 as assessed by immunoblotting.
2732 15831571 Our data suggest that Ca(2+) plays a permissive role in IL-1beta activation of the JNK signaling pathway in insulin-secreting cells.
2733 15834118 Adiponectin is secreted from adipocytes, and low circulating levels have been epidemiologically associated with obesity, insulin resistance, type 2 diabetes, and cardiovascular disease.
2734 15834118 Also, adiponectin increased insulin's ability to maximally stimulate glucose uptake by 78% through increased glucose transporter 4 (GLUT4) gene expression and increased GLUT4 recruitment to the plasma membrane.
2735 15845625 Semiquantitative RT-PCR analysis showed that insulin (10(4) microU/ml) alone or in combination with glucose (15 mm) markedly suppressed IRS-2 gene expression, whereas IRS-1 mRNA was unaffected by the culture conditions.
2736 15849359 IRS-1-S24D also had an impaired ability to mediate insulin-stimulated translocation of GLUT4 in rat adipose cells.
2737 15849359 TNF-alpha-regulated phosphorylation at Ser(24) in the pleckstrin homology domain of IRS-1 by mPLK/IRAK represents an additional mechanism for cross-talk between inflammatory signaling and insulin signaling that may contribute to metabolic insulin resistance.
2738 15852457 The multifaceted actions of GLP-1 include the following: (1) the stimulation of insulin secretion and of its gene expression, (2) the inhibition of glucagon secretion, (3) the inhibition of food intake, (4) the proliferation and differentiation of beta cells, and (5) the protection of beta-cells from apoptosis.
2739 15864531 Resistin is an adipokine that might link obesity and insulin resistance.
2740 15879311 Insulin stimulated protein kinase B (akt) and endothelial nitric oxide synthase (eNOS) phosphorylation were preserved in arteries from diabetic mice; however, eNOS protein dimers were markedly diminished.
2741 15887043 Exposure to rosiglitazone for 24 h induced ucp-1, lpl and hsl gene expression and when rosiglitazone was combined with insulin a synergistic effect on lpl and ucp-3 mRNA expression was produced.
2742 15894466 To determine the underlying mechanisms of these metabolic malfunctions, we studied mitochondrial respiration, uncoupled respiration and oxidative enzyme activities (citrate synthase (CS), 3-hydroxy-acyl-CoA-dehydrogenase activity (HAD)) before and after acute exposure to insulin and/or palmitate in myotubes established from healthy lean and obese subjects and T2D patients.
2743 15913829 Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling.
2744 15917853 Recent evidence suggests that adiponectin, a protein whose circulating levels are decreased in obesity, has anti-inflammatory properties, and also appears to enhance potently insulin action and therefore appears to function as a signal produced by adipose tissue that influences whole-body glucose metabolism.
2745 15921943 Neither total nor weight adjusted insulin requirements correlated to total PGH, calculated free PGH, nor GHBP.
2746 15922295 In db/db mice, oral administration of angiotensin II Type 1 receptor antagonist valsartan (5 mg/kg) for 4 weeks significantly attenuated the increased expression of gp91phox and p22phox together with inhibition of oxidative stress and partially restored decreased insulin contents in islets.
2747 15935991 Transfections of rat adipose cells demonstrate that over-expression of wild-type NSF has no effect on total, or basal and insulin-stimulated cell-surface expression of HA-tagged GLUT4.
2748 15935991 In contrast, a dominant-negative NSF (NSF-D1EQ) can be expressed at a low enough level that it has little effect on total HA-GLUT4, but does reduce both basal and insulin-stimulated cell-surface HA-GLUT4 by approximately 50% without affecting the GLUT4 fold-translocation response to insulin.
2749 15939056 We investigated whether uncontrolled diabetes and insulin therapy effect expression and function of the main enzymes of the endothelial nitric oxide (eNOS)-sGC signaling pathway in vivo.
2750 15939056 Expression and function of eNOS, sGC and protein kinase G (PKG) were studied by Western blot analysis and vasorelaxation to NO-donor in thoracic aortas from control (CON) and streptozotocin (SZT)-induced diabetic rats during uncontrolled diabetes (DM) and insulin treatment (INS) for 8 weeks.
2751 15939893 Our experiments showed that overexpression of IA-2 resulted in a 6-fold increase in glucose- or K+-induced insulin secretion and a approximately 3-fold increase in the number of secretory vesicles and the insulin content of cells.
2752 15939893 The half-life of insulin in cells overexpressing IA-2 was nearly twice as great as that in mock-transfected cells, suggesting that IA-2 was stabilizing the insulin-containing vesicles.
2753 15940042 Moreover, we used a transgene mouse model with human vascular endothelial growth factor (VEGF) production in beta-cells under the control of the rat insulin promoter (RIP) to stimulate islet EC proliferation.
2754 15945346 MIRKO mouse adipose tissue increased secretion of adiponectin that increases the insulin sensitivity and do not alter the leptin production.
2755 15946462 Increasing levels of leptin and decreasing levels of adiponectin correlate with worsening insulin resistance in obese individuals.
2756 15948674 Indeed, Kv1.3 channel inhibition increases insulin sensitivity by decreasing inflammatory cytokines and by facilitating the translocation of GLUT4 to the plasma membrane.
2757 15948675 Activation of the JNK pathway interferes with insulin action and reduces insulin biosynthesis, and suppression of the JNK pathway in diabetic mice improves insulin resistance and beta-cell function, leading to amelioration of glucose tolerance.
2758 15949766 Hyperinsulinemia-mediated inactivation of Foxa2 by nuclear exclusion has recently been implicated in the development of liver steatosis and insulin resistance in three animal models of diabetes.
2759 15950750 One function of insulin is to signal high extracellular glucose, while leptin may signal the abundance of extracellular lipid, both energy sources being readily utilized by muscle.
2760 15950750 Pretreatment of BMC for 10 min leptin, followed by insulin time-course, caused IRS-1 recruitment to be unresponsive, but evoked a rapid, phasic response of PI 3-kinase recruitment to the IR and abrogated the response of GLUT4 translocation to the plasma membrane evoked by insulin alone.
2761 15950750 Insulin alone down-regulated the leptin signaling pathway, JAK-2 association with ObR decreased at all time-points, and JAK-2 phosphorylation decreased similarly.
2762 15950750 Pretreatment with leptin followed by insulin time-course showed marked up-regulation of the early leptin signaling pathway, JAK-2 association with the ObR being increased by insulin while JAK-2 tyrosine phosphorylation was also increased.
2763 15952917 Among those, adiponectin, visfatin and omentin appear as insulin-sensitising adipocytokines, whereas TNF-alpha, IL-6 and resistin induce insulin resistance.
2764 15953128 PAI-1 activity, fibrinogen, postload insulin and -proinsulin were significantly higher and tPA activity significantly lower in MI patients in the univariate analysis.
2765 15955127 Low plasma adiponectin levels appear to be chiefly determined by the accumulation of posterior subcutaneous abdominal fat mass, as opposed to intra-abdominal fat, and are strongly predictive of insulin resistance and dyslipidaemia.
2766 15959400 The clinical use of these PPARgamma agonists in type 2 diabetic patients leads to an improved glycemic control and an inhanced insulin sensitivity, and at least in animal models, to a protective effect on pancreatic beta-cell function.
2767 15960859 Administration of leptin during pregnancy and lactation to these protein-restricted dams produces offspring that have increased metabolic rate and do not become obese or insulin resistant when fed on a high-fat diet.
2768 15963038 Adiponectin correlated positively with insulin sensitivity (r = 0.29, p = 0.06) and negatively with first-phase insulin levels (r = -0.47, p = 0.001).
2769 15963038 In a multiple regression analysis, 48% of the variance in first-phase insulin secretion was explained by the independent effects of race (p = 0.017), adiponectin (p = 0.03), and percentage of body fat (p < 0.001).
2770 15971409 Fructose does not increase insulin and leptin or suppress ghrelin, which suggests an endocrine mechanism by which it induces a positive energy balance.
2771 15892894 Telmisartan, an antihypertensive agent with evidence of partial peroxisome proliferator-activated receptor activity-gamma (PPARgamma) activity, may improve insulin sensitivity and lipid profile in patients with metabolic syndrome.
2772 15893773 RT-PCR analysis confirmed the expression of adiponectin receptor subtypes 1 and 2 in rat beta cells and showed their expression in insulin-secreting MIN6 cells.
2773 15939809 Finally, administration of irbesartan to obese Zucker rats improved insulin sensitivity and attenuated adiponectin serum depletion.
2774 15939809 The present study demonstrates that AT2R activation and certain ARBs induce adiponectin in adipocytes, which was associated with an improvement of parameters of insulin sensitivity in vivo.
2775 15964656 Adiponectin induces insulin sensitivity and modulates inflammatory responses.
2776 15964656 We thus studied the implications of adiponectin in patients with chronic hepatitis C virus (HCV) infection inherently linked to insulin resistance.
2777 15964656 In multivariate analysis, male gender, insulin resistance, high HCV load and genotype 2 were significantly associated with a lower serum adiponectin level.
2778 15975113 This study aimed to investigate if the previously observed association between the GLUT10 Ala206Thr polymorphism and variation in fasting and oral glucose-induced serum insulin concentrations could be replicated in a large-scale population-based cohort of Danish whites.
2779 15983199 This ectopic fat, along with the deficiency in leptin signaling and perhaps other adipokines, likely contributes to insulin resistance, diabetes, and hepatic steatosis.
2780 15983210 Furthermore, whereas insulin and glucokinase expression in MetCKO islets were normal, GLUT-2 expression was decreased by approximately 50%.
2781 15983224 Glucagon-like peptide 1 (GLP-1) has been proposed to act as an incretin hormone due to its ability to enhance glucose-stimulated insulin secretion.
2782 15983224 Because GLP-1 also decelerates gastric emptying, it physiologically reduces rather than augments postprandial insulin secretory responses.
2783 15983224 Therefore, we aimed to antagonize the deceleration of gastric emptying by GLP-1 to study its effects on insulin secretion after a meal.
2784 15983224 Despite augmented rises in insulin secretion, the glucose-lowering effect of GLP-1 is markedly reduced when the deceleration of gastric emptying is antagonized, illustrating the importance of this facet of the multiple antidiabetic actions of GLP-1.
2785 15983331 Raised GGT was a significant predictor of either IGT or diabetes (odds ratio 1.62 [95% CI 1.08-2.42] top quartile vs. lower quartiles, P < 0.02) after controlling for sex, age, adiposity/fat distribution, alcohol consumption, fasting plasma insulin and proinsulin levels, and 2-h postglucose plasma glucose concentrations.
2786 15983332 This is consistent with the concept that insulin resistance may precede the development of CRP elevation in the evolution of the metabolic syndrome.
2787 15992544 Forced expression of Glut4 prior to induction of sortilin leads to rapid degradation of the transporter, whereas overexpression of sortilin increases formation of GSVs and stimulates insulin-regulated glucose uptake.
2788 15994758 Homozygous WFS1 gene mutations cause Wolfram syndrome, characterized by insulin-deficient diabetes mellitus and optic atropy.
2789 15998257 Overexpression of Nox4 also significantly reversed the inhibition of insulin-stimulated receptor tyrosine phosphorylation by PTP1B, a widely expressed PTPase implicated in the negative regulation of insulin signaling, by inhibiting its catalytic activity.
2790 15998259 Increased serine phosphorylation of IRS reduces its ability to undergo tyrosine phosphorylation and may accelerate the degradation of IRS-1, offering an attractive explanation for the molecular basis of oxidative stress-induced insulin resistance.
2791 15998260 Recently, we reported that lysophosphatidylcholine, a major bioactive product of oxidized low-density lipoprotein, and angiotensin II, a vasoactive hormone and a potent inducer of reactive oxygen species (ROS), negatively regulate insulin signaling in vascular smooth muscle cells (VSMCs).
2792 16002819 Insulin sensitivity decreased in subjects with the Thr54 allele of the FABP2 polymorphism when SFAs were replaced by MUFAs and carbohydrates.
2793 16006680 The ability of protein phosphatase 2A to change its activity in the presence of glucose and inhibitors provides clues to its role in regulating insulin secretion.
2794 16006680 Characterizing protein phosphatase 2A within the beta-cell will certainly help us in understanding the mechanisms involved in insulin secretion and provide valuable information for drug development.
2795 15886226 The latter is also dependent on stimulation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).
2796 15914522 The aim of the study was to assess the effect of insulin treatment and glycemic control on plasma VEGF levels in children with new-onset diabetes.
2797 15914522 Presence of hyperglycemia and/ or insulin deficiency in children with new-onset of diabetes is associated with plasma VEGF elevation, even at the outset of disease, and this can be mitigated by insulin therapy.
2798 15914524 Low adiponectin levels, by regulating insulin resistance and metabolic profile, may contribute to the markedly increased risk of atherosclerosis in diabetic subjects.
2799 15920035 Activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma) improves insulin sensitivity and exerts antiatherogenic effects.
2800 15928242 Resistin appears to be not the main link between obesity and insulin resistance in children and adolescents but because of its association with Tanner stage, it may be related to the maturation of children during pubertal development.
2801 15978877 It was published in 1996 for the first time that a specific DP IV inhibitor in a given dose was able to completely block glucagon-like peptide-1 (GLP-1) degradation in vivo resulting in improved insulin response accompanied, by accelerated peripheral glucose disposal.
2802 16002303 Transcription factors and coactivators, including peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 are crucial in mediating insulin resistance and accelerating vascular wall inflammation, and represent promising therapeutic targets.
2803 16007265 While the physiological role of adipose tissue in cholesterol and oxLDL metabolism remains to be established, the induction of OLR1 is a potential means by which PPARgamma ligands regulate lipid metabolism and insulin sensitivity in adipocytes.
2804 16039605 Thus, lack of insulin brain stimulation induces JNK hyperphosphorylation followed by hyperphosphorylation of tau and neurofilament, and ultrastructural cellular damage, that over time may induce decrease in cognition and learning disabilities.
2805 16039993 Wild type and PYK2(-/-) mice were fed a high-fat diet for 8 weeks to induce insulin resistance/obesity.
2806 16039993 Fasting serum leptin and insulin and blood glucose levels were significantly increased in high-fat diet fed mice irrespective of the presence of PYK2 protein.
2807 16051707 Our findings demonstrate that OGT modulates macronutrient storage and dauer formation in C. elegans, providing a unique genetic model for examining the role of O-GlcNAc in cellular signaling and insulin resistance.
2808 16054041 Complex signaling networks suggest that AMPK may prevent insulin resistance, in part by inhibiting pathways that antagonize insulin signaling.
2809 16054041 Through signaling, metabolic, and gene expression effects, AMPK enhances insulin sensitivity and fosters a metabolic milieu that may reduce the risk for obesity and type 2 diabetes.
2810 16054069 We show here that GPR40 mediates both acute and chronic effects of FFAs on insulin secretion and that GPR40 signaling is linked to impaired glucose homeostasis.
2811 16054413 To test potential effects of altered insulin sensitivity on circulating adiponectin levels, we studied patients with GH deficiency (GHD) undergoing high dose GH and IGF-I treatment in a well-defined short-term setting.
2812 16060906 IDDM children showed a negative association of their plasma ghrelin (both acylated and total) with daily insulin dosage, and the three adiposity indices (BMI, skinfold thickness and percentage fat mass).
2813 16060906 The reduction in both forms of ghrelin could be involved in the development of the body mass increase of IDDM subjects with opposite effects, either influencing insulin sensitivity or exerting a compensatory restraint of feeding.
2814 16061040 Thiazolidinedione agonists for the PPAR-g system are effective in control of insulin resistance and diabetes.
2815 16061670 Here we show for the first time in vivo that overexpression of PTEN in the Wnt-1 transgenic mice resulted in a marked decrease in the insulin-like growth factor (IGF)-I receptor levels leading to a reduced IGF-I-mediated mitogenesis.
2816 16075814 On the other hand, the uncoupling induced by UCP2 in mitochondria of pancreatic beta cells decreases ATP synthesis and impairs insulin secretion in response to glucose.
2817 16077164 Activation of the glucagon-like peptide-1 (GLP-1) receptor on pancreatic beta cells by GLP-1 and exendin-4 increases insulin secretion.
2818 16080635 It is suggested that circulating resistin levels are not associated with obesity or insulin resistance in humans.
2819 16080843 To investigate the effect of TNFalpha and leptin in obesity and insulin resistance. 84 patients of type 2 diabetes mellitus and 84 nondiabetic persons were included in this study.
2820 16080843 The synergistic effect of TNFalpha and leptin may induce insulin secretion, which in turn leads to insulin resistance.
2821 16087164 Resistin, secreted from adipocytes, causes insulin resistance in rodents.
2822 16087719 We have investigated, in isolated rat adipocytes, the changes caused by GLP-1, Ex-4 and Ex-9 compared with those provoked by insulin or glucagon, upon the activity of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB), p42/44 MAP kinases (MAPKs) and p70s6 kinase (p70s6k), and the participation of these kinases and protein kinase C (PKC) in their action upon 2-deoxy-d-glucose uptake, lipolysis and lipogenesis.
2823 16087719 In normal rat adipocytes, GLP-1 and both exendins share with insulin an increasing action upon the activity of all kinases studied (except PKB), PI3K, p44 and p42 MAPKs and possibly PKC, all being required for their stimulating effect upon glucose uptake.
2824 16087719 In cells from STZ-rats the magnitude of the above parameters was, in general, comparable to that in normal animals, with some exceptions: basal PI3K activity and lipogenesis were higher, GLP-1, Ex-4 and Ex-9 failed to modify basal lipogenesis but increased PKB activity, insulin failed to affect the activity of MAPKs and the insulin-induced glucose uptake was impaired.
2825 16091781 In contrast, no insulin-like effect was apparent in other tissues examined. 3H-2-deoxyglucose accumulation was similar in all tissues analyzed, including skeletal muscle, which is thought to be particularly sensitive to IGF-I.
2826 16091781 These data suggest that the IGF-I aptamer affects clearance of radiolabeled IGF-I from the circulation, but has no marked effects on glucose nor insulin homeostasis.
2827 16093575 Troglitazone improved insulin sensitivity (mean increase in whole body glucose uptake 23.1 +/- 10.5% (p = 0.047)) and normalised plasma concentrations of hsCRP, tPA and TNF-alpha, whereas it did not significantly change IL-6, leptin and PAI-1.
2828 16098823 ARNT expression is reduced in diabetic human islets and beta cell-specific ARNT knockout mice show the impaired glucose tolerance and abnormal insulin secretion that are characteristic of type 2 diabetes.
2829 16098828 Here we show that increased dosage of Sirt1, the mammalian Sir2 ortholog, in pancreatic beta cells improves glucose tolerance and enhances insulin secretion in response to glucose in beta cell-specific Sirt1-overexpressing (BESTO) transgenic mice.
2830 16098828 Pancreatic perfusion experiments further demonstrate that Sirt1 enhances insulin secretion in response to glucose and KCl.
2831 16098828 Microarray analyses of beta cell lines reveal that Sirt1 regulates genes involved in insulin secretion, including uncoupling protein 2 (Ucp2).
2832 16098829 Accumulating evidence indicates an important role for serine phosphorylation of IRS-1 in the regulation of insulin action.
2833 16098829 Inactivation of ROK also reduces insulin-stimulated IRS-1 tyrosine phosphorylation and PI3K activity.
2834 16098829 Mass spectrometry analysis identifies IRS-1 Ser632/635 as substrates of ROK in vitro, and mutation of these sites inhibits insulin signaling.
2835 16098836 Although adiponectin and soluble tumor necrosis factor receptor-2 may be more integrally involved in insulin resistance, the studies with these biomarkers are less extensive.
2836 16099631 Therefore, insulin, and fenofibrate through PPAR-alpha activation, enhance liver mRNAs and activities of SCD-1 and Delta5 desaturases independently and synergistically through different mechanisms.
2837 16114068 Similarly, in type 2 diabetes, the adipocyte-derived cytokines including TNF-alpha are elevated in the circulation, causing inflammation and insulin resistance.
2838 16114068 We used RINr1046-38 (RIN) insulin-producing beta-cells, which constitutively express calbindin-D(28k), to characterize the effect of TNF-alpha on apoptosis, replication, insulin release, and gene and protein expression.
2839 16123336 Western blotting confirmed a profound effect of insulin resistance and diabetes on Akt and ERK signaling in stented segments. p-ERK/p-Akt ratio in stented segments uniquely correlated with neointimal response (R2=0.888, P=0.04) in insulin-resistant and type 1 and 2 diabetic rats, but not in lean controls.
2840 16143294 Thus, aside from regulating the cellular redox, TXNIP does modulate overall gene transcription and thereby may further enhance beta-cell death and impair insulin secretion.
2841 16157299 To understand the role of adipocytokines in improving insulin sensitivity via activation of the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and -gamma (PPAR-gamma), we examined the expression of visfatin, adiponectin, and TNF-alpha in visceral fat depots of Otsuka Long-Evans Tokushima fatty (OLETF) rats from early to advanced diabetic stage (from 28 to 40 weeks of age).
2842 16168052 Combined treatments with PPAR gamma and alpha agonists may potentially improve insulin resistance and alleviate atherogenic dyslipidemia, whereas PPAR delta properties may prevent the development of overweight which typically accompanies "pure" PPAR gamma ligands.
2843 16175602 In conclusion, forced overfeeding with a high-fat diet in mice induces obesity, insulin resistance, and SH in the absence of TNF signaling or Cyp2e1 induction.
2844 16177033 Conversely, insulin (10(-11) to 10(-9) M) significantly inhibited NPY expression stimulated by DEX, and the inhibitory action of insulin was abolished in the presence of TTX.
2845 16177033 The GABAB agonist baclofen significantly inhibited NPY expression stimulated by DEX, and the inhibitory action of insulin was completely abolished in the presence of either the GABAA antagonist bicuculline or the GABAB antagonist CGP35348 (p-3-aminopropyl-p-diethoxymethyl phosphoric acid).
2846 16177033 Experiments in vivo also demonstrated that increases in GAD65 mRNA expression in the arcuate nucleus preceded decreases in the NPY mRNA expression in a fasting-refeeding paradigm and that intracerebroventricular injection of insulin increased GAD65 mRNA expression in the arcuate nucleus in fasted rats.
2847 16177033 These data suggest that insulin inhibits NPY gene expression in the arcuate nucleus through GABAergic systems.
2848 16177793 Acute insulin treatment activates phosphodiesterase 3B, reduces cAMP levels and quenches beta-adrenergic receptor signalling.
2849 16178882 Our study shows that cortisone reduces glucose uptake in diabetic myotubes and that this effect seems mediated by an increased mRNA HSD1 expression emphasizing that the local conversion of inactive to active glucocorticoids may be important in the pathogenesis of insulin resistance.
2850 16179267 GLP-1 stimulates insulin secretion, delays gastric emptying, decreases glucagon levels and reduces appetite, all resulting in a fall in plasma glucose concentrations.
2851 16179286 Plasma adiponectin is associated with insulin resistance and atherosclerosis.
2852 16179286 In type 2 diabetic patients, insulin infusion decreased plasma adiponectin from 7.74+/-2.53 mg/l to 6.76+/-2.41 mg/l after 24 h (p<0.05).
2853 16179286 It is unlikely that this response to exogenous insulin is attributable to inhibition of lipolysis, since plasma adiponectin did not decrease after acipimox.
2854 16180585 We have examined the basal and insulin-mediated phosphorylation of protein kinase B (PKB), protein kinase Czeta (PKCzeta), p70(S6k), mitogen-activated protein kinase (MAPK)/p90(rsk) pathway and the expression of IGFBP-3, -4, and -5 in mice selected for body weight gain (line C) and reduction (line L).
2855 16180585 In muscle of C-line mice, insulin stimulated the p90(rsk) activity to the same extent in both experimental groups (+22% over appropriate basal value).
2856 16180585 Insulin-mediated stimulation of p90(rsk) in muscle of L-line mice amounted to +26% and +14%, for control and diabetic mice, respectively.
2857 16181235 The present study was therefore designed to explore the hypothesis that LGH, in contrast to the standard GH dose titrated to normalize serum IGF-I levels (SGH), may have differing effects on insulin sensitivity, body composition, and cardiovascular risk markers [lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and adiponectin] in adults with severe GH deficiency.
2858 16186285 In this study, we aim to assess 1) the prevalence of hyperglycemia in incident acute coronary syndrome (ACS), 2) the effect of glycemia on the outcome, and 3) the association of plasma levels of insulin and proinsulin with ACS.
2859 16186286 In stratified analyses, this CRP-diabetes association was stronger in subjects without obesity or other risk factors related to insulin resistance and in nondrinking subjects.
2860 16186388 Serum osteocalcin concentrations were also reduced in diabetic mice (P < or = 0.001) and normalized with insulin treatment.
2861 16186396 These signaling effects are associated with impaired phosphorylation of Akt substrate 160, the most proximal step identified in the canonical insulin signaling cascade regulating GLUT4 translocation and glucose uptake.
2862 16186407 Our aim was to study the impact of genetic (heritability and polymorphisms) and nongenetic (insulin, free fatty acids, and age) factors on CAPN10 mRNA expression in skeletal muscle using two different study designs.
2863 16187315 In these offspring, increased fat mass is accompanied by glucose intolerance and insulin resistance, in conjunction with an adipose tissue specific reduction in glucose transporter 4 abundance.
2864 16188169 Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that promotes glucose homeostasis through the regulation of insulin and glucagon secretion, gastric emptying, and food intake.
2865 16189176 Since GH, in turn, acutely induces lipolysis and insulin resistance in skeletal muscle, we aimed to study the isolated and combined effects of GH, free fatty acids (FFAs) and insulin sensitivity on circulating ghrelin levels in human subjects.
2866 16191489 In the 10 female and 10 male study subjects, the mean (+/-SD) hemoglobin A1c level was 9.59 +/- 1.37% initially, and it decreased to 8.53 +/- 1.11% at 3 months and to 7.83 +/- 1.26% at 6 months after initiation of U-500 insulin therapy.
2867 16079311 We conclude that physiological glucose concentrations are suitable for the culturing of EBs, that the addition of FGF2 enhances the temporal expression of genes including POU5F1, nestin, FOXA2, ONECUT1, NEUROD1, PAX6, and insulin, and that EBs can be cultured in vitro for long periods, allowing for further examination of developmental processes.
2868 16105861 Insulin-stimulated glucose disposal in adipocytes is regulated by two separate and independent pathways, the PI3K pathway and the Cbl/TC10 pathway.
2869 16128672 Similarly, transient induction of IRS1 (3-fold) in the liver or muscle of rodents occurs following feeding or insulin injection respectively.
2870 16128672 Elucidation of the mechanism by which insulin promotes IRS1 stability will permit characterization of the importance of this novel signalling event in insulin regulation of liver and muscle function.
2871 16130009 IRS-1-associated PI3K activity was stimulated by insulin three-fold in L6 myotubes.
2872 16130009 Olanzapine inhibited insulin-stimulated IRS-1-associated PI3K activity in a dose-dependent manner.
2873 16141392 Interestingly, ablation of Vgf in ob/ob mice decreased circulating glucose and insulin levels but did not affect adiposity, whereas MC4R(-)/MC4R(-) mice that are additionally deficient in VGF have improved insulin responsiveness at 7-8 wk of age, when lean MC4R(-)/MC4R(-) mice already have impaired insulin tolerance but are not yet obese.
2874 16141392 Modulation of VGF levels and/or VGF signaling may consequently represent an alternative means to regulate circulating glucose levels and insulin sensitivity.
2875 16142801 Here, we produced a recombinant CTB fusion protein linked with autoantigen T cell epitope of insulin B chain peptide 9-23 (C19S) at levels up to 200 mg/L culture media in Brevibacillus choshinensis secretion-expression system.
2876 16143422 TNFalpha pathway activity was correlated with LDL cholesterol, steatosis, and insulin resistance, which, in turn, was correlated with the severity of liver damage.
2877 16143422 TNFalpha genotype modulates the activity of the TNFalpha pathway, influences insulin sensitivity and the severity of HCV chronic hepatitis.
2878 16150913 Interestingly, phosphorylation of IRS-1 at Tyr895 continued to increase over the 20-min period, and protein kinase B (PKB) phosphorylation at Ser473 reached a plateau by 5 min, demonstrating that different profiles of phosphorylation are involved in transmission of the insulin signal despite a constant level of insulin stimulation.
2879 16150913 In muscle from rats fed high n-6 polyunsaturated or saturated fat diets, however, there was no insulin-stimulated increase in IRS-1 Tyr612 phosphorylation and a temporal difference in PKB Ser473 phosphorylation despite no difference in IR Tyr1162/1163 phosphorylation, IRS-1 Tyr895 phosphorylation, and ERK phosphorylation.
2880 16150913 These results demonstrate that under conditions of increased insulin, similar to those used to assess insulin action in vivo, chronic high-fat feeding impairs insulin signal transduction related to glucose metabolism at the level of IRS-1 Tyr612 and PKB Ser473 and that these effects are independent of the type of fat used in the high-fat diet.
2881 16166097 In correlation with this degradation, we observed a subsequent reduction in the activation of the insulin promoter and a decrease in PDX-1-mediated gene expression, i.e. glut2 and glucokinase.
2882 16170201 Pten insufficiency increased peripheral insulin sensitivity in wild type and Irs2(-/-) mice and increased Akt and Foxo1 phosphorylation in the islets.
2883 16170201 Compared with Irs2(-/-) mice, the Irs2(-/-)::Pten(+/-) mice displayed nearly normal glucose tolerance and survived without diabetes, because normal but small islets produced sufficient insulin until the mice died of lymphoproliferative disease at 12 months age.
2884 16173046 Inhibition of adenosine kinase (AK) with 5-iodotubercidin lowers the proliferation potential of T cells to the level observed for insulin-deprived cells.
2885 16174639 Amylin correlated positively with insulin (n = 42; r = 0.67; 95% CI 0.4 to 0.81), birth weight (r = 0.22; 95% CI 0.08 to 0.36), and gestation (r = 0.18; 95% CI 0.03 to 0.32).
2886 16179348 Troglitazone increased skeletal muscle Irs-1 and phospho-Akt levels following in vivo insulin treatment, whereas AGN194204 increased hepatic Irs-2 and insulin stimulated phospho-Akt in liver.
2887 16179348 These studies demonstrate distinct molecular events lead to insulin sensitization by high affinity RXR and PPARgamma agonists.
2888 16198472 In cultured hepatocytes, insulin and a high glucose concentration induce ACS-5 mRNA.
2889 16198472 Adenoviral overexpression of a nuclear form of SREBP-1c in liver of diabetic mice or in cultured hepatocytes mimics the effect of insulin to induce ACS-5.
2890 16198472 By contrast, a dominant negative form of SREBP-1c abolishes the effect of insulin on ACS-5 expression.
2891 16205883 The present findings suggest that the -8503 G/A SNP in the promoter or the -1927 T/C SNP in intron 1 of ADIPOR1 may affect insulin sensitivity and liver fat in humans.
2892 16246524 However, differences in insulin mRNA expression among different thymi were far wider than those determined by the class I and class III insulin gene alleles and maintained a clear correlation with AIRE expression.
2893 16246524 These results confirm the effect of IDDM2 alleles on insulin expression in the thymus, but suggest that the levels of AIRE may exert a stronger influence than IDDM2 alleles themselves.
2894 16277977 The monomeric G-protein, Rhes, is a candidate imidazoline-regulated molecule involved in mediating the insulin secretory response to efaroxan [S.L.
2895 16277977 The results demonstrate that desensitization of the insulin response to efaroxan, or to another imidazoline, BL11282, does not change Rhes mRNA expression levels.
2896 16277977 Transfection of MIN6 cells with plasmids containing Rhes or Rhes-antisense also does not alter efaroxan- or BL11282-induced insulin secretion.
2897 16280646 When oxidative stress was induced in vitro in beta cells, the insulin gene promoter activity and mRNA levels were suppressed, accompanied by the reduced activity of pancreatic and duodenal homeobox factor-1 (PDX-1) (also known as IDX-1/STF-1/IPF1), an important transcription factor for the insulin gene.
2898 16282543 We previously showed that a -232C>G promoter polymorphism within a cis-acting element required for basal and cAMP-mediated PCK1 gene transcription results in loss of negative regulation by insulin, contributing to worsened metabolic control in the context of insulin resistance.
2899 16285470 It is considered that insulin sensitizers exert their benefit through indirect induction of adiponectin expression.
2900 16286515 In humans, low plasma adiponectin concentrations precede a decrease in insulin sensitivity and predict type 2 diabetes independently of obesity.
2901 16286515 Stratified by quartiles of PFAT, adiponectin did not correlate significantly with insulin sensitivity in subjects in the lowest PFAT quartile (R2 = 0.10, p = 0.13, OGTT; and R2 = 0.10, p = 0.57, clamp), whereas the association in the upper PFAT quartile was rather strong (R2 = 0.36, p < 0.0001, OGTT; and R2 = 0.48, p = 0.003, clamp).
2902 16286515 In longitudinal analyses, plasma adiponectin at baseline preceded change in insulin sensitivity in obese (n = 54, p = 0.03) but not in lean (n = 54, p = 0.68) individuals.
2903 16286652 TTR promoted glucose-induced increases in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release.
2904 16291965 Furthermore, the addition of tungstate or insulin to the mTLC-1 cell line from Leydig cell origin increased the phosphorylation states of MAP-kinase and glycogen synthase kinase-3.
2905 16293770 We investigated here whether adenovirus-mediated changes in AMP-activated protein kinase (AMPK) activity, previously shown to affect insulin secretion in vitro, might affect islet graft function in vivo.
2906 16293771 Twenty-four hours after STZ injection, the intensified OPN expression was localized towards the periphery of the islets and surrounded the remaining insulin-positive cells.
2907 16295523 The autoantigens of Type 1A diabetes may be divided into subgroups based on their tissue distributions: Beta-cell-specific antigens like insulin, insulin derivatives, and IGRP (Islet-specific Glucose-6-phosphatase catalytic subunit Related Peptide); neurendocrine antigens such as carboxypeptidase H, insulinoma-associated antigen (IA-2), glutamic acid decarboxylase (GAD65), and carboxypeptidase E; and those expressed ubiquitously like heat shock protein 60 (a putative autoantigen for type 1 diabetes).
2908 16295695 Plum thus may increase insulin sensitivity in these rats via adiponectin-related mechanisms.
2909 16301088 Usage of CSII has been demonstrated to reduce glycosylated hemoglobin levels and frequency of severe hypoglycemia, without sacrifices in safety, quality of life, or weight gain, particularly in conjunction with the use of new insulin analogs and improvements in pump technology.
2910 16306335 Given that IL-10 is a marker of regulatory function, our data are consistent with the hypothesis that higher insulin levels in the thymus promote the formation of regulatory T-cells, a proposed explanation for the protective effect of the class III alleles.
2911 16306340 In the present study, by mating C57BL/6Nci IA-2(+/-) with IA-2beta(+/-) mice, we generated double knockout mice (IA-2(-/-)/IA-2beta(-/-)) to study the effect of the combined deletion of these two proteins on insulin secretion and blood glucose levels.
2912 16306340 Taken together, our experiments show that the dense core vesicle proteins IA-2 and IA-2beta, alone or in combination, are involved in insulin secretion, but neither alone nor in combination are they required for the development of diabetes in NOD mice.
2913 16306344 Importantly, the inflammatory component in obesity and diabetes is now firmly established with the discovery of causal links between inflammatory mediators, such as tumor necrosis factor (TNF)-alpha and insulin receptor signaling and the elucidation of the underlying molecular mechanisms, such as c-Jun NH2-terminal kinase (JNK)- and inhibitor of nuclear factor-kappaB kinase-mediated transcriptional and posttranslational modifications that inhibit insulin action.
2914 16306348 Importantly, in insulin-stimulated neuronal/brain-specific insulin receptor knockout mice, cerebral insulin receptor signaling and tau phosphorylation were completely abolished.
2915 16306350 PPARalpha activation by its agonist, Wy-14,643, as well as PPARgamma activation by its agonist, rosiglitazone, markedly improved insulin sensitivity.
2916 16306352 Thus, adipose overexpression of Dgat1 gene in FVB mice leads to diet-inducible insulin resistance, which is secondary to redistribution of fat from adipose tissue to the liver in the absence of obesity.
2917 16306356 Leptin inhibits insulin secretion and preproinsulin gene expression in pancreatic beta-cells, but signal transduction pathways and molecular mechanisms underlying this effect are poorly characterized.
2918 16306360 Selective peroxisome proliferator-activated receptor (PPAR) gamma modulation is a new pharmacological approach that, based on selective receptor-cofactor interactions and target gene regulation, should result in potent insulin sensitization in the absence of PPARgamma-mediated adverse effects.
2919 16306372 Diet-induced whole-body insulin resistance was associated with increased circulating levels of resistin and leptin but unaltered adiponectin levels.
2920 16308131 In the NGT group, maternal adiponectin concentrations were significantly negatively correlated with plasma fasting insulin, fasting C-peptide, fasting C-peptide/fasting glucose ratio, 2-h glucose, triacylglycerol, and maternal body mass index and positively correlated with high-density lipoprotein cholesterol concentration.
2921 16311100 These data show that a single meal enriched with C18:1trans-fatty acids can significantly increase insulin resistance, and that in the presence of the FABP2 Thr54 allele, may contribute to increased partitioning of glucose to triacylglycerols and insulin resistance.
2922 16311102 Insulin signaling and expression of GLUT-4, FAT/CD36, and triglycerides were assessed in muscle biopsies, obtained before the clamp and after 30 minutes of hyperinsulinemia.
2923 16311104 Glucose transport, insulin receptor (IR), and IR substrate 1 (IRS1) phosphorylation, phosphatidylinositol 3'-kinase (PI3K) activity, as well as Akt-Ser473 phosphorylation have been investigated at the end of the incubation period and after a further short-term insulin stimulation.
2924 16311104 After a short-term insulin stimulation (10 nmol/L insulin for 10 minutes), IR and IRS1 tyrosine phosphorylation, PI3K activation, and Akt-Ser473 phosphorylation significantly increased (P < .01 and P < .05 for Akt) in SkMC-L but not in SkMC-H.
2925 16311104 Moreover, in the SkMC-H, insulin stimulation was associated with the inhibition of IRS1 tyrosine dephosphorylation (P < .05).
2926 16311104 In summary, continuous exposure of cultured myoblasts to high insulin levels induces a persistent up-regulation of IR, IRS1, and PI3K activity associated with the demodulation of insulin signaling.
2927 16044321 Free fatty acids (FFA) have generally been proposed to regulate pancreatic insulin release by an intracellular mechanism involving inhibition of CPT-1.
2928 16176184 Insulin inhibits GSK3 by promoting phosphorylation of a serine residue (Ser-21 in GSK3alpha, Ser-9 in GSK3beta), thereby relieving GSK3 inhibition of glycogen synthesis in muscle.
2929 16176184 Interestingly, insulin injection of wild-type mice, which activates PKB (protein kinase B) and inhibits GSK3 to a greater degree than feeding (50% versus 25%), does not repress these genes.
2930 16186174 Finally, using in vitro cellular models of amyloid precursor protein (APP)-processing and Abeta generation/clearance, we confirmed that human recombinant (hr)CTGF may increase Abeta1-40 and Abeta1-42 peptide steady-state levels, possibly through a mechanism that involves gamma-secretase activation and decreased insulin-degrading enzyme (IDE) steady-state levels in a MAP kinase (MAPK)/ phosphatidylinositol 3-kinase (PI-3K)/protein kinase-B (AKT)1-dependent manner.
2931 16198645 As well, TC-PTP has also been recently involved in insulin signaling in vitro.
2932 16204371 Mature ghrelin has been shown to stimulate eating and to participate in the regulation of insulin signaling and glucose homeostasis.
2933 16489319 Further evidence of the relationship between insulin resistance and endothelial dysfunction is the finding that asymmetric dimethylarginine, an endogenous inhibitor of the enzyme nitric oxide synthase, is increased in insulin resistant/hyperinsulinemic individuals.
2934 16492543 The effect of amylin and amylin agonists (including pramlintide) to inhibit gastric emptying was reversed by insulin-induced hypoglycemia (Gedulin and Young, 1998; Gedulin et al., 1997b,c,d; Young et al., 1996a).
2935 16493877 Resistin and TNF-alpha positively correlated with each other, insulin, HOMA, and negatively with ghrelin.
2936 16518702 High levels of IL-6 are associated with hyperglycaemia, dyslipidemia and provoke insulin resistance.
2937 16557003 The principal mediators of diabetes-associated endothelial dysfunction are (a) increases in oxidized low density lipoprotein, endothelin-1, angiotensin II, oxidative stress, and (b) decreases in the actions of insulin or growth factors in endothelial cells.
2938 16696315 As an important thrifty gene, environment factors may exerts an effect of PPAR gamma2 on glucose homeostasis and insulin resistance.
2939 16721034 The data revealed that the administration of a high dose (0.1 mg/kg body weight/day) of DEX (HDEX) attenuated insulin signaling in the cerebral cortex and hypothalamus, whereas exercise potentiated their insulin signaling along with induction of IRS2 expression.
2940 16789486 As I/D polymorphism of angiotensin converting enzyme (ACE) gene can influence the activity of RAS, it may also influence insulin resistance.
2941 16789486 In type 2 diabetic patients the I/D genotype of ACE gene is not associated with the increased insulin resistance assessed by HOMA rate and intensity of metabolic syndrome.
2942 15857517 Here we demonstrate that both insulin and IGF-I enhance TRPV1-mediated membrane currents in heterologous expression systems and cultured dorsal root ganglion neurons.
2943 16002176 In addition waist circumference, HOMA(IR) and FFA levels are associated with CRP levels, suggesting potential roles of obesity, insulin resistance and lipolysis in the development of the subclinical inflammation associated with the MS.
2944 16099819 The coactivator Bridge-1 (PSMD9) regulates the transcriptional activation of glucose-responsive enhancers in the insulin gene in a dose-dependent manner via PDZ domain-mediated interactions with E2A transcription factors.
2945 16109478 Recent studies revealed that ligand activation of PPARbeta can induce fatty acid catabolism in skeletal muscle and is associated with improved insulin sensitivity, attenuated weight gain and elevated HDL levels thus demonstrating promising potential for targeting PPARbeta for treating obesity, dyslipidemias and type 2 diabetes.
2946 16118252 HIGT partially restored suppressed leptin levels in hyperglycemic rats and increased adiponectin concentrations to supranormal levels, consistent with indicators of insulin sensitivity.
2947 16143347 In conclusion, data presented suggest that insulin might regulate neutrophil migration and generation of PGE(2) during the course of acute lung injury induced by LPS.
2948 16173921 Glucokinase acts as the pancreatic glucose sensor and plays a critical role in the regulation of insulin secretion by the beta-cell.
2949 16174656 Compared with placebo, trimetazidine induced 1) an increase in insulin-induced forearm glucose uptake and glucose oxidation accompanied by a reduction in forearm lipid oxidation and citrate release and 2) a decrease of endothelin-1 release paralleled by a significant increase in forearm cGMP release.
2950 16204328 Serum ghrelin levels had decreased (p 0.03) and leptin had increased (p 0.02), while adiponectin and insulin levels had not significantly changed at Week 4 (p 0.29 and p 0.25, respectively).
2951 16210367 Because the central administration of leptin is capable of preventing the inhibitory effects of fasting on TRH mRNA in hypophysiotropic neurons primarily through effects on the arcuate nucleus, we determined whether the continuous administration of 30 mU/d insulin or 648 microg/d glucose into the cerebrospinal fluid by osmotic minipump might also have similar effects on the hypothalamic-pituitary-thyroid axis.
2952 16210367 In contrast, whereas insulin increased proopiomelanocortin mRNA and both insulin and glucose reduced NPY mRNA in arcuate nucleus neurons, neither prevented the fasting-induced suppression in hypophysiotropic TRH mRNA or circulating thyroid hormone levels.
2953 16210367 We conclude that insulin and glucose only partially replicate the central effects of leptin and may not be essential components of the hypothalamic-pituitary-thyroid regulatory system during fasting.
2954 16234307 Our results suggest that adiponectin controls insulin sensitivity by modulating the glycogen synthetic process in human skeletal muscle.
2955 16246168 Mice devoid of the eIF2 kinase GCN2 [general control non-derepressible-2 or EIF2AK4 (eIF2alpha kinase 4)] show sensitivity to nutritional deficiencies and aberrant eating behaviours, and deletion of PEK [pancreatic eIF2alpha kinase or PERK (RNA-dependent protein kinase-like endoplasmic reticulum kinase) or EIF2AK3] leads to neonatal insulin-dependent diabetes, epiphyseal dysplasia and hepatic and renal complications.
2956 16297879 In the present work, we report for the first time the reduced expression of both endothelial nitric oxide synthase and cyclooxygenase-2 (COX-2) proteins, as well as decreased prostacyclin production, in unstimulated human endothelial cells from insulin-dependent diabetic mothers when compared to cells from non-diabetic, control subjects.
2957 16298335 Subcutaneous vaspin mRNA expression is significantly correlated with WHR, fasting plasma insulin concentration, and glucose infusion rate during steady state of an euglycemic-hyperinsulinemic clamp.
2958 16309850 Incretin hormones have trophic effects on beta cell function that can aid prevention and treatment of diabetes. cAMP is the primary mediator of these effects, and has been shown to potentiate glucose-stimulated insulin secretion, promote proper beta cells differentiation by increasing expression of the crucial transcription factor PDX-1, and prevent beta cell apoptosis. cGMP's role in beta cell function has received far less scrutiny, but there is emerging evidence that it may have a trophic impact on beta cell function analogous to that of cAMP.
2959 16341265 Although adipose tissue expression and circulating concentrations of CCL2 (also known as MCP1), a high-affinity ligand for CCR2, are elevated in obesity, the role of CCR2 in metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation associated with obesity, has not been studied.
2960 16341265 In obese mice matched for adiposity, Ccr2 deficiency reduced macrophage content and the inflammatory profile of adipose tissue, increased adiponectin expression, ameliorated hepatic steatosis, and improved systemic glucose homeostasis and insulin sensitivity.
2961 16341265 These data suggest that CCR2 influences the development of obesity and associated adipose tissue inflammation and systemic insulin resistance and plays a role in the maintenance of adipose tissue macrophages and insulin resistance once obesity and its metabolic consequences are established.
2962 16354680 These serines lie close to the Y(632)MPM motif that is implicated in the binding of p85alpha/p110alpha PI3-kinase to IRS-1 upon insulin stimulation.
2963 16354680 Phosphomimicking mutations of these serines block insulin-stimulated activation of IRS-1-associated PI3-kinase.
2964 16358360 Ten daily injections of 400 ng IL-23, starting on the first day of MLD-STZ administration led to significant and sustained hyperglycemia along with weight loss compared with controls (no IL-23), and a significant increase in the number of infiltrating cells, a lower insulin content, enhanced apoptosis, expression of IFN-gamma and IL-17 (not seen in the controls) and a significant increase in the expression of TNF-alpha and IL-18 in the pancreatic islets.
2965 16363874 Thus, there is compelling evidence that small molecule inhibitors of PTP1B may be effective in treating insulin resistance at an early stage, thereby leading to a prevention strategy for T2DM and obesity.
2966 16367888 Resistin 1 microm significantly reduced maximum insulin-stimulated 2-deoxyglucose uptake in L6 cells from 634 to 383% (relative to 100% for control, p < 0.001), and co-administration of rosiglitazone had no effect on resistin-induced insulin resistance.
2967 16367888 In the absence of insulin, however, resistin increased glucose uptake dose-dependently (e.g., 1.75-fold at 5 microm, p < 0.001) via a mitogen-activated protein kinase-dependent pathway.
2968 16367888 These results demonstrate that various glucose-lowering therapies and oleic acid reduce resistin gene expression in isolated adipocytes, and that resistin impairs insulin-stimulated glucose uptake in skeletal muscle-derived cells.
2969 16373895 The purpose of this study was to investigate 1) whether adiponectin is associated with insulin sensitivity independent of visceral adipose tissue in African-American and Caucasian youth and 2) whether adiponectin is associated with racial differences in insulin sensitivity.
2970 16373895 Adiponectin was inversely associated (P < 0.01) with visceral adipose tissue, fasting insulin, and proinsulin and was positively related (P < 0.01) to insulin sensitivity after controlling for Tanner stage and sex independent of race.
2971 16373895 Racial differences in insulin sensitivity remained significant (P < 0.01) after controlling for leptin and visceral adipose tissue but not (P > 0.05) after additional adjustment for adiponectin.
2972 16373895 Adiponectin is associated with insulin sensitivity independent of visceral adipose tissue in both African-American and Caucasian youth.
2973 16373904 Insulin, homeostasis model assessment of insulin resistance, eNOS, and leptin at follow-up were significantly reduced in the pioglitazone group compared with the control group.
2974 16374520 Hepatic insulin receptors were functional in all the mice, but insulin signaling via the Akt-FoxO1 pathway was reduced in Irs1-/- and LKO liver, and undetected in LKO::Irs1-/- liver; however, Gsk3beta phosphorylation (Ser9) and hepatic glycogen stores were nearly normal in all of the mice.
2975 16380488 In 3T3-L1 adipocytes, insulin decreased ATGL and increased adiponutrin expression in a dose- and time-dependent manner, suggesting that insulin directly mediates this nutritional regulation.
2976 16380488 These data suggest that murine ATGL but not adiponutrin contributes to net adipocyte lipolysis and that ATGL and adiponutrin are oppositely regulated by insulin both in vitro and in vivo.
2977 16380494 Combined elevations of plasma insulin and glucose levels for 24 h produced a ninefold increase in tissue factor PCA, which was associated with an increase in monocyte tissue factor protein (flow cytometry) and mRNA (RT-PCR), increases in plasma thrombin-antithrombin complexes, prothrombin fragment 1.2, factor VIII coagulant activity, and platelet CD40 ligand as well as decreases in factor VIIa, factor VII coagulant activities, and factor VII antigen.
2978 16380495 Insulin stimulated NADPH oxidase activity; this effect was abolished by a specific protein kinase C inhibitor.
2979 16380500 In conclusion, first, serum adiponectin is associated with increased insulin sensitivity, reduced abdominal fat, and high basal lipid oxidation; however, it is HMW quantity, not total or HMW-to-total adiponectin ratio, that is primarily responsible for these relationships.
2980 16399206 We review the current evidence, which suggests that hyperinsulinaemia may elevate Abeta through insulin's competition with Abeta for IDE.
2981 16399506 Further, infusion of a PI3K inhibitor into the third cerebral ventricle of STZ-DM rats prior to peripheral insulin injection attenuated insulin-induced glucose lowering by approximately 35%-40% in both acute and chronic insulin treatment paradigms.
2982 16399506 Conversely, increased PI3K signaling induced by hypothalamic overexpression of either IRS-2 or protein kinase B (PKB, a key downstream mediator of PI3K action) enhanced the glycemic response to insulin by approximately 2-fold in STZ-DM rats.
2983 15990193 These results suggest that the genetic variant of EC-SOD gene is associated with insulin resistance and the susceptibility to type 2 diabetes.
2984 16159906 Resistin (Rstn) is known as an adipocyte-specific secretory hormone that can cause insulin resistance and decrease adipocyte differentiation.
2985 16328103 Insulin modulates TNF-alpha-induced ICAM-1 expression on microvascular endothelium controlling, therefore, leukocyte adhesion and migration.
2986 16339499 Here we show in patients with type 2 diabetes mellitus (DM2) that platelets have lost responsiveness to insulin leading to increased adhesion, aggregation, and procoagulant activity on contact with collagen.
2987 16339499 Using Ser473 phosphorylation of protein kinase B as output for insulin signaling, a 2-fold increase is found in insulin-stimulated normal platelets, but in DM platelets there is no significant response.
2988 16341686 Treatment of L6 rat skeletal muscle cells with recombinant resistin (50 nmol/l, 0-24 h) reduced levels of basal and insulin-stimulated 2-deoxyglucose uptake and decreased insulin-stimulated GLUT4myc content at the cell surface, with no alteration in the production of GLUT4 or GLUT1.
2989 16341686 Insulin-stimulated oxidation of glucose via the Krebs cycle was reduced by resistin, whereas lactate production was unaltered.
2990 16341839 Glycogen synthesis correlated inversely with the activity of phosphorylase-a, irrespective of whether this was modulated by insulin, by PKB activation or by a selective phosphorylase ligand, supporting an essential role for phosphorylase inactivation in the glycogenic action of insulin in hepatocytes.
2991 16344925 The aim of the present study was to test the hypothesis that spatio-temporal changes in insulin receptor expression in trophoblasts from first trimester to the endothelium at term shift the control of insulin-dependent processes from mother to foetus.
2992 16362280 The expression of 'insulin-resistance genes' HSD11B1 and IL6 was increased by insulin in the insulin-resistant group, but insulin failed to increase HSD11B1 expression in the insulin-sensitive group.
2993 16362280 IL6 expression increased significantly more in response to insulin in the insulin-resistant than in the insulin-sensitive group.
2994 16362285 Among Pro12 homozygotes, insulin sensitivity correlated with HDL-cholesterol concentrations, and inversely correlated with blood pressure, apolipoprotein B, triglyceride and total cholesterol concentrations.
2995 16395259 In the present study, we explore the role of decreased renal function and a genetic polymorphism on the recently discovered protein resistin, apparently able to inhibit hepatic insulin action in mice.
2996 16395259 However, in a multiple regression model, resistin, as well as all the measured markers of inflammation, was only associated with insulin resistance if GFR was not taken into account.
2997 16403445 To facilitate the production of mature insulin in non-beta-cells and to safely regulate the level of transgene expression, we introduced furin-cleavable sites into the proinsulin coding region and utilized the heat shock protein 70 (Hsp70) promoter.
2998 16408445 Exercise seems to improve insulin resistance through mitochondrial function by activating AMP-activated protein kinase(AMPK) and PPARgamma coactivator-1alpha (PGC-1alpha).
2999 16410358 Consistent with these data, FXR null mice exhibited glucose intolerance and insulin insensitivity.
3000 16410358 We further demonstrate that activation of FXR in db/db mice repressed hepatic gluconeogenic genes and increased hepatic glycogen synthesis and glycogen content by a mechanism that involves enhanced insulin sensitivity.
3001 16418280 These findings strongly suggest that inhibitory effects of ghrelin on glucose-stimulated insulin secretion are at least partly due to increased expression of IA-2beta induced by ghrelin.
3002 16424109 Unlike insulin, the PI3-K inhibitor wortmannin did not reverse GE antilipolysis, and GE did not affect phosphorylation of protein kinase B (PKB).
3003 16425966 Moreover, it has been confirmed that high proinsulin concentrations stimulate amylin secretion by pancreatic beta-cells and amyloid accumulation within pancreatic islets leading to impairment of pancreatic islets secretory function.
3004 16427606 Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease.
3005 16429400 Mutations in the sterol regulatory element binding protein gene (SREBF)-1 may contribute to insulin resistance states.
3006 16041833 Glucose metabolism, insulin sensitivity, and gene expression of key adipocyte genes, including adiponectin, interleukin 6 (Il6), 11 beta-hydroxysteroid dehydrogenase (11beta Hsd), peroxisome proliferator-activated receptor gamma (Ppar gamma), forkhead box O1 (Foxo1), glucose transporter 4 (Glut4), CCAAT/enhancer binding protein (C/ebp alpha), and fatty acid synthase (Fasn) were characterized in adipocytes from epididymal and subcutaneous fat depots of 28-week-old male WOKW rats and Dark Agouti (DA) controls.
3007 16041833 The severe insulin resistance predominantly in epididymal adipose tissue of WOKW rats is associated with a 10-fold decrease in adipocyte adiponectin gene expression, decreased Ppar gamma, but increased Foxo1 gene expression compared to DA rats.
3008 16170833 TNFalpha correlated inversely with insulin secretion in pregnancy (r = -0.35, p = 0.03) and was significantly higher in the GDM group (2.62 +/- 0.3 vs 1.88 +/- 0.3 pg/mL, p = 0.01) in pregnancy.
3009 16293713 We reported previously that insulin elevated alpha-class glutathione S-transferase (GSTs) protein levels in primary cultured rat hepatocytes (Kim et al., 2003b).
3010 16293713 The present study examines the signaling pathways involved in the regulation of alpha-class GST in response to insulin in primary cultured rat hepatocytes.
3011 16293713 Protein levels of GSTA1/2 and GSTA3/5 and activity of GST toward 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD) were increased in an insulin concentration-dependent manner.
3012 16293713 Treatment of cells with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] or rapamycin, an inhibitor of mammalian target of rapamycin and ribosomal p70 S6 kinase (p70S6K) phosphorylation, or with an adenovirus containing green fluorescent protein and a dominant-negative and kinase-dead Akt, effectively inhibited the insulin-mediated increase in alpha-class GST expression and GST activity toward NBD.
3013 16293713 In contrast, PD98059 (2'-amino-3'-methoxyflavone), an inhibitor of mitogen-activated protein kinase kinase, SP600125 (1,9-pyrazoloanthrone), an inhibitor of c-Jun N-terminal kinase, SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imadazole], an inhibitor of p38 mitogen-activated protein kinase, or bisindolylmaleimide, a broad spectrum inhibitor of protein kinase C, did not inhibit the insulin-mediated increase in alpha-class GST protein levels in hepatocytes.
3014 16302015 The purpose of this study was to determine the relationships between adipocyte hormones acylation stimulating protein (ASP), adiponectin, complement C3 (C3) (ASP precursor) and insulin, C-reactive protein (CRP), lipid profiles and insulin resistance in lean vs obese type 2 diabetes subjects.
3015 16354107 IL-1, known to inhibit glucose-induced insulin secretion by stimulating inducible nitric oxide synthase expression and increased production of nitric oxide by beta-cells, also induces beta-cell death.
3016 16384854 EU: 1) blood flow was increased [area under curve 0-360 min (milliliters per 100 milliliters of tissue); 1746 +/- 208 vs. 1344 +/- 102, P = 0.001], but glucose uptake was normal [area under curve 0-360 min (micromoles per 100 milliliters of tissue); 501 +/- 114 vs. 368 +/- 48]; 2) fasting rates of lipolysis (nanomoles per minute per 100 milliliters of tissue; 329 +/- 75 vs. 89 +/- 22, P = 0.02) and nonesterified fatty acid (NEFA) release (nanomoles per minute per 100 milliliters of tissue; 841 +/- 146 vs. 316 +/- 97, P = 0.01), and plasma NEFA levels (micromoles per liter; 623 +/- 50 vs. 454 +/- 57, P = 0.03) were increased, but were all rapidly suppressed to levels similar to those in EU after the increase in plasma insulin levels after the meal; and 3) LPL was not stimulated by insulin.
3017 16389635 At the extracellular level, the angiotensin-converting enzyme controls angiotensin II synthesis but also interferes with insulin signaling through the proper regulation of angiotensin II and through the accumulation of bradykinin.
3018 16389635 Finally, by inducing the expression of the regulatory protein SOCS-3, angiotensin II may impose a late control on the insulin signal.
3019 16394088 We also examined whether visfatin is regulated by thiazolidinediones and, thus, can contribute to the ability of these agents to improve insulin sensitivity.
3020 16458527 The majority of the published literature in this field suggests that IRS1 is the major substrate leading to stimulation of glucose transport in muscle and adipose tissues, whereas in liver, IRS1 and IRS2 have complementary roles in insulin signaling and metabolism.
3021 16463046 Univariate regression analysis showed that liver fat content, intra-abdominal fat volume, plasma glucose, insulin and HOMA-IR (homeostasis model assessment of insulin resistance) correlated with VLDL(1) TG and ApoB production.
3022 16463046 We propose that the metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, increases fatty acid flux from adipose tissue to the liver and induces the accumulation of fat in the liver.
3023 16468038 It has been suggested that the gene encoding lymphotoxin-alpha (LTA) is associated with insulin resistance, and genetic association studies in the LTA region offer some support for this.
3024 16485039 These studies suggest that pharmacological inhibition of Acc1 and -2 may be a novel approach in the treatment of NAFLD and hepatic insulin resistance.
3025 16485043 We show that the mutant FoxO1 transgene prevents beta cell replication in 2 models of beta cell hyperplasia, 1 due to peripheral insulin resistance (Insulin receptor transgenic knockouts) and 1 due to ectopic local expression of IGF2 (Elastase-IGF2 transgenics), without affecting insulin secretion.
3026 16492215 Furthermore, a lower concentration of SHBG in women with gestational diabetes identifies women at increased likelihood of requiring insulin treatment.
3027 16494846 In leptin-/- obese mice Cbl expression in heart and adipose tissue was maintained, although insulin-mediated Cbl phosphorylation and subsequent TC10 activation were significantly reduced.
3028 16498408 We propose that induction of inappropriate ICER levels lead to defects in the secretory process of pancreatic beta-cells possibly contributing, in conjunction with other known deleterious effects of hyperglycemia, to defective insulin release in type 2 diabetes.
3029 16503761 They increase insulin action through several mechanisms including: stimulation of the expression of genes that increase fat oxidation and lower plasma free fatty acid levels; increased expression, synthesis and release of adiponectin; and stimulation of adipocyte differentiation resulting in more and smaller fat cells.
3030 16505218 Hence, in the pancreatic beta-cell, tomosyn negatively regulates insulin exocytosis.
3031 16505220 Furthermore, diminished levels and/or activation of PKCalpha, PKCepsilon, PKCtheta, and PKCzeta could be part of the defective signals downstream to glucose metabolism responsible for the deranged insulin secretion in the GK rat.
3032 16505226 These data suggest that changes in necdin and E2F4 expression after rosiglitazone exposure in humans are associated with altered adipocyte differentiation and may contribute to improved insulin sensitivity in humans treated with TZDs.
3033 16505232 Activation of protein kinase C (PKC) in vascular tissue is associated with endothelial dysfunction and insulin resistance.
3034 16505232 However, the effect of vascular PKC activation on insulin-stimulated endothelial nitric oxide (NO) synthase (eNOS) regulation has not been characterized in obesity-associated insulin resistance.
3035 16505232 Insulin-stimulated increases in Akt phosphorylation and cGMP concentration (a measure of NO bioavailability) after euglycemic-hyperinsulinemic clamp were blunted in the aorta of fatty compared with lean rats but were partly normalized after 2 weeks of treatment with the PKCbeta inhibitor ruboxistaurin (LY333531).
3036 16505232 In endothelial cell culture, overexpression of PKCbeta1 and -beta2, but not PKCalpha, -delta, or -zeta, decreased insulin-stimulated Akt phosphorylation and eNOS expression.
3037 16505232 In microvessels isolated from transgenic mice overexpressing PKCbeta2 only in vascular cells, Akt phosphorylation stimulated by insulin was decreased compared with wild-type mice.
3038 16505232 Thus, activation of PKCbeta in endothelial cells and vascular tissue inhibits Akt activation by insulin and VEGF, inhibits Akt-dependent eNOS regulation by insulin, and causes endothelial dysfunction in obesity-associated insulin resistance.
3039 16505233 In adipocytes, suppressor of cytokine signaling (SOCS)3 deficiency increases insulin-stimulated insulin receptor substrate (IRS)-1 and -2 phosphorylation, IRS-associated phosphatidylinositol 3 kinase activity, and insulin-stimulated glucose uptake.
3040 16505233 Moreover, SOCS3 is required for tumor necrosis factor-alpha full inhibition of insulin-stimulated IRS-1 and -2 phosphorylation, phosphatidylinositol 3 kinase activity, and glucose uptake.
3041 16505233 Whether SOCS3 also inhibits adipocyte insulin signaling in vivo and whether this action further affects systemic insulin sensitivity is not clear.
3042 16505233 Overexpression of SOCS3 in adipocytes decreases IRS1 protein levels and subsequent insulin-stimulated IRS-1 and -2 phosphorylation, decreases p85 binding to IRS-1, and leads to decreased insulin-stimulated glucose uptake in adipocytes.
3043 16505236 In this study, mice lacking both the MCH receptor-1 (MCHr1 knockout) and leptin (ob/ob) double-null mice (MCHr1 knockout ob/ob) were generated to investigate whether the obesity and/or the insulin resistance linked to the obese phenotype of ob/ob mice was attenuated by ablation of the MCHr1 gene.
3044 16505238 Exposure of INS-1 beta-cells to elevated glucose leads to reduced insulin gene transcription, and this is associated with diminished binding of pancreatic duodenal homeobox factor 1 (PDX-1) and mammalian homologue of avian MafA/l-Maf (MafA).
3045 16505238 Nicotinamide and other low-potency poly(ADP-ribose) polymerase (PARP) inhibitors were thus tested for their ability to restore insulin promoter activity.
3046 16505238 The low-potency PARP inhibitors nicotinamide, 3-aminobenzamide, or PD128763 increased expression of a human insulin reporter gene suppressed by elevated glucose.
3047 16505238 These data suggest that low-potency PARP inhibitors increase insulin biosynthesis, in part, through a mechanism involving increased MafA gene transcription.
3048 16505239 We conclude that in PCOS skeletal muscle, 1) mitogenic signaling is enhanced in vivo and in culture, 2) ERK1/2 activation inhibits association of IRS-1 with p85 via IRS-1 Ser312 phosphorylation, and 3) ERK1/2 activation may play a role in normal feedback of insulin signaling and contribute to resistance to insulin's metabolic actions in PCOS.
3049 16505244 Insulin increased phosphorylation of IRS-1 at Ser (312) but not Ser (616) in healthy subjects, with impairments noted in nondiabetic kidney and pancreas-kidney transplant recipients.
3050 16505244 In conclusion, peripheral insulin resistance in pancreas-kidney transplant recipients may arise from a negative feedback regulation of the canonical insulin-signaling cascade from excessive serine phosphorylation of IRS-1, possibly as a consequence of immunosuppressive therapy and hyperinsulinemia.
3051 16505250 Visceral ADPN mRNA expression was correlated to measures of insulin sensitivity (fasting insulin and homeostasis model assessment).
3052 16505252 Although the associations with type 2 diabetes and plasma insulin levels are marginal and their functional consequences are yet unknown, all three amino acid substitutions are located in a functionally important part of ATF6.
3053 16509812 Conversely, overexpression of the PPARalpha isoform in the muscle or heart of mice drives diminished glucose transporter gene expression and glucose uptake into those insulin target tissues.
3054 16517403 Furthermore, GLP-1, unlike GIP, potently stimulates insulin secretion and reduces blood glucose in human subjects with type 2 diabetes.
3055 16517409 We show here that ectopic expression of very low levels of uncoupling protein 1 (UCP1) in epididymal fat (Epi) reverses both insulin and leptin resistance.
3056 16517409 In contrast, UCP1 expression in Epi of leptin-receptor mutant mice did not alter food intake, though it significantly decreased blood glucose and insulin levels.
3057 16181707 These data indicate that long term activation of the GIP receptor by daily treatment with N-AcGIP(LysPAL37) improved glucose tolerance due to enhancement of pancreatic beta cell glucose responsiveness and insulin secretion.
3058 16505481 GLP-1 induces glucose-dependent insulin secretion in the pancreas, whereas glucagon stimulates gluconeogenesis and glycogenolysis in the liver.
3059 16506055 We previously demonstrated that insulin stimulates vascular endothelial growth factor (VEGF) synthesis and secretion via phosphatidylinositol-3 kinase (PI3-K) and mitogen-activated protein kinase (MAPK) pathways in vascular smooth muscle cells (VSMC) from humans and from insulin-sensitive lean Zucker fa/+ rats.
3060 16506055 As it is not known whether the effects of insulin on VEGF involve activation of hypoxia-inducible factor-1 (HIF-1), we aimed to evaluate: (1) whether insulin modulates HIF-1alpha protein synthesis and activity; (2) the insulin signalling pathways involved; and (3) the role of insulin resistance.
3061 16506055 Using aortic VSMC taken from humans and Zucker rats and cultured in normoxia, the following were evaluated: (1) dose-dependent (0.5, 1, 2 nmol/l) and time-dependent (2, 4, 6 h) effects exerted by insulin on HIF-1alpha content in both nucleus and cytosol, measured by Western blots; (2) insulin effects on HIF-1 DNA-binding activity on the VEGF gene, measured by electrophoretic mobility shift assay; and (3) involvement of the insulin signalling molecules in these insulin actions, by using the following inhibitors: LY294002 (PI3-K), PD98059 (extracellular signal regulated kinase [ERK]), SP600125 (Jun N terminal kinase [JNK]), SB203580 (p38 mitogen-activated protein kinase) and rapamycin (mammalian target of rapamycin), and by detecting the insulin signalling molecules by Western blots.
3062 16506055 In aortic VSMC from humans and Zucker fa/+ rats cultured in normoxia insulin increases the HIF-1alpha content in cytosol and nucleus via dose- and time-dependent mechanisms, and HIF-1 DNA-binding activity on the VEGF gene.
3063 16506055 The insulin-induced increase of HIF-1alpha is blunted by the translation inhibitor cycloheximide, LY294002, PD98059, SP600125 and rapamycin, but not by SB203580.
3064 16506055 It is also reduced in Zucker fa/fa rats, which present an impaired ability of insulin to induce Akt, ERK-1/2 and JNK-1/2 phosphorylation.
3065 16527823 Hormones such as catecholamines and insulin regulate triacylglycerol metabolism through reversible serine phosphorylation of perilipin A.
3066 16527823 This association was controlled by insulin and catecholamine: perilipin B was specifically depleted from the plasma membrane in response to the catecholamine isoproterenol, while insulin increased the amount of threonine phosphorylated perilipin at the plasma membrane.
3067 16527823 The reversible translocation of perilipin B to and from the plasma membrane in response to insulin and isoproterenol, respectively, suggests a specific function for perilipin B to protect newly synthesized triacylglycerol in the plasma membrane.
3068 16528573 IL-1beta-induced nitric oxide production and decreases in insulin content and secretion were reduced by GADD45beta.
3069 16549931 Human conditions of elevated interleukin-6 (IL-6) and transgenic mice overexpressing IL-6 have increased proteolytic degradation of insulin-like growth factor binding protein (IGFBP)-3.
3070 16574064 Fluorescence polarization assays using labeled insulin reveal that IDE-N has reduced affinity to insulin relative to wild type IDE.
3071 16620274 However, although thiazolidinediones lower insulin resistance and increase subcutaneous peripheral fat in Type 2 diabetes, pioglitazone treatment had little effect on either serum adiponectin, glycaemic control or the lipoatrophy.
3072 16622294 A novel approach to reverse insulin resistance involves inhibition of the stress-activated protein kinase Jun N-terminal kinase (JNK) and the protein tyrosine phosphatases (PTPs).
3073 16625816 While in rodents resistin appears to have an important role in the development of liver insulin resistance, its role in humans is less clear, and it is probably involved in the regulation of inflammatory processes rather than in insulin sensitivity.
3074 16628256 The thiazolidinediones (TZDs), which activate PPARgamma, appear to improve glycemic control primarily by increasing peripheral insulin sensitivity and reducing hepatic glucose production, thereby helping to preserve beta-cell function.
3075 16629719 Glucagon-like peptide-1 (GLP-1) or agents that bind to its receptor (exenatide, Byetta) or agents that inhibit its destruction [dipeptidyl peptidase-IV (DPP-IV) inhibitors, Vildagliptin] improve insulin secretion, delay gastric emptying, and suppress glucagon secretion while decreasing food intake without increasing hypoglycemia.
3076 16630561 Moreover, overexpression of SHB as well as culture of EBs in presence of the angiogenic growth factors PDGF or VEGF enhanced the expression of PDX-1 and/or insulin mRNA.
3077 16630561 It is concluded that SHB and angiogenic factors promote the development of cells expressing PDX-1 and insulin in EBs and that such cells can be separated by FACS.
3078 16633080 Insulin resistance is associated with endothelial dysfunction and increased production of the pro-inflammatory vasoconstrictor peptide endothelin-1 (ET-1).
3079 16633080 This study demonstrates that dual ET(A)/ET(B) receptor blockade, but not selective ET(A) blockade, enhances EDV in subjects with insulin resistance, suggesting that ET-1 is involved in the regulation of endothelial function in individuals with insulin resistance.
3080 16634839 Three months after delivery we investigated the plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen and von Willebrand factor (vWF) in 74 women with p-GDM and 20 healthy females with normal glucose tolerance during and after pregnancy, as well as the relation of fibrinolytic parameters to insulin resistance and glycaemic control.
3081 16634839 PAI-1 inversely correlated with the insulin sensitivity index (SI) but only in women with IIS (P<0.0001).
3082 16634839 Plasminogen activator inhibitor type 1 is elevated in p-GDM women with IIS and depends on plasma proinsulin and abdominal obesity.
3083 16634983 In addition to lifestyle changes, PPARgamma agonists such as thiazolidinediones are frequently beneficial and have been shown to ameliorate insulin resistance, while activation of PPARalpha (e.g. by fibrates) can lead to improvements in free fatty acid oxidation and lipid profile, and a reduction in cardiovascular events.
3084 16634986 Adiponectin is a recently described adipokine that has been recognized as a key regulator of insulin sensitivity and tissue inflammation.
3085 16634986 AdipoR2 is most highly expressed in liver, where it enhances insulin sensitivity and reduces steatosis via activation of AMPK and increased peroxisome-proliferator-activated receptor alpha ligand activity.
3086 16634987 Furthermore, we show using the specific inhibitors LY294002 and PD98059 that insulin induced increased gelatinase activity via an intracellular signalling mechanism involving phosphatidylinositol-3 kinase (PI-3K) and the extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinases (MAPKs) respectively.
3087 16634987 The appearance of protease activity at approximately 72 kDa suggested that MMP-2 activity may be induced by insulin, however, we did not detect an increase in MMP-2 expression by Western blotting.
3088 16122839 We examined if old rats were resistant to the effects of leptin on glucose stimulated insulin secretion.
3089 16122839 ICV infusion of leptin elicited a partial effect on glucose stimulated insulin secretion in the old (25.7+/-2.5 to 15.4+/-2.4 versus 24.4+/-2.4 to 19.0+/-2.0 in young versus old, respectively) suggesting that part of the leptin resistance was beyond the BBB.
3090 16038995 Endogenous insulin was significantly associated with CHD in a model controlling for gender, age, duration of diabetes, body mass index, smoking and leptin (Odds ratio 1.45 per decile, 95% confidence interval 1.11-1.90).
3091 16038995 Leptin might have a beneficial effect on CHD in type 2 diabetes, probably by counteracting the effect of insulin-like molecules or insulin resistance.
3092 16298371 Despite the major role of insulin in regulating apolipoprotein C-III (apo C-III) production, little is known about the relationship between apo C-III and insulin resistance.
3093 16325822 Moreover, multiple linear regression analysis revealed that adiponectin contributed more strongly to CRP than other factors, including the index of insulin resistance.
3094 16682803 However, insulin increased SOD activity but not its expression.
3095 16682803 In contrast to males, however, insulin does not regulate NOS in the microcirculation of diabetic females.
3096 16720654 Elevation of free fatty acid induced a condition of insulin resistance but did not affect either circulating visfatin or its mRNA.
3097 16720663 Alström syndrome (AS) is a monogenic form of infancy-onset obesity and insulin resistance, caused by ALMS1 mutations.
3098 16807405 A marked decrease of basal and insulin-stimulated AKT phosphorylation, which correlated with the increase of patients' insulin resistance, and a significant increase of IRS total protein expression, together with a lower (IRS-2) or absent (IRS-1) increase of insulin-induced tyrosine phosphorylation, were found.
3099 16814613 Improvements in liver histology during TZD therapy may be modulated by an adiponectin-mediated effect on insulin sensitivity and hepatic fatty acid metabolism rather than by changes in proinflammatory cytokines.
3100 16870142 To clarify its regulation in diabetes and metabolic syndrome, we investigated the effect of insulin on angptl4 mRNA expression in 3T3-L1 adipocytes by using quantitative real-time PCR.
3101 16870142 Insulin suppressed angptl4 mRNA expression in time- and dose-dependent manners, and the inhibitory effect was attenuated by a RNA synthesis inhibitor actinomycin D and a phosphoinositide 3-kinase (PI3K) inhibitor LY294002.
3102 16870142 In addition, insulin failed to decrease angptl4 mRNA expression in an insulin-resistant state induced by TNF-alpha in 3T3-L1 adipocytes.
3103 16873683 Perforin and granzyme B impaired insulin secretion from islet cells, and this was accompanied by cytochrome c release, caspase activation, and DNA fragmentation.
3104 16873689 Conversely, the congenic region unique to MOB5 (162-180 Mb) increased insulin resistance but had little effect on atherosclerosis and adiposity.
3105 16873694 We showed that FFAs inhibited insulin signaling and eNOS activation through different mechanisms.
3106 16873694 Palmitic acid inhibits insulin signaling by promoting PTEN activity and its transcription through p38 and its downstream transcription factor ATF-2.
3107 16873695 We previously showed that insulin has a profound effect to suppress pyruvate dehydrogenase kinase (PDK) 4 expression in rat skeletal muscle.
3108 16873695 In the present study, we examined whether insulin's effect on PDK4 expression is impaired in acute insulin-resistant states and, if so, whether this change is accompanied by decreased insulin's effects to stimulate Akt and forkhead box class O (FOXO) 1 phosphorylation.
3109 16873695 Insulin stimulation of Akt and FOXO1 phosphorylation was also significantly decreased with Intralipid and lactate infusions.
3110 16873695 These data suggest that insulin's effect to suppress PDK4 gene expression in skeletal muscle is impaired in insulin-resistant states, and this may be due to impaired insulin signaling for stimulation of Akt and FOXO1 phosphorylation.
3111 16873698 IGF-binding protein (IGFBP)-related protein 1 (IGFBP-rP1) has been shown to bind both IGFs and insulin, albeit with low affinity, and to inhibit insulin signaling.
3112 16873698 We hypothesized that IGFBP-rP1 is associated with insulin resistance and components of the IGF system in humans.
3113 16873698 Although no changes in IGF system components were evident by IGFBP-rP1 quartiles in nondiabetic subjects, independent positive associations of IGFBP-rP1 with circulating fasting IGFBP-1 were evident after adjustment for insulin resistance parameters in both nondiabetic and type 2 diabetic subjects, with IGFBP-rP1 explaining 2 and 11% of IGFBP-1 variance, respectively.
3114 16873698 These findings show for the first time that circulating IGFBP-rP1 is increased with insulin resistance, and they also suggest novel interactions between IGFBP-rP1 and the IGF system in humans.
3115 16873703 Our results suggest that PI3 kinase-dependent Akt activation, an essential signal for HSP72 expression, is depressed in the heart in insulin-resistant OLETF rats, and the results suggest also that the restoration of HSP72 expression and tolerance against ischemia/reperfusion injury by treatment with pioglitazone might be due to an improvement of insulin resistance, leading to restoration of impaired PI3 kinase-dependent Akt activation in response to hyperthermia.
3116 16873706 A number of serine kinases that phosphorylate serine residues of IRS-1 and weaken insulin signal transduction have been identified.
3117 16880400 Although PI3K enzymatic activity is diminished in L-Pik3r1KO livers because of a reduced level of regulatory and catalytic subunits of PI3K, insulin-stimulated Akt activity is actually increased.
3118 16880599 TNFalpha induces insulin resistance in type 2 diabetes, but its mechanism of action is not fully understood.
3119 16881111 Elevated levels of adiponectin in SLE, despite inverse correlation with IR, suggest the possible involvement of adiponectin in IR and alterations in its effect on insulin sensitivity.
3120 16882729 The knockout of O-GlcNAcase (oga-1) in C. elegans mimics many of the metabolic and signaling changes associated with human insulin resistance and provides a genetically amenable model of non-insulin-dependent diabetes.
3121 16883034 Vitamin D deficiency/insensitivity induces type 2 diabetes through impaired insulin secretion involving VDR on pancreatic beta cells, as well as type 1 diabetes through the reduction in immuno-modulatory action of 1,25 (OH)(2) vitamin D.
3122 16885549 The ATP-sensitive potassium (K(ATP)) channel, composed of the beta-cell proteins sulfonylurea receptor (SUR1) and inward-rectifying potassium channel subunit Kir6.2, is a key regulator of insulin release.
3123 16894402 Functions and expression of insulysin, an enzyme involved in the degradation of neurotoxic amyloid peptides and insulin, are usually impaired or reduced in Alzheimer's disease and diabetes.
3124 16624268 Serum leptin levels did not correlate significantly with HbA1c, disease duration or daily insulin dose but, correlated positively with body mass index (BMI) and fat mass (FM) in patients as in controls.
3125 16730098 Pituitary adenylate cyclase-activating peptide (PACAP) is a ubiquitous peptide of the glucagon superfamily that is involved in glucose homeostasis and regulation of insulin secretion.
3126 16730098 Feeding activity, body weight, basal plasma glucose and plasma insulin concentrations were not significantly affected by chronic PACAP(6-27) treatment.
3127 16730098 However, PACAP(6-27) treatment impaired glucose tolerance, insulin sensitivity and the glycaemic response to feeding.
3128 16766189 Reproduction of this phenotype, by mutating the same enzyme in another strain with normal glucose tolerance, suggests that the mechanism of the transhydrogenase-dependent inhibition of insulin secretion involves a partial uncoupling by the UCP2 protein.
3129 16794223 Thus, under conditions of PI3K activation by insulin, and to a lesser extent by the SR-BI ligand HDL, cell surface expression of SR-BI was promoted, resulting in increased SR-BI-mediated HDL selective lipid uptake.
3130 16897338 Variants of ENPP1 are associated with infantile arterial calcification, obesity, and insulin resistance.
3131 16903823 Not only insulin but also glucose and exercise can activate PKCzeta through diverse pathways.
3132 16912828 Insulin pump therapy is not required for all patients with type 1 diabetes, since intensive treatments produce very similar results in terms of glycated hemoglobin and control of complications over the medium and long terms.
3133 16913824 These effects of PPAR-gamma agonists appear to result from both insulin sensitization and a direct modulation of transcriptional activity in the vessel wall.
3134 16914601 The purpose of the present work was to get more insight into the regulation of adiponutrin gene expression by insulin and/or glucose using clamp studies and to examine its potential dysregulation in subjects with a deterioration of glucose homeostasis.
3135 16914601 Adiponutrin gene expression was also analyzed in patients with different levels of insulin resistance.
3136 16914601 Infusion of both insulin and glucose (HGHI) had an additive effect on the adiponutrin expression (tenfold, P = 0.008).
3137 16828971 Protein tyrosine phosphatase 1B (PTP1B) is a key element in the negative regulation of the insulin signaling pathway and may play an important role in diabetes and obesity.
3138 16857751 Despite its function in the inhibition of glucagon secretion, somatostatin fails to reduce hyperglycemia in type 2 diabetes, due to a parallel suppression of insulin secretion.
3139 16880201 This correlates with the dominant negative effect of both the AS160(T642A) and the AS160(4P) mutants on insulin-stimulated GLUT4 translocation.
3140 16880201 These data show that the insulin-dependent association of 14-3-3 with AS160 plays an important role in GLUT4 trafficking in adipocytes.
3141 16885156 The insulin-regulated forkhead box O1 (FoxO1) and steroid regulatory element-binding protein-1c (SREBP-1c) strongly inhibited hepatocyte nuclear factor 4alpha and peroxisome proliferator-activated receptor gamma coactivator-1alpha trans-activation of the CYP7A1 gene.
3142 16885156 FoxO1 binds to an insulin response element in the rat CYP7A1 promoter, which is not present in the human CYP7A1 gene.
3143 16885156 Insulin rapidly phosphorylates and inactivates FoxO1, whereas insulin induces nuclear SREBP-1c expression in human primary hepatocytes.
3144 16885156 Chromatin immunoprecipitation assay shows that insulin reduced FoxO1 and peroxisome proliferators-activated receptor gamma-coactivator-1alpha but increased SREBP-1c recruitment to CYP7A1 chromatin.
3145 16887799 Inhibition of CDK5 prevented this decrease of insulin gene expression.
3146 16887799 We used DNA binding (gel shift) assays and Western immunoblots to demonstrate that cellular levels of the transcription factor PDX-1, normally decreased by glucotoxicity, were preserved with CDK5 inhibition, as was the binding of PDX-1 to the insulin promoter.
3147 16916991 The metabolic effects of adiponectin, including insulin sensitivity, seem to become stronger with increasing adiposity.
3148 16934249 Furthermore, pGL3.hINS-363 3x shows significant promoter activity in differentiated AR42J cells that can produce insulin after activin A and betacellulin treatment.
3149 16968152 These nestin-positive cell-derived ICCs expressed numerous beta-cell lineage genes, including insulin; Glut-2; pancreatic duodenal homebox-1 protein (PDX-1); islet amyloid polypeptide (IAPP); neurogenin 3 (ngn3); and alpha, gamma, and delta cell gene markers.
3150 16979397 These findings suggest that BDNF prevents exhaustion of the pancreas in diabetic mice by maintaining the histologic cellular organization of beta cells and non-beta cells in pancreatic islets and restoring the level of insulin-secreting granules in beta cells.
3151 16981139 Activation of PARP by ROS may be an important mediator of vascular dysfunction in insulin resistance.
3152 16981720 However, this response was independent of IR-PTK activity because in cells overexpressing a PTK-inactive form of IR, insulin response was attenuated while the effect of BMOV remained intact.
3153 16984235 Seven days treatment with IGF-I/IGFBP-3 complex enhanced overnight insulin sensitivity and reduced GH levels, but there was no effect on glomerular hyperfiltration or albumin excretion rates.
3154 16995414 Incretin effect of glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1) is significantly involved in the insulin secretion which is modulated by many other hormones.
3155 16998828 Intensive research in these fields, combined with mouse models, is reviewed with respect to the molecular control of muscle growth (myogenesis) and atrophy/hypertrophy and fat deposition (adipogenesis) in skeletal muscle, with a focus on IGF-1/insulin signaling.
3156 17000240 Analyses that used PathwayAssist (Ariadne Genomics, Rockville, MD) revealed a number of potential signaling pathways and genes involved in insulin signaling and stress response (insulin 2, insulin-binding protein 1, GST pi1), cell growth (GAP43, CSF1R, HGF), calcium signaling (calbindin 3, CBP A6), and PKC signaling (PKCBP beta15, FABP5), in concert with prior biochemical and molecular findings.
3157 17002473 We also showed that dietary CLA significantly decreased the level of tumor necrosis factor-alpha (TNF-alpha), associated with the development of insulin resistance, in the skeletal muscle of Zucker rats.
3158 17003289 This study examined the effects of glucagon-like peptide-1 (GLP-1) on insulin secretion alone and in combination with sulphonylureas or nateglinide, with particular attention to K(ATP) channel-independent insulin secretion.
3159 17003289 In depolarised cells, GLP-1 significantly augmented glucose-induced K(ATP) channel-independent insulin secretion in a glucose concentration-dependent manner.
3160 17003289 In contrast, GLP-1 exhibited a reduced but still significant insulin-releasing effect following PKA and PKC downregulation, indicating that GLP-1 can modulate K(ATP) channel-independent insulin secretion by protein kinase-dependent and -independent mechanisms.
3161 17003289 The synergistic insulin-releasing effects of combinatorial GLP-1 and sulphonylurea/nateglinide were lost following PKA- or PKC-desensitisation, despite GLP-1 retaining an insulin-releasing effect, demonstrating that GLP-1 can induce insulin release under conditions where sulphonylureas and nateglinide are no longer effective.
3162 17003306 Insulin sensitivity increased approximately 40% during high insulin clamp after pioglitazone (P < 0.01) and remained unchanged in the Plc group (P < 0.05 PIO vs.
3163 17003306 Plasma adiponectin increased after pioglitazone (P < 0.001) and correlated with delta FPG (r = -0.54, P < 0.03), delta GNG flux (r = -0.47, P < 0.05), and delta insulin sensitivity (r = 0.65, P < 0.005).
3164 17003330 Here, we demonstrate that when expressed on a hyperphagic ob/ob background, the P465L PPARgamma mutant grossly exacerbates the insulin resistance and metabolic disturbances associated with leptin deficiency, yet reduces whole-body adiposity and adipocyte size.
3165 17003331 An increase in bradykinin has been suggested to contribute to the enhanced insulin sensitivity observed in the presence of ACE inhibitors.
3166 17003331 In contrast, insulin-stimulated extracellular signal-regulated kinase1/2 and Jun NH2-terminal kinase (JNK) activation were decreased in the presence of bradykinin, accompanied by decreased IRS-1 Ser307 phosphorylation.
3167 17003331 Furthermore, bradykinin did not enhance insulin action in the presence of the JNK inhibitor, SP-600125, or in adipocytes from JNK1-/- mice.
3168 17003331 These data indicate that bradykinin enhances insulin sensitivity in adipocytes via an NO-dependent pathway that acts by modulating the feedback inhibition of insulin signaling at the level of IRS-1.
3169 17003332 Although interleukin-6 (IL-6) has been associated with insulin resistance, little is known regarding the effects of IL-6 on insulin sensitivity in humans in vivo.
3170 17003332 Because skeletal muscle accounts for most of the insulin-stimulated glucose disposal in vivo, we examined the mechanism(s) by which IL-6 may affect muscle metabolism using L6 myotubes.
3171 17003332 IL-6 treatment increased fatty acid oxidation, basal and insulin-stimulated glucose uptake, and translocation of GLUT4 to the plasma membrane.
3172 17003332 Our results demonstrate that acute IL-6 treatment enhances insulin-stimulated glucose disposal in humans in vivo, while the effects of IL-6 on glucose and fatty acid metabolism in vitro appear to be mediated by AMPK.
3173 17003334 To assess the role of STAT5 activity in beta-cells in vivo, we generated transgenic mice that expressed a dominant-negative mutant of STAT5a (DNSTAT5) or constitutive active mutant of STAT5b (CASTAT5) under control of the rat insulin 1 promoter (RIP).
3174 17003335 A similarly bimodal induction of FLIP, pancreatic duodenal homeobox (PDX)-1, and Pax4 mRNA expression, as well as glucose-stimulated insulin secretion, was observed.
3175 17003336 The integrin-dependent adhesion of fetal beta-cells to both collagen IV and vitronectin induces significant glucose-independent insulin secretion and a substantial reciprocal decline in insulin content.
3176 17003336 Using real-time PCR, we demonstrate that adhesion of both fetal and adult beta-cells to collagen IV and vitronectin also results in the marked suppression of insulin gene transcription.
3177 17003344 As there is a paucity of IGF-I receptors in the liver and as the IGF-IGFBP system in the central nervous system is emerging as physiologically relevant, we examined whether the effects of IGF-I and IGFBP-3 on insulin action are mediated through central mechanisms.
3178 17003344 Marked, opposing, and independent physiological effects of IGF-I and IGFBP-3 through central mechanisms may have implications on potential strategies in specific modulation of peripheral insulin action.
3179 17003345 Thus, our findings suggest that in addition to ameliorating insulin resistance, TZDs may enhance AMPK-stimulated glucose clearance into peripheral tissues in insulin-resistant states.
3180 17003352 These findings implicate several factors in the insulin signaling pathway, which may be further dysregulated in HIV+IGT, and support the notion that insulin signaling pathways for glucose and leucine metabolism may be disrupted by increased proinflammatory adipocytokines (IL-8) and increased lipid oxidation.
3181 17003355 We hypothesized that visfatin is associated with insulin secretion in humans.
3182 17003355 In nondiabetic subjects, circulating visfatin (enzyme immunoassay) was independently associated with insulin secretion (acute insulin response to glucose [AIRg] from intravenous glucose tolerance tests) but not with insulin sensitivity (Si) or other metabolic or anthropometric parameters, and AIRg alone explained 8% of visfatin variance (beta = -0.29, P = 0.001).
3183 16514419 Inhibition of EGF and LIF signalling by pharmacological antagonists of the JAK2/STAT3 pathway, or knockdown of Ngn3 by RNA interference prevented the generation of new insulin-positive cells.
3184 16621111 Glucagon-like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that augments glucose induced insulin secretion, and has a trophic effect on beta-cells.
3185 16676355 Recent studies on the role of caveolin-1 in adipocytes showed that caveolin has emerged as an important regulatory element in insulin signaling but little is known on its role in skeletal muscle cells.
3186 16778068 Insulin-deficient rats (streptozotocin, 50 mg/kg) were used to examine the effects of leptin on glucose homeostasis independent of changes in insulin.
3187 16343040 Leptin and adiponectin, two adipocytokines, may work together in regulating energy homeostasis and insulin action.
3188 16572494 Secretion of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was detected by ELISPOT after stimulation with glutamic acid decarboxylase (GAD(65), protein and aa 247-279), recombinant tyrosinphosphatase (IA-2), insulin, ovalbumin and phytohaemagglutinin (PHA).
3189 16803864 Here, we report that SHP(-/-) mice exhibited hypoinsulinemia with age, which was associated with increased peripheral insulin sensitivity and increased response of isolated islets to glucose stimulation, yet maintain normal levels of blood glucose.
3190 16803864 SHP(-/-) hepatocytes showed markedly decreased basal glucose production in cultures, and SHP(-/-) livers had increased glycogen stores and were more sensitive to insulin inhibition of glucose output, which were concomitant with decreased expression for PPARgamma1, fatty acid translocase, glucose-6-phosphatase, and phosphoenol/pyruvate carboxykinase, and increased mRNAs for glucokinase and pyruvate kinase.
3191 16803864 In white fat, SHP deficiency resulted in up-regulation of genes involved in insulin sensitizing, including PPARgamma2 and adiponectin.
3192 16803864 The results suggest that the increases in insulin sensitivity through multiple signaling pathways in muscle, liver, and fat, with an increase in islet secretory function, represent the complex mechanism whereby SHP deficiency leads to improvement in insulin sensitivity, secretion, and diabetes.
3193 16803868 APS (adaptor protein with PH and SH2 domains) initiates a phosphatidylinositol 3-kinase-independent pathway involved in insulin-stimulated glucose transport.
3194 16803868 Expression of an APS mutant unable to bind Enigma increased the insulin-induced Glut 4 translocation to the plasma membrane.
3195 16803868 Using time-lapse fluorescent microscopy of green fluorescent protein-actin, we demonstrated that the overexpression of Enigma altered insulin-induced actin rearrangements, whereas the expression of Enigma without its LIM domains was without effect.
3196 16828931 These results suggest that insulin stimulates the release of ANP through PI 3-kinase and tyrosine kinase, and augmentation of insulin-stimulated ANP release in diabetic rat atria may be partly due to an upregulation of insulin receptor.
3197 16842857 SHIP2 negatively regulates insulin signaling relatively specifically via its 5'-phosphatase activity.
3198 16842857 Importantly, inhibition of endogenous SHIP2 through the liver-specific expression of a dominant-negative SHIP2 improves glucose metabolism and insulin resistance in diabetic db/db mice.
3199 16842857 Overexpression of PTEN and SKIP also inhibited insulin-induced phosphorylation of Akt and the uptake of glucose in cultured cells.
3200 16842857 Taken together, inhibition of endogenous SHIP2 in the whole body appears to be effective at improving the insulin resistance associated with type 2 diabetes and/or obesity.
3201 16842857 Inhibition of PTEN in the tissues specifically targeted, including skeletal muscle and fat, may result in an amelioration of insulin resistance in type 2 diabetes, although caution against the formation of tumors is needed.
3202 16857181 Serum EC-SOD concentrations may be a sensitive biochemical marker of insulin resistance in patients with type 2 diabetes and hypertension and that losartan improves insulin sensitivity by increasing EC-SOD and adiponectin production and decreasing TNF-alpha production.
3203 16887936 Because PPARgamma plays a crucial role in regulation of insulin sensitivity, synthetic agonists are already in clinical use for type II diabetes treatment.
3204 16966378 These results demonstrate that skeletal muscle LKB1 is a negative regulator of insulin sensitivity and glucose homeostasis.
3205 16969645 Changes in GGT level were correlated with changes in markers of insulin resistance (fasting insulin, homeostasis model assessment of insulin resistance), as well as with the following elements of the metabolic syndrome: central obesity, and increased fasting glucose, triglycerides and blood pressure (systolic and diastolic).
3206 17010638 In the case of leptin, current evidence suggests that SOCS3 appears to be of particular importance in the development of leptin resistance, whereas the ability to diminish insulin action has been described for several SOCS proteins (SOCS1, SOCS3, SOCS6 and SOCS7).
3207 17045646 Together, these findings suggest that low circulating levels of PYY could contribute to hyperinsulinemia and insulin resistance, and possibly contribute to subsequent development of obesity and type 2 diabetes.
3208 17048191 The result suggests that plasma resistin has a role in linking central obesity and obesity-related insulin resistance to type II diabetes mellitus.
3209 17049056 Insulin secretion decreased on POD 3 in association with a significant increase of HIF-1alpha-related beta-cell death, which can be suppressed by short-term hyperbaric oxygen therapy.
3210 17050683 In the latter, palmitic acid treatment inhibits glucose-induced insulin gene transcription, in part, by interfering with autocrine insulin signaling through phosphorylation of insulin-receptor substrates 1 and 2 at sites that interfere with binding to activated insulin receptors.
3211 17052194 GPR40, activated by medium and long-chain fatty acids, has been shown to potentiate insulin secretion at the beta-cell, and has been hypothesized to participate in the detrimental effects of chronic fatty acid exposure on beta-cell function.
3212 17052202 In ob/ob mice, induction of UCP2 at age 5 weeks precedes development of insulin secretion defects and hyperglycaemia.
3213 17065333 In spite of normal pancreatic insulin content and beta-cell mass, mice with beta-cell-reduced VEGF-A expression had impaired glucose-stimulated insulin secretion.
3214 17065333 Factors modulating VEGF-A expression may influence islet vascularity and, consequently, the amount of insulin delivered into the systemic circulation.
3215 17065342 In visceral adipose tissue, CB(1) mRNA expression was negatively correlated with visceral fat mass (r = 0.32, P = 0.01), fasting insulin (r = 0.48, P < 0.001), and circulating 2-AG (r = 0.5, P < 0.001), whereas FAAH gene expression was negatively correlated with visceral fat mass (r = 0.39, P = 0.01) and circulating 2-AG (r = 0.77, P < 0.001).
3216 17065344 To identify additional epitopes, HLA class I peptide affinity algorithms were used to identify a panel of peptides derived from the beta-cell proteins islet amyloid polypeptide (IAPP), islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), insulin, insulinoma-associated antigen 2 (IA-2), and phogrin that were predicted to bind HLA-A*0201.
3217 17065346 Nevertheless, resistin deficiency improved glucose tolerance and insulin sensitivity in these severely obese mice, largely by enhancing insulin-mediated glucose disposal in muscle and adipose tissue.
3218 17065358 Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) is an inhibitor of insulin-induced activation of the insulin receptor.
3219 17065361 We conclude that the TCF7L2 T at-risk allele variation (rs7903146) predicts hyperglycemia incidence in a general French population, possibly through a deleterious effect on insulin secretion.
3220 17065388 These results show that mPTTG exhibits properties consistent with a murine securin in insulin-secreting mouse cells and mPTTG overexpression inhibits cell proliferation, suggesting that defective beta-cell proliferation observed in PTTG-/- mice is likely due to abnormal cell-cycle progression.
3221 17065392 GLP-1(9-36)amide also had no effect on plasma glucose homeostasis or insulin secretion.
3222 17066144 Functions and expression of insulysin, an enzyme involved in the degradation of neurotoxic amyloid peptides and insulin, are usually impaired or reduced in Alzheimer's disease and diabetes.
3223 17070195 Association of single-nucleotide polymorphisms from HSD17B6 in subjects with PCOS with key phenotypes of PCOS: androgen status, insulin resistance, and body mass index.
3224 16517145 Gene expression profiling using microarray and real-time PCR show significant changes in the expression of four genes--Vamp2, Dok1, Glut4 and Mapk14--involved in insulin signaling.
3225 16814919 Albumin undergoes structural and functional alterations, caused by increased glycosylation during non insulin-dependent diabetes mellitus, which is closely linked with the early occurrence of vascular complications.
3226 16822955 Although beta-cell-related gene expression (PDX-1, proinsulin I, GLUT2, glucokinase, amylin) and function (insulin content and secretion) are slightly reduced during p8 overexpression, removal of IPTG reverses beta-cell function within 24 h to normal levels.
3227 16855220 Corroborating these results, constitutively active Akt upregulated the signaling molecules involved in insulin-induced relaxation such as iNOS, cGK1alpha, and MBP activity, even in the absence of insulin stimulation.
3228 16855220 In conclusion, we demonstrated here that insulin-induced VSMC relaxation is dependent on Akt activation via iNOS, cGK1alpha, and MBP activation, as well as the decreased phosphorylations of MYPT1 and MLC20 and decreased ROKalpha activity.
3229 16912128 Measurements included plasma DPP-4 activity; post-OGTT glucose excursion; active and total incretin GIP levels; insulin, C-peptide, and glucagon concentrations; and sitagliptin pharmacokinetics.
3230 16926246 The link between adiponectin levels and a strong marker of inflammation, CRP, is independent of insulin resistance and adiposity in obese children and adolescents.
3231 16962683 Thus, the efficacy of increased leptin afferent signaling in the hypothalamus to persistently restrain pancreatic insulin release and insulin resistance can be explored as an adjunct therapeutic modality to alleviate pathophysiological derrangements that confer type 2 diabetes.
3232 16980436 The glucose sensor enzyme glucokinase plays a pivotal role in the regulation of glucose-induced insulin secretion in pancreatic beta-cells.
3233 17019595 Insulin activation of (1) IRS1, (2) IRS2, (3) phosphotyrosine-associated phosphatidylinositol-3 kinase activity and (4) the substrate of phosphorylated Akt, AS160, a functional Rab GTPase activating protein important for GLUT4 (now known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) translocation, was unchanged after acute or chronic exercise in either group.
3234 17021921 We conclude that PEA15 overexpression represents a common defect in FDR of patients with type 2 diabetes and is correlated with reduced insulin sensitivity in these individuals.
3235 17022998 Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters.
3236 17028898 Insulin-stimulated glucose transport in muscle is impaired in obesity and type 2 diabetes, but alterations in levels of relevant signalling factors, i.e. atypical protein kinase C (aPKC) and protein kinase B (PKB/Akt), are still uncertain.
3237 17028898 The aim of this study was to test the hypothesis that dose-related effects of insulin may account for the reported differences in insulin signalling to PKB in diabetic muscle.
3238 17028898 We compared enzymatic activation of aPKC and PKB, and PKB phosphorylation (threonine-308 and serine-473) during hyperinsulinaemic-euglycaemic clamp studies using both submaximal (400-500 pmol/l) and maximal (1400 pmol/l) insulin levels in non-diabetic control and obese diabetic subjects.
3239 17028898 In lean control subjects, the submaximal insulin concentration increased aPKC activity and glucose disposal to approximately 50% of the maximal level and PKBbeta activity to 25% of the maximal level, but PKBalpha activity was not increased.
3240 17028898 In these subjects, phosphorylation of PKBalpha and PKBbeta was increased to near-maximal levels at submaximal insulin concentrations.
3241 17028898 In obese diabetic subjects, whereas aPKC activation was defective at submaximal and maximal insulin concentrations, PKBbeta activation and the phosphorylation of PKBbeta and PKBalpha were defective at submaximal, but not maximal, insulin concentrations.
3242 17033837 This study provides in vitro and in vivo evidence that common variants in the MODY3 gene, HNF-1alpha, influence transcriptional activity and insulin secretion in vivo.
3243 17072583 TNFalpha has been described as a link between obesity and the development of insulin resistance, an important contributor to the pathogenesis of type 2 diabetes.
3244 17083157 Tumor necrosis factor-alpha (TNF-alpha) system is potentially involved in the development of insulin resistance during pregnancy.
3245 17083620 The function of secretagogin is unknown, but it has been suggested in beta-cells to influence calcium-influx, insulin secretion and proliferation, and has been observed downregulated in diabetes-prone BB rat islets exposed to cytokines.
3246 17084707 ATM seemingly does this by inhibiting JNK, a stress kinase involved in inflammation with related effects in insulin resistance and atherosclerosis.
3247 17084707 In an interesting twist, the authors show that chloroquine, an antimalarial drug, also activates ATM, which inhibits JNK, and improves insulin sensitivity and cardiovascular effects.
3248 17086934 In the beta-cell, cAMP is formed by the activity of adenylyl cyclase, especially in response to the incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic peptide. cAMP may also play a similar role in regulating GLP-1 secretion from intestinal L-cells. cAMP influences many steps involved in glucose-induced insulin secretion and may be important in regulating pancreatic islet beta-cell differentiation, growth and survival. cAMP itself is rapidly degraded in the pancreatic islet beta-cell by cyclic nucleotide phosphodiesterase enzymes.
3249 17087783 The decrease in TNF-alpha concentrations during oGTT and the inverse correlation between endogenous hyperinsulinaemia and serum TNF-alpha concentrations suggested an anti-inflammatory effect of moderately-high insulin concentrations.
3250 17088412 To examine adiponutrin regulation by the insulin pathway in relation to other WAT-related proteins with well-known relation to insulin signaling and action, we examined in healthy young men (1) the association of adiponutrin with p85alpha PI3K and HKII, leptin, adiponectin, and acylation-stimulating protein (ASP) and (2) the regulation of adiponutrin and WAT-derived proteins by 3-h hyperinsulinemic euglycemic clamp (HIEG).
3251 17088412 In healthy young men, adiponutrin expression is upregulated [corrected] by hyperinsulinemia and is related to basal and/or insulin-stimulated p85alpha PI3K, HKII, adiponectin, and leptin expression levels.
3252 17088412 We hypothesize that insulin-mediated regulation of adiponutrin expression is under the PI3K pathway.
3253 17088580 Among patients with type 1 or type 2 diabetes, there was a small decrease in hemoglobin A1c level from baseline that favored subcutaneous insulin over inhaled insulin (weighted mean difference, 0.08% [95% CI, 0.03% to 0.14%]), although there was no difference in the proportion of participants achieving hemoglobin A1c levels less than 7%.
3254 17100762 A low IFN-gamma response to insulin was found in type 1 diabetic children, whereas allergic children responded to insulin by increased IL-4 secretion.
3255 17109620 Insulin stimulated glutamate-L-cysteine ligase (GCL) activity by activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling, increased serine phosphorylation and nuclear translocation of nuclear NF-E2-related factor 2 (Nrf2), and upregulation of Nrf2-dependent GCL-catalytic (GCLc) subunit expression.
3256 17109620 Inhibitors of insulin receptor tyrosine kinase, PI3K, Akt and mTOR abrogated insulin-induced Nrf2-mediated GCLc expression, redox balance, and IHEC survival.
3257 16960399 Adiponectin, a novel anti-atherosclerotic and anti-inflammatory adipose tissue product, which is closely associated with insulin resistance, was reported to be low in smokers with cofactors for atherosclerosis.
3258 16854579 We propose that in the liver, the mitogen-activated protein kinase, c-jun N-terminal kinase (JNK), links excessive nutrient metabolism with impaired insulin regulation of glucose production.
3259 16930851 Adipocyte generated endocrine signals, including leptin and adiponectin, control systemic insulin sensitivity as part of a broader control mechanism in energy balance.
3260 16962100 Acetaldehyde suppressed basal and insulin-stimulated Akt phosphorylation without affecting total Akt expression.
3261 17038556 By targeting IRS-1, IL-1beta is capable of impairing insulin signaling and action, and could thus participate in concert with other cytokines, in the development of insulin resistance in adipocytes.
3262 17053028 In this study, we demonstrate that diazoxide prevents the onset and development of diabetes in OLETF rats by inhibiting beta-cell apoptosis via increasing p38beta MAPK, elevating Bcl-2/Bax ratio, and ameliorating insulin secretory capacity and action.
3263 17084991 These data suggest that D. opposita has insulin sensitivity that is associated with the regulation of GLUT4 expression.
3264 17101212 We investigated a potential role for GPR40 in the generation of the FFA-induced Ca2+ signal and insulin secretion.
3265 17101212 Downregulation of GPR40 by specific siRNA treatment lead to a significant inhibition of the FFA-induced [Ca2+]i response and insulin secretion, indicating that the FFA-stimulated Ca2+ signal and insulin secretion involve activation of GPR40 in pancreatic beta-cells.
3266 17127239 Future studies are necessary to determine whether IRS2 dysfunction may promote atherosclerosis in normoglycemic, pre-diabetic patients with clinical manifestations of hyperinsulinemia and insulin resistance.
3267 17127455 Type 1 Diabetes (T1D) is an autoimmune disease requiring contributions from effectors in both CD4+ and CD8+ T cell compartments in order to destroy insulin producing pancreatic beta cells.
3268 17140783 In addition, oral administration of cinnamaldehyde (20 mg/kg bw) significantly decreased glycosylated hemoglobin (HbA(1C)), serum total cholesterol, triglyceride levels and at the same time markedly increased plasma insulin, hepatic glycogen and high-density lipoprotein-cholesterol levels.
3269 17179929 In obesity and insulin resistance, increased secretion of proinflammatory cytokines and decreased secretion of adiponectin from adipose tissue, increased circulating levels of free fatty acids, and postprandial hyperglycemia can all alter gene expression and cell signaling in vascular endothelium, cause vascular insulin resistance, and change the release of endothelium-derived factors.
3270 16960657 We have already shown that chronic exposure to the ketone body beta-hydroxybutyrate (OHB) decreases insulin-mediated activation of protein kinase B (PKB) and glucose uptake in cardiomyocytes.
3271 16960657 Furthermore, this treatment decreased by 54 and 36% the phosphorylation of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-K) and PKB in response to insulin, whereas it did not alter vanadate-mediated activation of these enzymes.
3272 17014924 The inflammatory response to hyperglycemia and insulin resistance could be the major factors for the increased expression of TGF-beta1.
3273 17035298 Incubation of INS 832/13 cell lysates with polyphosphoinositides (e.g., PIP(2)), phosphatidic acid, phosphatidylcholine, and phosphatidylserine significantly promoted trafficking of cytosolic Rac1 to the membrane fraction.
3274 17090752 Conclusions: insulin therapy improves hepatic insulin sensitivity and slightly but significantly reduces liver fat content, independent of serum adiponectin.
3275 17106060 Similar to insulin, ghrelin acutely stimulated increased production of NO in bovine aortic endothelial cells (BAEC) in primary culture (assessed using NO-specific fluorescent dye 4,5-diaminofluorescein) in a time- and dose-dependent manner.
3276 17106060 However, unlike insulin, ghrelin did not stimulate MAP kinase-dependent secretion of the vasoconstrictor endothelin-1 from BAEC.
3277 17212361 Glucose and insulin-induced ERK 1/2 phosphorylation also stimulated connective tissue growth factor gene expression.
3278 17213476 TZD administration for sufficient duration to improve insulin action and increase adiponectin levels did not affect expression of AdipoR1 or AdipoR2.
3279 17218436 We gave insulin intravenously to these rats and determined the association of glucose transporter-4 with plasma membranes, as well as the phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1), Akt, and PKCzeta.
3280 17218436 Insulin stimulation of PDK1, Akt, and PKCzeta phosphorylation was also reduced.
3281 17230448 Depletion of E2F1-3 was sufficient for inducers such as insulin to potently induce PAI-1 gene expression in pre-adipocytes.
3282 17259477 Retinol-binding protein 4 (RBP4) is an adipokine that induced insulin resistance in mice, and high plasma RBP4 levels were associated with insulin-resistant states in humans.
3283 17259477 Adjusted circulating RBP4 correlated negatively with insulin sensitivity (clamp: r = -0.33, P = 0.005; OGTT: r = -0.36, P = 0.002) and positively with parameters in the fasting state as insulin levels (r = 0.35, P = 0.003) and homeostasis model assessment of insulin resistance (r = 0.34, P = 0.004).
3284 17259477 In addition, circulating RBP4 correlated negatively with hepatic insulin clearance (r = -0.25, P = 0.04).
3285 17264162 Insulin activates the glucokinase gene from plasma membrane-standing IR-B, while c-fos gene activation is dependent on clathrin-mediated IR-B-endocytosis and signaling from early endosomes.
3286 17287461 A higher glucokinase enzyme activity accompanied by an improved glucose-induced insulin secretion indicated the integration of ECFP-glucokinase into the functional pool of glucokinase protein in MIN6-ECFP-glucokinase cells.
3287 17287461 Interestingly, glucokinase was also colocalized with kinesin, a motor protein involved in insulin secretory granule movement.
3288 17287471 ARHGEF11, which encodes the Rho guanine nucleotide exchange factor 11, was analyzed as a positional candidate gene for this linkage because this protein may stimulate Rho-dependent signals, such as the insulin signaling cascade.
3289 17287471 These findings suggest that variation within ARHGEF11 nominally increases risk of type 2 diabetes, possibly as a result of increased insulin resistance.
3290 17303803 These data demonstrate that deletion of Trib3 has minimal effect on insulin-induced Akt activation in hepatic tissue, and, as such, they question any nonredundant role for Trb3 in the maintenance of glucose and energy homeostasis in mice.
3291 17303804 Among these molecules, adiponectin has drawn much attention because of its insulin-sensitizing and antiatherogenic actions, suggesting that genetic deficits in its production or action may contribute to insulin resistance and coronary artery disease (CAD).
3292 17317761 We conclude that variation in TCF7L2 is associated with GDM and interacts with adiposity to alter insulin secretion in Mexican Americans.
3293 17322479 Further adjustment for insulin resistance made minor differences to the IL-6 diabetes relationship (adjusted RR 2.12 [1.18-3.81]), weakened the associations with adiponectin (0.59 [0.33-1.04]), and abolished the association between leptin and diabetes (1.12 [0.55-2.26]).
3294 17322479 By contrast, the positive association between IL-6 and diabetes appeared to be independent of obesity and insulin resistance.
3295 17353063 In addition, serum GGT was correlated significantly (r=0.266, p<0.001 in men and r=0.264, p<0.001 in women) with homeostasis model assessment of insulin resistance (HOMA-IR).
3296 17363743 In cardiomyocytes, PKC inhibition attenuated fatty acid-induced increases in the metabolic genes PDK4 and UCP3 and also prevented fatty acid-mediated inhibition of basal and insulin-stimulated glucose oxidation.
3297 17369523 Rho guanine nucleotide exchange factor 11 (ARHGEF11), located on chromosome 1q21, is involved in G protein signaling and is a pathway known to play a role in both insulin secretion and action.
3298 17372717 Leptin, an adipocyte-secreted hormone, plays an important role in regulating neuroendocrine and immune function as well as insulin resistance and metabolism.
3299 17383157 Ectopic PDX-1 expression induced pancreatic gene expression and insulin production in the mice livers.
3300 17390150 The recent observations that Peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1A) is responsible for the induction of reactive oxygen species (ROS) detoxifying agents and that ROS triggers insulin resistance, support the role that this gene could play in the onset of Type 2 diabetes mellitus (T2DM).
3301 17407387 We assessed the in utero and neonatal role of two key regulators of pancreatic insulin secretion by studying birthweight and the incidence of neonatal hypoglycaemia in patients with heterozygous mutations in the maturity-onset diabetes of the young (MODY) genes HNF4A (encoding HNF-4alpha) and HNF1A/TCF1 (encoding HNF-1alpha), and the effect of pancreatic deletion of Hnf4a on foetal and neonatal insulin secretion in mice.
3302 17408806 This restorative effect of insulin was abolished by a K+ channel blocker (tetraethylammonium), by nitric oxide synthase inhibitor (N-nitro-L-arginine methyl ester) and by a cyclooxygenase inhibitor (indomethacin).
3303 17437080 IGT or IFG) in a cross-sectional study (Study II); and (3) insulin secretion, insulin sensitivity and adipose tissue expression of TCF7L2 in offspring of type 2 diabetic probands (III).
3304 17445799 Here, we investigate the role of Hepatocyte growth factor-Regulated tyrosine kinase Substrate (Hrs), a regulator of RTK trafficking, in VEGF and insulin signaling.
3305 17457565 After transplantation, the PDX1-positive cells further differentiated into mature cell types producing insulin and glucagon, resulting in amelioration of hyperglycaemia and weight loss in streptozotocin-treated diabetic mice.
3306 17464184 However, in the presence of insulin, t-RVT also potentiated the effect of insulin on glucose uptake via AMPK activation, which led to further activation of PI-3 kinase/Akt signal pathway.
3307 17465332 From an analysis of the actions of IL-6 and of additional literature, we postulate that skeletal muscle also secretes an unidentified hormone, which we have named Musculin (Latin: musculus = muscle), which acts on the pancreatic beta-cell to restrain the size of the (beta-cell mass and to tonically inhibit insulin secretion and biosynthesis.
3308 17465332 It is suggested that the amount of Musculin secreted is determined by, and is positively correlated with, the prevailing insulin sensitivity of skeletal muscle, thereby accounting for the hyperinsulinemia that occurs in insulin resistant disorders such as type 2 diabetes mellitus, obesity, and the polycystic ovary syndrome.
3309 17465724 GPR40, which is preferentially expressed in pancreatic beta-cells, mediates the majority of the effects of FFAs on insulin secretion.
3310 17469039 At a molecular level, insulin resistance involves defects of insulin signalling such as reduced insulin receptor tyrosine kinase activity and reduced post-receptor phosphorylation steps that impinge on metabolic and vascular effects of insulin.
3311 17472010 Endocrinal products of adipocytes (PPARgamma, A-FABP, E-FABP, leptin, adiponectin and others) modulate insulin tissue sensitivity enabling them to participate in the ethiopathogenesis of diabetes mellitus type 2 (DM2T).
3312 17473455 Therefore, irrespective of the structural changes in pancreatic beta-cells due to STZ, HJ increased insulin production and secretion by the pancreas and significantly suppressed GLUT2 synthesis in the liver.
3313 17479443 The aim of this study was to evaluate the impact of insulin sensitivity on the association between TSH and PRL in euthyroid obese subjects.
3314 17479443 The insulin sensitivity and carbohydrate homeostasis seem to be involved in relationship with PRL and TSH by the brain via serotoninergic and dopaminergic system.
3315 17484887 Reduction in hepatic ADRP level using an antisense oligonucleotide reverses hepatic steatosis, hypertriglyceridemia, and insulin resistance in obese mice, suggesting that ADRP may be targeted for the treatment of NAFLD and associated lipid and glucose abnormalities.
3316 16787648 Using logistic regression analysis we demonstrated that IL-6 levels (III versus I tertile, OR: 2.10; 1.10-3.75), TG (III versus I tertile OR: 27.45; 8.47-88.93), fasting insulin (III versus I tertile OR: 2.84; 1.50-5.42), and age (OR: 1.038; 1.002-1.075) were associated with low HDL-C independent of smoking, BMI, waist circumference, hypertension, diabetes, physical activity, alcohol intake, oral hypoglycaemics, CRP, IL-18, and TNF-alpha levels.
3317 16988889 Both an increased workload and the hormone insulin induce translocation of FAT/CD36 and GLUT4 to the sarcolemma.
3318 17208384 Adipocyte-derived hormones, including adiponectin and leptin, regulate systemic insulin sensitivity in accordance to existing triglyceride reserves.
3319 17208384 Leptin levels reflect existing fat mass and the adipokine negatively regulates insulin action in adipose tissue.
3320 17208384 Finally, after delineating critical nodes of insulin and adipokine crosstalk, putative pathways are proposed by which adiponectin and leptin cooperatively regulate systemic insulin sensitivity in accordance to existing fat mass.
3321 17208384 Adiponectin-mediated increments of AMPK activity, on the other hand, may attenuate mTOR signaling, leading to the preservation of insulin sensitivity in periods of increased nutrient availability.
3322 17289847 Unlike receptors for GLP-1 and other peptides that mediate enhanced glucose-dependent insulin release, GPR119 was suitable for the development of potent, orally active, small-molecule agonists.
3323 17289847 The GPR119-specific agonist AR231453 significantly increased cAMP accumulation and insulin release in both HIT-T15 cells and rodent islets.
3324 17289847 AR231453 also enhanced glucose-dependent insulin release in vivo and improved oral glucose tolerance in wild-type mice but not in GPR119-deficient mice.
3325 17299398 In this study, we genetically engineered an enteroendocrine cell line (STC-1) to express insulin under the control of the glucose-dependent insulinotropic polypeptide promoter.
3326 17347312 Our results suggest that decreased plasma adiponectin, increased plasma resistin and cholesterol, and elevated levels of TNF-alpha and IL-6 in adipocytes may all contribute to the insulin resistance observed in GH-Tg mice.
3327 17376428 Finally, these direct adipotropic endocrine effects of atorvastatin were paralleled by the acute inhibition of insulin-induced glucose uptake in differentiated white adipocytes, while protein expression of the thermogenic uncoupling protein-1 (UCP-1) in brown adipocytes remained unchanged.
3328 17376833 We hypothesized that critical genetic susceptibility loci that control progression to T1D, designated as insulin-dependent diabetes (Idd) loci, would be responsible for preventing CD8 T cell tolerance.
3329 17376836 We have used an inducible diabetes model based on rat insulin promotor (RIP)-driven expression of CD80 (B7-1) on pancreatic beta cells.
3330 17389595 Ad-GPAT1-treated rats had 50% lower hepatic NF-kappaB activity and no difference in expression of tumor necrosis factor-alpha and interleukin-beta, consistent with hepatic insulin resistance in the absence of increased hepatic inflammation.
3331 17403669 Consistent with these data, treatment of MIN6 cells with O-(2-acetamido-2-deoxy-d-glucopyranosylidene)-amino N-phenylcarbamate, an inhibitor of O-GlcNAcase, causes Neuro-D1 localization to the nucleus and induction of insulin gene expression even on low glucose.
3332 17416680 Although both groups on the high-fat diet developed insulin resistance, beta IRKO, but not beta IGFRKO, mice exhibited poor islet growth consistent with insulin-stimulated phosphorylation, nuclear exclusion of FoxO1, and reduced expression of Pdx-1.
3333 17416903 Although overnight exposure to high insulin, glucose, glucosamine, or amino acids had no effect, saturated fatty acids potently reduced PGC-1alpha and -beta mRNA expression.
3334 17426391 In addition, insulin-stimulated translocation of hippocampal GLUT4 to the plasma membrane was completely abolished in CORT-treated rats.
3335 17444618 They bind and activate the pancreatic GLP-1 receptor (GLP-1R) with similar affinity and potency and thereby promote insulin secretion in a glucose-dependent manner.
3336 17467667 These results suggest that elevated concentrations of PA commonly present in obese and insulin resistant individuals can increase NF-kappaB-mediated expression of IP-10 in macrophages.
3337 17487263 This project assesses the treatment role with insulin and (or) angiotensin II receptor subtype-1 (AT1-R) blocker (ARB) on insulin receptor and endothelin-1 receptor subtype (ETA-R and ETB-R) regulation in rat hearts suffering from insulin-dependent diabetes mellitus (IDDM).
3338 17487263 However, ETB-R expression was significantly reduced in the diabetic group treated with both insulin and an ARB.
3339 17487263 The changes in the expression of the insulin, the ETA-Rs, and the ETB-Rs at the various sites of the myocardium and the effect of both insulin treatment and blockade of the AT1-R explain the new benefits related to the halting of myocardial remodeling in IDDM rats.
3340 17495595 PAI-1 may play several roles in contributing to obesity: through indirect effects on insulin signalling, by influencing adipocyte differentiation and by regulating recruitment of inflammatory cells within adipose tissue.
3341 17504187 We caution that despite the convincing associations between the activation of AMPK signalling and the restoration of insulin sensitivity, future studies in genetic models of AMPK deficiency or constitutive activation within skeletal muscle are needed to evaluate the quantitative role of AMPK and to validate whether strategies designed to activate skeletal muscle AMPK may be important for regulating whole-body insulin sensitivity.
3342 17505151 Suppressor of cytokine-3 (SOCS-3) has been proposed as a possible mediator of insulin-induced leptin resistance.
3343 17508912 Losartan selectively inhibited oxidative stress via downregulation of NADPH oxidase; this in turn suppressed UCP2 expression, thus improving beta-cell insulin secretion and decreasing apoptosis-induced beta-cell mass loss in db/db mouse islets.
3344 17512313 MMP-9 correlated with body mass index (BMI) (r = 0.33, P = .005) and fasting insulin (r = 0.3, P = .013); TIMP-1 correlated with BMI (r = 0.35, P = .006).
3345 17512313 In the group of obese hypertensive children (n = 25), MMP-9 correlated with BMI (r = 0.41, P = .001), systolic blood pressure (r = 0.41, P = .002), fasting insulin (r = 0.37, P = .006), and homeostasis model assessment index of insulin resistance (r = 0.27, P = .03).
3346 17264850 After adjustment for these factors, adiponectin was significantly inversely associated with insulin resistance, triglyceride, C-reactive protein (but not interleukin 6), tissue plasminogen activator and alanine aminotransferase and positively associated with high-density lipoprotein cholesterol (HDL-cholesterol) and Factor VIII, factors associated with diabetes.
3347 17325688 Baseline leptin correlated positively with anthropometric measurements, fasting and postload insulin and homeostasis model assessment indices (all P<0.001), and inversely with subsequent weight increase.
3348 17337902 The aim of our study was to investigate the effects of GHT on glucose and insulin homeostasis in PWS children.
3349 17384344 Changes in fat deposition were associated with decreased postprandial mRNA adiponectin levels in peripheral adipose tissue and lower insulin sensitivity index values from a frequently sampled insulin-assisted intravenous glucose tolerance test in patients fed a CHO-rich diet compared with a MUFA-rich diet (ANOVA P < 0.05).
3350 17395251 NS treatment (alone or in combination with hPTH) significantly increased the area of insulin immunoreactive beta-cells in diabetic rats; however, hPTH treatment alone only led to a slightly increase in the insulin-immunoreactivity.
3351 17400930 Provision of exogenous H2O2 scavengers, including cell permeable catalase and N-acetyl-L-cysteine, inhibited glucose-stimulated H2O2 accumulation and insulin secretion (GSIS).
3352 17416795 Circulating RBP4 was not associated with age, BMI, waist-to-hip ratio, or metabolic parameters, including insulin sensitivity (r = -0.03, P = 0.6).
3353 17416795 On the contrary, circulating RBP4 was negatively associated with insulin secretion, especially in obese subjects (r = -0.48, P = 0.007), in whom RBP4 also was linked to insulin disposition index (r = -0.44, P = 0.01).
3354 17416796 Incretin (gastric inhibitory peptide [GIP] and glucagon-like peptide-1 [GLP-1]) levels and their effect on insulin secretion were measured before and 1 month after RY-GBP in eight obese women with type 2 diabetes and in seven obese nondiabetic control subjects.
3355 17416797 Our findings suggest that the TCF7L2 risk allele may predispose to type 2 diabetes by impairing beta-cell proinsulin processing.
3356 17416798 Activation of c-Jun NH2-terminal kinase (JNK) inhibits insulin signaling in cultured cells and in vivo and thereby promotes insulin resistance.
3357 17426289 SorCS1 is the gene identified as responsible for the mouse chromosome 19 T2dm2 quantitative trait locus for fasting insulin levels, acting via impaired insulin secretion and increased islet disruption in obese females.
3358 17429060 The objective of the present analysis was to evaluate the association of alanine aminotransferase (ALT) with directly measured insulin sensitivity (S(i)) in a large, multiethnic cohort of U.S. adults and to determine whether ALT adds to existing metabolic risk definitions in identifying subjects with insulin resistance.
3359 17440021 The aim was to investigate the association between RBP4 and various markers related to insulin resistance and diabetic complications in type 2 diabetic patients.
3360 17440021 The current study shows that RBP4 is associated with variables related to insulin resistance and diabetic complications.
3361 17440173 Fatty acid inhibition of basal and insulin-stimulated leptin release is linked to CD36-facilitated fatty acid flux, which is important for fatty acid activation of peroxisome proliferator-activated receptor gamma and likely contributes to the nutrient sensing function of adipocytes.
3362 17456851 FFA-induced inhibition of insulin secretion was not associated with increased transcript levels of the apoptosis markers Bax (BclII-associated X protein) and caspase-3.
3363 17459944 In addition, insulin treatment promoted the formation of large, elongate ASM cells, characterized by dramatic accumulation of contractile phenotype marker proteins and phosphorylated p70(S6K) (downstream target of PI 3-kinase associated with ASM maturation).
3364 17495860 We suggest that strict metabolic control and reversing insulin resistance in patients with diabetes may blunt the process of amylin deposition in the kidney and possibly protect renal function in these patients.
3365 17515919 Conversely, disruption of Mcp1 or its receptor Ccr2 impairs migration of macrophages into adipose tissue, thereby lowering adipose tissue inflammation and improving insulin sensitivity.
3366 17516074 Mechanism analysis indicated that the effect of insulin and 2-BP on the FAT/CD36 mRNA gene expression may be mediated through activation of PPAR-gamma, suggesting that FAT/CD36 may have important implications in the pathophysiology of defective fatty acid metabolism.
3367 17555594 TRX activity was assayed by the insulin disulfide reducing assay.
3368 17571165 Insulin resistance in these tissues was associated with reduced insulin-stimulated insulin receptor substrate 1- (IRS-1-) and IRS-2-associated PI3K activity in muscle and liver, respectively.
3369 17579828 This study suggests that young carriers of a PGC-1beta 203Pro allele have enhanced insulin-stimulated glucose metabolism and may be protected against an age-related decline in PGC-1beta expression in muscle.
3370 17579832 TCF7L2 expression was not altered by genotype and did not correlate with insulin sensitivity or BMI.
3371 17579832 We confirmed TCF7L2 as a risk factor in a population of European descent, where it reduced glucose tolerance and insulin sensitivity, but not insulin secretion.
3372 17583797 In the present study the effect of these cytokines and mitogen-activated protein kinase kinase kinase 1 (MEKK1), which is known to be activated by these cytokines, on human insulin gene (INS) transcription was investigated.
3373 17583797 IL-1beta and MEKK1 specifically inhibited basal and membrane depolarisation and cAMP-induced INS transcription in the beta cell line.
3374 17583797 Also, in primary islets of reporter gene mice, IL-1beta reduced glucose-stimulated INS transcription.
3375 17583797 These data suggest that IL-1beta through MEKK1 inhibits INS transcription and does so, at least in part, by decreasing MafA transcriptional activity at the RIPE3b control element.
3376 17583797 Since inappropriate insulin biosynthesis contributes to beta cell dysfunction, inhibition of MEKK1 might decelerate or prevent progression from a prediabetic state to diabetes mellitus.
3377 17592026 Ghrelin was colocalized with insulin in ss-cells in LBW group.
3378 17592243 In addition, IL-1alpha and TNF-alpha stimulating the insulin, TGF-beta, and Toll-like receptor signaling pathways may have different effects in diabetic keratocytes.
3379 17592437 Mutations in the IPF1 gene cause MODY4; IPF1 D76N is a polymorphism, which inhibits the insulin promoter and decreases insulin-secretion.
3380 17596883 Associations between biomarkers of nonalcoholic fatty liver disease (NAFLD) alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), with 3 separate measures of glucose homeostasis: fasting glucose, fasting insulin and glycated hemoglobin (HbA1c) were studied and compared between women with and without diabetes in order to gain insight into the documented associations between NAFLD, insulin resistance and diabetes.
3381 17596883 GGT is associated with fasting insulin (and HOMA) to the same extent in all women, irrespective of diabetes status.
3382 17609509 The objectives of this study were to determine if heparanase is induced by high glucose in endothelial cells and if heparin and/or insulin or basic fibroblast growth factor (bFGF) affect this upregulation.
3383 17618943 In a multivariable analysis, high-density lipoprotein cholesterol concentration was positively associated and male sex and insulin concentration were negatively associated with plasma adiponectin concentration.
3384 17475934 Adiponectin increases insulin sensitivity and contributes to insulin's indirect effects on hepatic glucose production.
3385 17475934 These data provide evidence for a mechanism of adiponectin resistance and corroborate the notion that adiponectin potentiates hepatic insulin sensitivity.
3386 17491019 This study examines HADHSC expression in purified rat beta cells and investigates whether its selective suppression elevates insulin release.
3387 17513702 Interestingly, training improved insulin action on thigh blood flow, and, furthermore, in both basal and insulin-stimulated muscle tissue, activities of Akt1 and GS and phosphorylation of AS160 increased with training (all P < 0.05).
3388 17513703 It appears likely that ESR1 contributes to type 2 diabetes and CVD risk via pleiotropic effects, leading to insulin resistance, a poor lipid profile, and obesity.
3389 17519423 Because it is activated by lipopolysaccharide and saturated fatty acids, which are inducers of insulin resistance, TLR4 may be a candidate for participation in the cross-talk between inflammatory and metabolic signals.
3390 17526931 Because Dgat catalyzes triglyceride synthesis from diacylglycerol, and because we have hypothesized that diacylglycerol accumulation triggers fat-induced hepatic insulin resistance through protein kinase C epsilon activation, we next sought to understand the paradoxical reduction in diacylglycerol in Dgat2 ASO-treated rats.
3391 17533199 Angiotensin II, acting through its angiotensin type 1 receptor, inhibits the actions of insulin in the vasculature which may lead to deleterious effects such as vascular inflammation, remodeling, endothelial dysfunction, and insulin resistance.
3392 17533199 Further, there was reduced insulin induced Akt activation and increased tumor necrosis factor-alpha levels in vascular smooth muscle cells from Ren2 and Sprague-Dawley rats treated with angiotensin II, abnormalities that were abrogated by angiotensin type 1 receptor blockade with valsartan or antioxidant N-acetylcysteine.
3393 17536066 Overexpression of Ubc9 resulted in an inhibition of GLUT4 degradation and promoted its targeting to the unique insulin-responsive GLUT4 storage compartment (GSC), leading to an increase in GLUT4 amount and insulin-responsive glucose transport in 3T3-L1 adipocytes.
3394 17536066 Overexpression of Ubc9 also antagonized GLUT4 downregulation and its selective loss in GSC induced by long-term insulin stimulation.
3395 17536066 By contrast, siRNA-mediated depletion of Ubc9 accelerated GLUT4 degradation and decreased the amount of the transporter, concurrent with its selective loss in GSC, which resulted in attenuated insulin-responsive glucose transport.
3396 17536066 Thus, Ubc9 is a pivotal regulator of the insulin sensitivity of glucose transport in adipocytes.
3397 17548353 The widely expressed Sec/Munc18 (SM) protein Munc18c is required for SNARE-mediated insulin granule exocytosis from islet beta cells and GLUT4 vesicle exocytosis in skeletal muscle and adipocytes.
3398 17550900 We applied RNA interference to investigate the specific role of hepatic JNK1 in contributing to insulin resistance in DIO mice.
3399 17572128 As skeletal muscle is the principal site of the peripheral insulin resistance for glucose disposal in type 2 diabetes, we investigated whether targeted suppression of calpain-10 expression directly affects insulin action in cultured human skeletal muscle cells.
3400 17572128 Suppression of CAPN10 mRNA expression (75% decrease compared to untransfected myotubes) was associated with a significant decrease (p=0.04) in insulin-stimulated glucose uptake (1.03+/-0.06 [mean+/-SEM]-fold increase over basal) compared to the untransfected myotubes (1.43+/-0.16-fold increase).
3401 17606264 Therefore, we suggest that the functional interactions between ALP and PC-1 may link insulin resistance to vascular calcification.
3402 17631765 TP with insulin stimulation in normal pregnancy group was lower than that in normal nonpregnant group (0.85 +/- 0.09; P<0.01). (4) Protein expression and TP with insulin stimulation of IRS-1 was negatively related to HOMA-IR in GDM group (r=- 0.613, -0.632; P<0.01), and TP with insulin stimulation was negatively related to HOMA-IR in normal pregnancy group (r=-0.526, P<0.05).
3403 17640481 In vivo-transduced NeuroD in the small intestine remained functionally active and could ameliorate the non-fasting glucose levels of streptozotocin-induced, diabetic mice by inducing enteric insulin expression.
3404 17646722 The total percentage of daily insulin doses delivered as basal rates was similar in both groups and was negatively associated (beta=-2.956, p=0.05) with glycosylated hemoglobin (HbA1c) values.
3405 17650802 SJG can lower blood glucose and inhibit ET-1 and PKC expressions to improve vascular endothelial function, thus to promote insulin sensitiveness and alleviate IR.
3406 17318810 The adipocyte derived peptide hormone leptin is known to regulate apoptosis and cell viability in several cells and tissues, as well as having several pancreatic islet beta-cell specific effects such as inhibition of glucose-stimulated insulin secretion.
3407 17429733 ET-1 is also a mediator that is elevated in conditions such as insulin resistance, hyperglycemia, oxidative stress, and endothelial cell dysfunction.
3408 17475936 BMI, abdominal adiposity, systolic blood pressure, and triglycerides increased and adiponectin and HDL decreased significantly (P for trend for all <0.05), with decreasing insulin sensitivity in both races.
3409 17557929 Inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) is a negative regulator of insulin signalling and has previously been found to be associated with hypertension, obesity and type 2 diabetes in a cohort of families with diabetes in the UK presenting features of metabolic syndrome.
3410 17603034 In this study, we determined the in vitro effect of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation on the aortic relaxation, lipolysis and insulin-induced [(3)H]-glucose uptake of the abdominal (omental) adipocytes of the non-diabetic (+db/+m) and obese/diabetic (+db/+db) mice.
3411 17603034 In contrast, none of the PPAR-gamma agonists tested (0.1, 1 and 10 microM) altered the basal and the insulin (0.1 microM)-induced [(3)H]-glucose uptake into adipocytes of both species.
3412 17603034 However, all PPAR-gamma agonists examined have no acute effect on lipolysis and the insulin-induced glucose uptake into adipocytes of both +db/+m and +db/+db mice.
3413 17609256 Therefore, we determined insulin clearance in response to endogenously secreted and exogenously administered GIP and GLP-1.
3414 17609256 The endogenous secretion of GIP or GLP-1 was unrelated to the changes in insulin clearance.
3415 17609256 Likewise, infusing GLP-1 during a meal course did not alter insulin clearance (P = 0.87).
3416 17609256 Neither GIP nor GLP-1 has significant effects on insulin extraction.
3417 17629673 Indeed, it now appears that insulin specifically regulates the docking and/or fusion of GLUT4-vesicles with the plasma membrane.
3418 17629673 Future work will focus on identifying the key insulin targets that regulate the GLUT4 docking/fusion processes.
3419 17640984 Phosphorylation of some serine/threonine residues in IRS-1 dampens insulin signaling, whereas phosphorylation of other serine/threonine residues enhances insulin signaling.
3420 17640984 Cells expressing the Ser(629)Ala mutation, along with increased Ser(636) phosphorylation, had decreased insulin-stimulated association of the p85 regulatory subunit of phosphatidylinositol 3'-kinase with IRS-1 and decreased phosphorylation of Akt at Ser(473).
3421 17644513 By metabolic labeling, we here identify phosphatidylinositol 3-phosphate as the sole in vivo product of the insulin-dependent activation of PI3K-C2alpha, confirming the emerging role of such a phosphoinositide in signaling.
3422 17644513 We also demonstrate that PI3K-C2alpha contributes to maximal insulin-induced translocation of the glucose transporter GLUT4 to the plasma membrane and subsequent glucose uptake, definitely assessing the role of this enzyme in insulin signaling.
3423 17687539 In 24 Ab+ relatives sampled fasted, adiponectin levels correlated significantly with homeostasis model assessment of insulin sensitivity (p = 0.006).
3424 17705360 Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways and thus an attractive therapeutic target for diabetes and obesity.
3425 17719095 Adipose tissue macrophages (ATMs) are suspected to be the major source of inflammatory mediators such as TNF-alpha and IL-6 that interfere with adipocyte function by inhibiting insulin action.
3426 17725654 IA-2 also is an intrinsic transmembrane component of dense core secretory vesicles and knock-out studies showed that IA-2 is a regulator of insulin secretion.
3427 17784830 By day 34, Pdx1+ cells comprise between 5% and 20% of the total cell population and Insulin gene expression is up-regulated, with release of C-peptide into the culture medium.
3428 17786204 By genotyping of 921 metabolically characterized German subjects for the reported candidate single nucleotide polymorphisms (SNPs), we show that the major alleles of the SLC30A8 SNP rs13266634 and the HHEX SNP rs7923837 associate with reduced insulin secretion stimulated by orally or intravenously administered glucose, but not with insulin resistance.
3429 17786204 The HHEX and SLC30A8 genes encode for proteins that were shown to be required for organogenesis of the ventral pancreas and for insulin maturation/storage, respectively.
3430 17510498 FoxO1 is expressed in a subset of pancreatic duct cells, in which insulin and/or Pdx1 are occasionally expressed.
3431 17575366 Here we report the rare case of acromegaly that presents inappropriately normal IGF-1 levels at the time of diagnosis in uncontrolled type 2 diabetic patient and shows increased IGF-1 levels after glycemic control with insulin therapy.
3432 17578889 Moreover, in depolarized islets incubated with 2.8 mM glucose, activation of protein kinase C or protein kinase A potentiated insulin release; however, under these conditions, resveratrol was ineffective.
3433 17606872 Following preliminary studies that indicated that a peripheral intravenous insulin dose of 0.1 mU x kg(-1) x min(-1) (lower than those used previously) provides basal insulin replacement and that a glucagon dose of 1.0 ng x kg(-1) x min(-1) underreplaces basal glucagon, we infused the somatostatin analog octreotide (30 ng x kg(-1) x min(-1)) (with growth hormone replacement) over 4 h in 14 healthy adults on four separate occasions to produce endogenous insulin and glucagon deficiency with 1) saline (combined insulin and glucagon deficiency), 2) insulin replacement (isolated glucagon deficiency), 3) partial glucagon replacement (insulin and partial glucagon deficiency), and 4) insulin and partial glucagon replacement (partial glucagon deficiency).
3434 17609417 LRP-1 expression on the hepatic plasma membrane was increased in a time-dependent manner by portal infusion of insulin and was 2.2-fold greater than that in nontreated controls after a 10-min infusion, whereas the expression in whole lysate was not affected by insulin treatment.
3435 17609417 The apparent hepatic uptake of [(125)I]Abeta(1-40) was also induced by insulin in a time-dependent manner.
3436 17609417 In conclusion, plasma insulin facilitates LRP-1 translocation to the hepatic plasma membrane from the intracellular pool, resulting in significant enhancement of hepatic Abeta(1-40) uptake from the circulating blood.
3437 17622585 In this study, we provide evidence in rats that low-dose alcohol intake (4 g/kg x d) enhances hepatic insulin signaling by suppressing p55gamma (a phosphatidylinositol 3-kinase regulatory subunit isoform) at the posttranscriptional level, leading to the increased association of the phosphatidylinositol 3-kinase catalytic subunit (p110) with insulin receptor substrate-1 (P < 0.05) and subsequent activation of downstream effectors such as Akt, glycogen synthase kinase 3beta, and nuclear sterol regulatory element binding protein (SREBP)-1.
3438 17622585 These results, combined with our previous data (confirmed in the present study) demonstrating that ethanol intake at high doses (13 g/kg x d) disrupts hepatic insulin signaling by inducing TRB3, a mammalian homolog of Drosophila (tribbles-related protein 3) that prevented activation of downstream effectors (such as Akt, GSK3beta, and nSREBP-1), provide clear mechanistic validation of the biphasic effects of ethanol on insulin signaling.
3439 17622585 Thus, alcohol exerts biphasic actions on hepatic insulin signaling, such that low doses activate insulin signaling pathways associated with reduced p55gamma to increase nSREBP-1, whereas high doses of ethanol elevate TRB3 and suppress insulin signaling to decrease SREBP-1.
3440 17630267 Retinol-binding protein (RBP)-4 was recently identified as an adipokine that induces insulin resistance.
3441 17637478 Activation of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma) plays an important role in adipogenesis, insulin resistance, and glucose homeostasis.
3442 17639021 To assess effects on insulin action, we used retroviral delivery of short hairpin RNA to reduce Lcn2 levels in 3T3-L1 adipocytes.
3443 17639021 Expression of Lcn2 is elevated by agents that promote insulin resistance and is reduced by thiazolidinediones.
3444 17639021 Exogenous Lcn2 promotes insulin resistance in cultured hepatocytes.
3445 17639022 Glucagon-like peptide-1 (GLP-1) rescues insulin secretory deficiency in type 2 diabetes partly via cAMP actions on exchange protein directly activated by cAMP (Epac2) and protein kinase A (PKA)-activated Rab3A-interacting molecule 2 (Rim2).
3446 17639022 GLP-1 stimulation of Munc13-1(+/-) islets normalized the reduced biphasic insulin secretion by its actions on intact islet cAMP production and normal Epac2 and Rim2 levels.
3447 17646208 Tumor necrosis factor (TNF)-alpha is known to affect insulin sensitivity, glucose, and lipid metabolism through alternative and redundant mechanisms at both translational and post-translational levels.
3448 17724330 Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility.
3449 17764005 Insulin level and brain infarcts were associated with more severe WML and statin use with less severe WML (all p < 0.05).
3450 17785630 Resistin, a recently discovered proinflammatory cytokine, has been variably associated with insulin resistance, inflammation, and renal dysfunction.
3451 17785630 Higher plasma resistin levels were associated with a higher urine albumin:creatinine ratio in black subjects with diabetes (P<0.0001) and non-Hispanic white subjects with diabetes (P=0.032), independent of coronary heart disease risk factors, hypertension medication use, and statin use; the association remained significant after additional adjustment for homeostasis model assessment for insulin resistance and C-reactive protein.
3452 17805301 During feeding, increases in circulating pancreatic insulin inhibit hepatic glucose output through the activation of the Ser/Thr kinase AKT and subsequent phosphorylation of the forkhead transcription factor FOXO1 (refs 1-3).
3453 17805301 Here we show in mice that insulin inhibits gluconeogenic gene expression during re-feeding by promoting the phosphorylation and ubiquitin-dependent degradation of TORC2.
3454 17805301 Insulin disrupts TORC2 activity by induction of the Ser/Thr kinase SIK2, which we show here undergoes AKT2-mediated phosphorylation at Ser 358.
3455 17825789 Collectrin is involved in the process of vesicle transport and membrane fusion and thus it delivers insulin for exocytosis or various membrane proteins to apical plasmalemma and primary cilia.
3456 17846745 In multivariate models, controlling for known determinants of insulin sensitivity (i.e. sex, age, BMI and glucose tolerance) as well as factors potentially affecting glucagon and proinsulin (i.e. fasting plasma glucose and C-peptide concentrations), glucagon and proinsulin were still positively associated, and adiponectin was negatively associated, with IR.
3457 17875968 Exposure of cultured human umbilical vein endothelial cells to either peroxynitrite (ONOO-) or high glucose significantly inhibited both basal and insulin-stimulated Akt phosphorylation at Ser473 and Akt activity in parallel with increased apoptosis, phosphorylation, and activity of phosphatase and tensin homologue deleted on chromosome 10 (PTEN).
3458 17875968 Finally, treatment with Tempol, a superoxide dismutase mimetic, and insulin, both of which reduced the ONOO- formation, markedly reduced diabetes-enhanced LKB1-Ser428 phosphorylation, PTEN, and apoptosis in the endothelium of mouse aortas.
3459 17877544 Activities of the dominant incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, include glucose-dependent stimulation of insulin secretion and, in preclinical models, improvement in islet beta-cell mass.
3460 17881328 This modification increases self-association and enables albumin binding of insulin detemir.
3461 17883705 Lastly, five of 10 patients with T1D were studied for PMCA4b expression after insulin treatment, with four of five recovering normal expression (96% +/- 15%; n = 5).
3462 17884445 In both sexes, low SHBG was associated independently with high triglyceride/low high-density lipoprotein dyslipidemia and with MS, at significant 2.2- to 4.5-fold odds ratios, independent of waist circumference or homeostasis model assessment of insulin resistance index.
3463 17884445 In an elderly population with prevalent MS, low SHBG levels significantly associate with high triglyceride/low high-density lipoprotein dyslipidemia, MS, and, in women alone, diabetes and a dyslipidemia marking small dense low-density lipoprotein particles, all independent of abdominal obesity and insulin resistance.
3464 17885426 Fatty acids appeared to compromise insulin signaling by protein kinase C activation.
3465 17893258 In healthy subjects, acute hyperinsulinaemia is associated with an increase in plasma resistin independently of ARB, while plasma adiponectin is not influenced by insulin or ARB.
3466 17893258 The expressions of both resistin and adiponectin in s.c. adipose tissue are stimulated by acute hyperinsulinaemia, whereas losartan attenuates their insulin-stimulated expressions.
3467 17893259 These results suggest that ZFP36 gene expression in omental adipose tissue, but not in abdominal s.c. fat, may offer partial protection against the development of insulin resistance and diabetes.
3468 17893260 Previously, it has been demonstrated that receptor protein tyrosine phosphatase sigma (RPTPsigma) is involved in glucose homeostasis and insulin signaling in several animal models.
3469 17903324 Adipocytes also secrete adiponectin, enhancing insulin sensitivity and preventing atherosclerosis.
3470 17412344 Insulin stimulates Pit-1 mRNA modestly (*p<0.01 versus control), an effect inhibited by PD98059 but not by wortmannin.
3471 17412344 Pit-1 protein expression is induced by insulin, an effect also inhibited by PD98059 (*p<0.001 versus insulin alone).
3472 17184146 We conclude that administration of PPAR-alpha agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus.
3473 17575262 Animal models and patients with type 2 diabetes exhibit elevated levels of circulating retinol-binding protein (RBP4), and RBP4 can induce insulin resistance in mice.
3474 17575262 However, little is known about how RBP4 affects insulin signaling.
3475 17575262 RBP4-treated adipocytes exhibited the same molecular defects in insulin signaling, via IRS1 to MAP kinase, as in adipocytes from patients with type 2 diabetes.
3476 17575262 Without affecting autophosphorylation of the insulin receptor, RBP4 blocked the insulin-stimulated phosphorylation of IRS1 at serine (307) [corresponding to serine (302) in the murine sequence] and concomitantly increased the EC50 (from 0.5 to 2 nM) for insulin stimulation of IRS1 phosphorylation at tyrosine.
3477 17575262 The EC50 for insulin stimulation of downstream phosphorylation of MAP kinase ERK1/2 was increased (from 0.2 to 0.8 nM) by RBP4.
3478 17575262 However, the sensitivity to insulin for downstream signaling to control of protein kinase B and glucose uptake was not affected by RBP4.
3479 17575262 When insulin-resistant adipocytes from patients with type 2 diabetes were incubated with antibodies against RBP4, insulin-induced phosphorylation of IRS1 at serine (307) was normalized and the EC50 for insulin stimulation of ERK1/2 phosphorylation was reduced.
3480 17608757 Postoperative IL-18 concentrations in the multiple regression analysis were significantly associated with postoperative homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.092, P = 0.019) and triglycerides (beta = 0.40, P = 0.036).
3481 17636114 Single nucleotide polymorphisms (SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in the Finnish Diabetes Prevention Study (DPS).
3482 17652184 Adenovirus-mediated overexpression of miR-29a/b/c in 3T3-L1 adipocytes could largely repress insulin-stimulated glucose uptake, presumably through inhibiting Akt activation.
3483 17652184 In this paper, we demonstrate that Akt is not the direct target gene of miR-29 and that the negative effects of miR-29 on insulin signaling might be mediated by other unknown intermediates.
3484 17667847 While PGR did not alter insulin sensitivity in either strain, female DBA/2 mice had significantly decreased insulin levels during glucose tolerance testing.
3485 17761671 As a result, acutely diabetic NOD mice do not require insulin injections for survival for a significant time period, thus providing a promising clue to effect IDDM reversal in humans.
3486 17785466 After observing that expression of two NR4A orphan nuclear receptors, NR4A3 and NR4A1, was altered by insulin in cDNA microarray analyses of human skeletal muscle, we studied whether these receptors could modulate insulin sensitivity.
3487 17785466 We found that both NR4A3 and NR4A1 were induced by insulin and by thiazolidinedione drugs (pioglitazone and troglitazone) in 3T3-L1 adipocytes.
3488 17785466 Furthermore, gene expression of NR4A3 and NR4A1 was reduced in skeletal muscles and adipose tissues from multiple rodent models of insulin resistance.
3489 17785466 To determine whether NR4A3 could modulate insulin sensitivity, 3T3-L1 adipocytes were stably transduced with NR4A3 or LacZ (control) lentiviral vectors.
3490 17785466 Thus, NR4A3 and NR4A1 are attractive novel therapeutic targets for potential amelioration of insulin resistance, and treatment and prevention of type 2 diabetes and the metabolic syndrome.
3491 17869225 In this study, we have demonstrated that anthocyanin (cyanidin 3-glucoside; C3G) which is a pigment widespread in the plant kingdom, ameliorates hyperglycemia and insulin sensitivity due to the reduction of retinol binding protein 4 (RBP4) expression in type 2 diabetic mice.
3492 17920636 These cell lines have been developed by stably and constitutively expressing human proinsulin with a furin-cleavable site, whereas expression of furin is regulated by glucose concentration.
3493 17922004 We also show that oleic acid treatment decreases the insulin sensitivity of heart muscle cells, and this sensitivity is completely restored by transfection with SNAP23.
3494 17922004 Thus, SNAP23 might be a link between insulin sensitivity and the inflow of fatty acids to the cell.
3495 17937928 We therefore conclude that genetic inactivation of GIP signaling can prevent the development of aging-associated insulin resistance through body composition changes.
3496 17939176 We conclude that reduced TG2 activity can contribute to disorders of glucose metabolism possibly via an impairment of insulin secretion.
3497 17940018 Here, we show that LCAD knockout mice develop hepatic steatosis, which is associated with hepatic insulin resistance, as reflected by reduced insulin suppression of hepatic glucose production during a hyperinsulinemic-euglycemic clamp.
3498 17950098 Adiponectin may play an important role in the regulation of body weight, insulin resistance, and cardiovascular disease.
3499 17950099 Serum HMW adiponectin level was inversely correlated with homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.375, P < .0001) even after adjustment for age and body mass index (r' = -0.245, P < .0001).
3500 17951542 Bioinformatics studies showed that RESP18 shares sequence homology with the luminal region of IA-2, a dense core vesicle (DCV) transmembrane protein involved in insulin secretion.
3501 17952831 In rodents, resistin is produced by adipose tissue, and is a significant regulator of glucose metabolism and insulin sensitivity.
3502 17952832 Tissue-specific genetic knockout of GLUT4 expression in adipose tissue or muscle of mice has provided new insights into the pathogenesis of insulin resistance.
3503 17952832 Therefore, RBP4 appears to play an important role in mediating adipose tissue communication with other insulin target tissues in insulin resistant states.
3504 17952836 Insulin resistance and vascular function are directly affected these factors, i.e., by free fatty acids, inflammatory adipocytokines, thrombotic and antifibrinolytic factors and by adiponectin, and adipokine with insulin sensitizing and anti-inflammatory actions.
3505 17952839 This reduction was associated with enhanced tyrosine phosphorylation of IRS2 and serine (473) phosphporylation of Akt, indicating improved hepatic insulin signaling.
3506 17956306 We were also able to demonstrate the direct effect of insulin and the counter-regulatory hormones on the regulation of cystathionine beta-synthase and BHMT, which accounts for the changes in the activities of these two enzymes seen in diabetes mellitus.
3507 17956334 IL-6 treatment of myotubes increases fatty acid oxidation, basal and insulin-stimulated glucose uptake and translocation of GLUT4 to the plasma membrane.
3508 17966038 HLA-DQ8 transgenic mice expressing the costimulatory molecule, B7.1 (RIP.B7.1), or the proinflammatory cytokine, TNF-alpha (RIP.TNF) or both (RIP.B7.RIP.TNF) under the control of rat insulin promoter (RIP) were used.
3509 17966842 After 5-week insulin therapy, there was a significant decrease in the expression of CCR5 on the surface of these cells and a significant fall in serum levels of RANTES, IL-6, TNF-alpha and hsCRP.
3510 17973869 The G allele carriers who have reduced plasma concentrations of adiponectin may have associated insulin resistance.
3511 17409029 Increased glucose AUC and reduced early insulin release but not glucose tolerance categories were associated with a reduced pulmonary function (FEV(1)).
3512 17127041 In VSMCs from non-diabetic rats, insulin was able to reduce (10 nM) or suppress (100 nM) the protein overexpression of CD36 induced by AGEs-BSA.
3513 17553627 Brain-derived neurotrophic factor (BDNF) modulates the secretion and actions of insulin, leptin, ghrelin, various neurotransmitters and peptides, and pro-inflammatory cytokines involved in energy homeostasis suggesting that it (BDNF) has a significant role in the pathobiology of obesity and type 2 diabetes mellitus.
3514 17178123 Adiponectin and resistin are proteins that affect insulin resistance and atherosclerosis significantly.
3515 17761380 HMW adiponectin has been suggested to be a better predictor of metabolic variables, and it was recently reported that the ratio of HMW to total adiponectin or to LMW, not the absolute amount of plasma adiponectin, might be crucial in determining insulin sensitivity.
3516 17891462 During this period, beta cells also declined sharply whereas glucagon and somatostatin cells increased, with occasional islet cells co-expressing insulin and glucagon.
3517 17936398 Resistin was initially identified as a protein, secreted by adipocytes, which inhibits insulin action and adipose differentiation.
3518 17936398 These results suggest RELMbeta expression to be regulated directly by nutrients such as glucose and saturated free fatty acids including stearic acid, as well as by hormones including insulin and TNFalpha.
3519 17940115 At age 15 yr, leptin therapy was initiated, and after 1 yr, his insulin requirements fell to 1 U/kg.d, his glycemic control improved (HbA 1c 8.4%), and both his triglycerides and transaminases normalized.
3520 17940115 At age 13 yr, leptin therapy was started, and after 1 yr, her glycemic control improved (HbA 1c 7.3%) and her insulin requirements decreased (17 U/kg.d).
3521 17956948 We therefore hypothesized that type 2 diabetic patients using exceptionally high doses of insulin might respond well to addition of a PPARgamma agonist.
3522 17956948 We determined the effect of the PPARgamma agonist rosiglitazone on liver fat and directly measured hepatic insulin sensitivity in 14 patients with type 2 diabetes (aged 51 +/- 3 yr, body mass index 36.7 +/- 1.1 kg/m2), who were poorly controlled (glycosylated hemoglobin A 1c (HbA 1c) 8.9 +/- 0.4%) despite using high doses of insulin (218 +/- 22 IU/d) in combination with metformin.
3523 17971513 Gastric inhibitory polypeptide (GIP) is an incretin that potentiates insulin secretion from pancreatic beta-cells by binding to GIP receptor (GIPR) and subsequently increasing the level of intracellular adenosine 3',5'-cyclic monophosphate (cAMP).
3524 17971513 In high-fat diet-fed obese mice (HFD mice), blood glucose levels were maintained by compensatory increased insulin secretion (n = 8, P < 0.05), and cAMP production (n = 6, P < 0.01) and insulin secretion (n = 10, P < 0.05) induced by GIP were significantly increased in isolated islets, suggesting hypersensitivity of the GIPR.
3525 17971514 The insulin-induced glucose uptake was enhanced by berberine in the absence of change in IRS-1 (Ser307/312), Akt, p70 S6, and ERK phosphorylation.
3526 17991720 Both peroxisome proliferator-activated receptor-alpha (PPARalpha) and pancreatic/duodenal homeobox-1 (PDX-1) have been reported to be associated with glucose-stimulated insulin secretion (GSIS), but the relationship between PPARalpha and PDX-1 is not yet fully understood.
3527 17991720 In turn, this enhanced expression led to an increase in PDX-1 mRNA and nuclear protein, as well as DNA binding activity of PDX-1 with the insulin promoter.
3528 18003719 To examine whether p38 MAPK affects insulin's cardioprotection against ischemia-reperfusion injury, we studied overnight-fasted adult male rats by use of an in vivo rat model of myocardial ischemia-reperfusion.
3529 18003719 Treatment of animals with SB-239063, a potent and specific inhibitor of p38 MAPK, 10 min before reperfusion enabled insulin-mediated myocardial protection in InsulinAR rats.
3530 18003719 We conclude that insulin protects myocardium against ischemia-reperfusion injury when given prior to ischemia or reperfusion, and activation of p38 MAPK abolishes insulin's cardioprotective effect.
3531 18005249 In mammals, the Sir2 ortholog Sirt1 promotes fat mobilization, fatty acid oxidation, glucose production, and insulin secretion in response to nutrient availability.
3532 18037364 At 36 weeks of age, the rats were killed, and we evaluated bone formation and the effect of insulin on bone formation, blood and urine analyses, bone mineral density (BMD), histomorphometry, and mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN).
3533 18078308 The in vitro insulinotropic effects of DB-GLP-1 and DBP-GLP-1 showed potent biological activity in a dose-dependent manner, which resembled that of native GLP-1 in terms of stimulating insulin secretion in isolated rat islets of Langerhans.
3534 18078928 Tumor necrosis factor (TNF)-alpha and local activation of the renin-angiotensin system may contribute to insulin resistance and atherosclerosis.
3535 18082135 In vitro studies have implicated the c-Jun amino terminal kinase (JNK) in cytokine-induced pancreatic injury leading to a loss of insulin production and hyperglycemia.
3536 18171427 While it remains to be established whether the increased expression of SOCS is a cause or a consequence of insulin resistance, a large body of observations supports a role for SOCS proteins in the disease process found in states with insulin resistance.
3537 18171435 Evidence now suggests that the improvements in insulin sensitivity associated with exercise training are also related to changes in the expression and/or activity of proteins involved in insulin signal transduction in skeletal muscle such as the AMP-activated protein kinase (AMPK) and the protein kinase B (Akt) substrate AS160.
3538 18178160 Insulin treatment also led to the up-regulation of human sodium/glucose transporter 1 (hSGLT1), which further increases intracellular glucose levels.
3539 18178618 On granule exocytosis, the ICA512 cytoplasmic domain is cleaved and the resulting cytosolic fragment (ICA512-CCF) moves into the nucleus where it enhances the levels of phosphorylated STAT5 and STAT3, thereby inducing insulin gene transcription and granule biogenesis.
3540 18178618 Up-regulation of cyclin D1 and D2 by ICA512-CCF is affected by knockdown of STAT3 and STAT5, respectively, whereas it does not require insulin signaling.
3541 18180399 In vitro gene expression analysis in human coronary endothelial cells revealed that resistin induced fatty acid binding protein, a key molecule of insulin resistance, diabetes, and atherosclerosis.
3542 17215165 Our findings suggest that plasma leptin concentration is independently associated with the development of insulin resistance in a non-selected prepubertal population.
3543 17895880 The release of adiponectin was enhanced by insulin and by inhibition of endogenous tumor necrosis factor (TNFalpha) using etancercept.
3544 18177263 Over-expression of miR124a leads to exaggerated hormone release under basal conditions and a reduction in glucose-induced secretion. miR96 increases mRNA and protein levels of granuphilin, a negative modulator of insulin exocytosis, and decreases the expression of Noc2, resulting in lower capacity of MIN6B1 cells to respond to secretagogues.
3545 18191647 The current wisdom indicates that insulin's positive effects, normoglycemia, vasodilation, and anti-inflammation, are mediated by the canonical phosphoinositide 3-kinase (PI3K)/Akt pathway whereas the negative effects are mediated by the mitogen-activated protein kinase (MAPK)/extracellular regulated kinase (ERK) pathway.
3546 18218037 Our results show that IL-10 gene polymorphism of PCOS patients has no effect on inflammatory markers, metabolic parameters (fasting insulin, fasting glucose, HOMA-IR), carotid intimae media thickness and Ferriman- Gallwey scoring.
3547 18221786 We describe the development and optimisation of an immunocapture-based assay that uses the fluorogenic peptide substrate (Mca-RPPGFSAFK(Dnp)) and allows the specific measurement of insulin-degrading enzyme (IDE) activity in brain tissue homogenates.
3548 18241357 Akt/PKB is associated with a downstream insulin signaling, and PKCbeta attenuates insulin-stimulated Akt phosphorylation.
3549 18241861 Transgenic mice that overexpress GDNF in glia exhibit increased beta-cell mass, proliferation, and insulin content.
3550 18295300 Wrn null mice had significantly increased body weights, increased serum insulin levels, impaired glucose tolerance, and insulin resistance during 4 months of eating the diabetogenic diet.
3551 18296638 Insulin resistance, a hallmark of type 2 diabetes and obesity, is associated with increased activity of MAP and stress-activated protein (SAP) kinases, which results in decreased insulin signaling.
3552 18296638 MKP-4 also reversed the effect of TNF-alpha to inhibit insulin signaling; alter IL-6, Glut1 and Glut4 expression; and inhibit insulin-stimulated glucose uptake in 3T3-L1 adipocytes.
3553 18296638 Thus, MKP-4 has a protective effect against the development of insulin resistance through its ability to dephosphorylate and inactivate crucial mediators of stress-induced insulin resistance, such as ERK and JNK, and increasing MKP-4 activity might provide a therapy for insulin-resistant disorders.
3554 18310453 The dual control of insulin secretion via the K(ATP) channel-dependent triggering pathway and K(ATP) channel-independent amplifying pathway was unaltered in IA-2/IA-2beta KO islets, and so were the potentiations by acetylcholine or cAMP (forskolin).
3555 18324929 High levels of circulating retinol-binding protein 4 (RBP4) and baseline expression of adipogenic genes correlate with subsequent improvement in insulin sensitivity following Thiazolidinedione (TZD) treatment.
3556 18328348 The objective of the study was to investigate the effects of rosiglitazone (RSG), a thiazolidinedione derivative, on body fat distribution and insulin sensitivity in Korean subjects with type 2 diabetes mellitus.
3557 18330534 The thiazolidinediones (glitazones) significantly improve insulin sensitivity, diminish fat accumulation in the liver and increase circulating levels of adiponectin.
3558 18333795 Isolated islets were placed in collagen gels, and they exhibited fourfold more insulin release than islets not in collagen.
3559 18333795 The insulin released by beta-cells in islets encapsulated in collagen exhibited unobstructed diffusion within the collagen gels.
3560 18333892 However, hyperglycaemia and glycated haemoglobin were worsened, glucose tolerance further decreased and insulin sensitivity was impaired by (Pro3)GIP.
3561 18333892 These data indicate that the beneficial actions of the GIP-R antagonist, (Pro3)GIP, in obesity-diabetes appear to be largely mediated through insulin-dependent mechanisms that merit further investigation.
3562 17645557 Decreased levels of adiponectin are linked with visceral obesity, insulin resistance states, and cardiovascular diseases.
3563 17686902 Thiazolidinediones (TZD) are insulin sensitizing agents currently used for the treatment of type 2 diabetes and are widely used as adipogenic agents because they are ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), a key adipogenic transcription factor.
3564 17940160 Furthermore, down-regulation of PTP1B activity is possible by the use of pharmacological agonists of nuclear receptors that restore insulin sensitivity in the presence of TNF-alpha.
3565 17949947 The resulting HLA-DR4/GAD-TcR transgenic mice on a Rag2(o/o)/I-Ab(o/o)/B6 background exhibited a CD4(+) infiltrate into pancreatic islets that correlated with a loss of insulin in infiltrated islets.
3566 18088079 The aim of this study was to elucidate the effect of C-peptide and insulin as a reference on the eNOS expression in the early phase of type 1 diabetic rat kidney.
3567 18187553 Exogenous TNF-alpha infusion increased c-Jun N-terminal kinase phosphorylation and insulin receptor substrate-1 serine 307 phosphorylation, and inhibited insulin-induced signaling in liver.
3568 18202124 Insulin-stimulated IRS tyrosine phosphorylation was impaired by overepxression of PKC-zeta for IRS-1, -3, and -4 but not IRS-2.
3569 18202124 Significant insulin-stimulated increases in PI3K activity was coimmunoprecipitated with all IRS isoforms.
3570 18202124 In cells overexpressing PKC-zeta there was marked inhibition of insulin-stimulated PI3K activity associated with IRS-1, -3 and -4 but not IRS-2.
3571 18202124 That is, PI3K activity associated with IRS-2 in response to insulin was similar in control cells and cells overexpressing PKC-zeta.
3572 18202124 We conclude that IRS-3 and -4 are novel substrates for PKC-zeta that may participate in a negative feedback pathway for insulin signaling similar to IRS-1.
3573 18202127 Interestingly, inhibiting Raf-1 kinase blocked proliferation stimulated by low, but not high (superphysiological), insulin doses.
3574 18202127 Overexpression of Raf-1 was sufficient to increase proliferation in the absence of insulin, whereas a dominant-negative Raf-1 reduced proliferation in the presence of 200-pm insulin.
3575 18218179 In two previously reported multi-center, randomized, open-label, comparator (insulin) controlled trials in patients with type 2 diabetes sub-optimally controlled with metformin and a sulfonylurea, treatment with exenatide and insulin analogue therapy produced similar reductions in glycosylated hemoglobin A(1c) (A1C).
3576 18234957 All three members of the PPAR nuclear receptor subfamily, PPARalpha, -beta/delta, and -gamma, are critical in regulating insulin sensitivity, adipogenesis, lipid metabolism, inflammation, and blood pressure.
3577 18235054 Both biomarkers of endothelial dysfunction correlated significantly with markers of inflammation (interleukin-6 [IL-6] and C-reactive protein [CRP]), hepatic function (gamma-glutamyl transferase [GGT]), and insulin resistance, with t-PA showing stronger associations with adiposity, hepatic function, and insulin resistance than vWF. t-PA was also significantly and inversely associated with adiponectin.
3578 18235054 Subsequent adjustment for insulin attenuated the association further, but t-PA was still associated with a significant increase in risk (1.66 [0.96-2.85]; P(trend) = 0.02). t-PA antigen, but not vWF antigen, is independently associated with risk of type 2 diabetes.
3579 18249022 The functional variant Trp64Arg in the beta(3)-adrenergic receptor has previously been examined for association with obesity and insulin resistance with ambiguous results.
3580 18252893 Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple beneficial effects on glucose homeostasis and insulin sensitivity in animal models.
3581 18252893 Serum FGF21 correlated positively with adiposity, fasting insulin, and triglycerides but negatively with HDL cholesterol, after adjusting for age and BMI.
3582 18268048 The aim of our study was to examine the role of the signal transducers and activators of transcription 3 (STAT3) in insulin signaling.
3583 18268048 During feeding, both mRNA and protein levels of GSK-3beta decreased in Stat3(f/+) mice, which reflected the need of hepatocytes for insulin to induce glycogen synthesis.
3584 18268048 These data indicate that STAT3 sensitizes insulin signaling by negatively regulating GSK-3beta.
3585 18268048 Inactivation of STAT3 in the liver contributes significantly to the pathogenesis of insulin resistance.
3586 18270300 Insulin increases CCL2 expression in adipose tissue and in serum more in insulin-resistant obese than in insulin-sensitive lean mice, but whether this is true in humans is unknown.
3587 18270300 We compared basal expression and insulin regulation of CCL2 and CCL3 in adipose tissue and MCP-1 and MIP-1alpha in serum between insulin-resistant and insulin-sensitive human subjects.
3588 18270300 Insulin increased MCP-1 gene and protein expression significantly more in the insulin-resistant than in the insulin-sensitive subjects.
3589 18270300 Insulin regulation of CCL2 differs between insulin-sensitive and -resistant subjects in a direction that could exacerbate adipose tissue inflammation.
3590 18270301 Although IGF-I might not promote islet cell growth, its overexpression is clearly antidiabetic by improving islet cell survival and/or providing insulin-like effects.
3591 18276765 Recently, Rab GTPase-activating protein AS160, a substrate of Akt, was shown to be involved in insulin modulation of GLUT4 trafficking in skeletal muscle and adipose tissue.
3592 18276765 For knockdown experiments, transformed mouse insulin-secreting MIN6B1 cells were transfected with pSUPER-GFP plasmid encoding a small hairpin RNA against insulin receptor substrate (IRS)-2, AS160, or a negative control.
3593 18276765 This study shows for the first time that AS160, previously recognized as a key player in insulin signaling in skeletal muscle and adipose tissue, is also a major effector of protein kinase B/Akt signaling in the beta-cell.
3594 18278435 Our results suggest that the imidazoline RX871024 causes death of highly proliferating insulin-secreting cells, putatively via augmentation of JNK activity, a finding that may impact on the possibility of using compounds of similar activity in the treatment of diabetes.
3595 18285549 We hypothesized that circulating levels of surfactant protein (SP)-A, which reflects interstitial lung injury, could be associated with altered glucose tolerance and insulin resistance.
3596 18285549 Insulin sensitivity (P = 0.003) contributed independently to 22% of SP-A variance among all subjects.
3597 18285549 In subjects with altered glucose tolerance, insulin sensitivity (P = 0.01) and fasting triglycerides (P = 0.02) contributed to 37% of SP-A variance.
3598 18285549 Lung-derived SP-A protein was associated with altered glucose tolerance and insulin resistance in 164 nonsmoking men.
3599 18285554 The primary comparisons were insulin sensitivity by hyperinsulinemic-euglycemic clamp and skeletal muscle mitochondrial capacity for oxidative phosphorylation (OXPHOS) by measuring mitochondrial DNA copy number (mtDNA), OXPHOS gene transcripts, citrate synthase activity, and maximal mitochondrial ATP production rate (MAPR).
3600 18285556 Berberine (BBR) activates AMP-activated protein kinase (AMPK) and improves insulin sensitivity in rodent models of insulin resistance.
3601 18285556 Complex I of the respiratory chain represents a major target for compounds that improve whole-body insulin sensitivity through increased AMPK activity.
3602 18299442 Receiver operating characteristics analysis was used to determine diagnostic thresholds for insulin receptoropathy in severe insulin resistance for adiponectin and for the insulin-regulated hepatic proteins sex hormone-binding globulin (SHBG) and IGF binding protein-1 (IGFBP-1).
3603 18316359 Our aim was to evaluate the relationship between insulin resistance and the expression and regulation of forkhead box-containing protein O subfamily-1 (FOXO1), a transcription factor that mediates the effect of insulin on the gluconeogenic genes PEPCK and glucose-6-phosphatase catalytic subunit (G6PC).
3604 18316359 RESULTS; Expression of PEPCK was higher in steatohepatitis compared with steatosis alone and normal liver, and it was correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) index.
3605 18316359 FOXO1 expression and activity are increased in patients with steatohepatitis, and mRNA levels are correlated with hepatic insulin resistance.
3606 18334611 In normal, healthy human subjects insulin increased the mRNAs of a number of inflammatory genes (CCL2, CXCL2 and THBD) and transcription factors (ATF3, BHLHB2, HES1, KLF10, JUNB, FOS, and FOSB).
3607 18334611 The results of the present study demonstrate that insulin acutely regulates the levels of mRNAs involved in inflammation and transcription and identifies several candidate genes, including HES1 and BHLHB2, for further investigation.
3608 18349107 Little is known about the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms and the presence of insulin resistance and the early evolution of atherosclerosis in nondiabetic subjects with cardiovascular disease (CAD) and stent implantation.
3609 18356850 The variations in perilipin gene (PLIN) were previously associated with obesity and insulin sensitivity.
3610 18366646 Common ARNT variants are unlikely to explain the linkage signal on chromosome 1q, but may alter insulin secretion in nondiabetic subjects.
3611 18389389 Although adiponectin levels are associated with obesity and insulin insensitivity, the role of adiponectin in the progression to diabetes in non-obese subjects is unclear.
3612 18408913 We postulated that the mechanism of age-dependent type 2 diabetes in this model relates to caveolin-1 status in skeletal muscle, which appears to regulate insulin sensitivity in the mice.
3613 18408913 In 30-week-old C57BL/6 and JYD mice, the basal levels of IRS-1, Akt and peroxisome proliferator-activated receptor-gamma decreased, as did insulin-stimulated phosphorylation of Akt and insulin receptor beta.
3614 18413218 Elevated CRP in Type 1 diabetes was associated with poor glycemic control, larger body habitus, and other factors that comprise the insulin resistance syndrome.
3615 18413223 Leptin has been shown to be able to modulate insulin secretion.
3616 18413223 The objective of this study was to investigate the influence of Lys656Asn polymorphism in the LEPR gene on serum insulin, glucose values, and insulin resistance in the fasted state among obese men and women without diabetes mellitus.
3617 18419637 However, the fatty liver could contribute in the same way as visceral adipose tissue to insulin resistance, systemic inflammation and oxidative stress, while the decreased serum adiponectin concentrations might also be part of the mechanism.
3618 18430365 RhGLP-1 (7-36) stimulates the secretion and expression of amylin, and exerts a beneficial effect on the ratio of amylin to insulin mRNA.
3619 18430992 Reduction in central insulin decreases neuronal nitric oxide synthase and increases inducible synthase activity.
3620 18434357 However, there was no insulin-stimulated protein kinase B (PKB) Ser473 or glycogen synthase kinase (GSK)-3beta Ser9 phosphorylation in the LIP rats, compared with at least a twofold increase over basal in GLYC rats for both proteins. c-Jun N-terminal kinase, inhibitor of kappa kinase beta and inhibitor of nuclear factor-kappaB phosphorylation and total protein expression, as well as Ser307-IRS-1 phosphorylation, were not altered by lipid infusion compared with GLYC infusion.
3621 18434357 These data indicate that acute, physiological elevation in FFA has a greater impact on insulin signalling downstream of IR and IRS-1, at the level of PKB and GSK-3beta, and that under these conditions stress signalling pathways are not significantly stimulated.
3622 18434357 Decreased PKB and GSK-3beta phosphorylation in RQ may therefore be primary determinants of the reduced insulin action observed in situations of acute FFA oversupply.
3623 18437350 This study investigates whether the glycation inhibitors aminoguanidine and pyridoxamine, the insulin sensitiser metformin and the cross-link breaker alagebrium can inhibit and/or reverse the methylglyoxal-mediated glycation of ApoA-I and whether these changes can preserve or restore the ability of ApoA-I to activate LCAT.
3624 17938503 In mature beta-cells, PDX-1 transactivates the insulin and other genes involved in glucose sensing and metabolism such as GLUT2 and glucokinase.
3625 17938503 MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription.
3626 18207474 DAG is identified as a potential mediator of lipid-induced insulin resistance, as increased DAG levels are associated with protein kinase C activation and a reduction in both insulin-stimulated IRS-1 tyrosine phosphorylation and PI3 kinase activity.
3627 18281274 PTP1B overexpression in high fat-fed mice coincided with increased adipose tissue expression of the macrophage marker CD68 and TNFalpha, which is implicated in causing obesity-induced insulin resistance.
3628 18285412 Our objective was to investigate the impact of rs7754840 of CDKAL1 on insulin secretion, insulin sensitivity, and risk of type 2 diabetes.
3629 18285412 In study 2, rs7754840 was significantly associated with type 2 diabetes (P = 0.022) and markers of impaired insulin release [insulinogenic index (IGI), P = 0.012] in 2405 men with normal glucose tolerance. rs7754840 of CDKAL1 was associated with markers of impaired insulin secretion in two independent studies.
3630 18285412 Therefore, CDKAL1 is likely to increase the risk of type 2 diabetes by impairing insulin secretion.
3631 18309377 Inhibiting the insulin receptor with neutralizing antibodies or antisense oligonucleotides had no effect on EPC outgrowth.(1) In contrast, targeting the human insulin-like growth factor 1 (IGF-1) receptor with neutralizing antibodies significantly suppressed insulin-induced outgrowth of EPCs from both healthy controls and patients with type 2 diabetes.
3632 18309377 This IGF-1 receptor-mediated insulin effect on EPC growth was at least in part dependent on MAP kinases(2) and was abrogated when extracellular signal-regulated kinase 1/2 (Erk1/2) and protein kinase 38 (p38) activity was inhibited.
3633 18349383 In the absence of alterations in plasma adiponectin concentrations, acceleration of insulin-stimulated glucose turnover in skeletal muscle of mUCP1 TG mice was accompanied by increased phosphorylated Akt-to-Akt and phosphorylated AMP-activated protein kinase (AMPK)-to-AMPK ratios compared with WT mice.
3634 18349383 UCP1-mediated uncoupling of oxidative phosphorylation in skeletal muscle was paralleled by AMPK activation and thereby stimulated insulin-mediated glucose uptake in skeletal muscle.
3635 18375050 In the pancreas, SST is a potent regulator of insulin and glucagon secretion.
3636 18381287 To investigate the effects of ACC1 inhibition on insulin secretion, three small interfering RNA (siRNA) duplexes targeting ACC1 (siACC1) were transfected into the INS-1-derived cell line, 832/13; the most efficacious duplex was also cloned into an adenovirus and used to transduce isolated rat islets.
3637 18385532 DHMEQ suppressed TNF-alpha-induced NF-kappaB activation and partially ameliorated glucose-stimulated insulin secretion in a dose-dependent manner.
3638 18385532 DHMEQ also partially ameliorated decreased cell viability and insulin mRNA level induced by TNF-alpha.
3639 18388859 ProF binds to the transcription factor Foxo1 (Forkhead box O1), a negative regulator of insulin action and adipogenesis, and facilitates the phosphorylation and thus inactivation of Foxo1 by Akt.
3640 18400427 Insulin mimetic action of Fructus Corni on dexamethasone and 8-bromo-cAMP induced phosphoenolpyruvate carboxykinase (PEPCK) expression in H4IIE cells was investigated.
3641 18400427 Firstly, both methanol extract (CO-W-M) and fraction (CO-W-M2) had potent insulin mimic activity on PEPCK expression.
3642 18433874 Here, we review the physiological role of ghrelin in the regulation of insulin release and glucose metabolism, and a potential therapeutic avenue to treat type 2 diabetes by manipulating ghrelin and/or its signaling.
3643 18433874 Ghrelin inhibits insulin release in mice, rats and humans.
3644 18468239 These data indicate that cell-surface heparan sulfate proteoglycans are required for PDX-1 internalization and that PDX-1 protein transduction could be a valuable strategy for inducing insulin expression in pancreatic stem/progenitor cells without requiring gene transfer technology.
3645 18469441 This study investigated the effects of chronic hyperglycemia (glucotoxicity) on the expression of AT1Rs, and possibly thereby on oxidative stress-induced insulin release, in an INS-1E beta-cell line.
3646 18469441 Glucose-stimulated insulin secretion via AT1R activation was impaired by hyperglycemia.
3647 18469441 These data indicate that hyperglycemia-induced AT1R activation impairs insulin secretion; this impairment may be mediated via AT1R-dependent oxidative stress.
3648 18469500 Atorvastatin significantly decreased insulin-stimulated 2-deoxyglucose uptake in 3T3L1 adipocytes associated with the prevention of translocation of GLUT4 into the plasma membrane.
3649 18473773 Vasoconstriction is not its only effect; U-II and its receptor have been demonstrated in the central nervous system, where U-II induces a cardiovascular, behavioural, motor and endocrine response and in the kidney, where it seems to influence renal hemodynamics but also salt and water excretion, in rat pancreas where it inhibits insulin secretion, in the heart where it seems to play a role in cardiac hypertrophy and fibrosis.
3650 18478125 The incretin hormone GLP-1, which is used in clinical practice suppressed iNOS and ncNOS expression and activity with almost full restoration of insulin release and partial restoration of glucagon release.
3651 18481957 However, the cellular mechanisms by which changes in TCF7L2 levels may affect insulin secretion are unclear.
3652 18483661 Current strategies to treat type 2 diabetes (DMT2) include reducing insulin resistance using glitazones, supplementing with exogenous insulin, increasing endogenous insulin production with sulfonylureas and meglitinides, reducing hepatic glucose production through biguanides, and limiting postprandial glucose absorption with alpha-glucosidase inhibitors.
3653 18484561 To investigate blood apelin concentrations in patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM) who had no additional disorder and to investigate the association of apelin with adiponectin, body mass indexes (BMI) and insulin sensitivity.
3654 18485147 Moreover, a daily administration of nonglucidic nutrient EMS and metformin significantly decreased the levels of glucose, glycated hemoglobin, hydroxyproline, collagen content, extent glycation, fluorescence, neutral salt, acid and pepsin soluble collagen content, whereas it increased insulin, hemoglobin levels in diabetic rats.
3655 18081734 Resistin, secreted from adipocytes, causes insulin resistance in rodents.
3656 18225986 Similarly, after 16-day treatment with CBX, exogenous insulin evoked a significantly greater reduction in glucose concentrations (1.4- to 1.8-fold). 11beta-HSD1 gene expression was significantly down-regulated in liver, whereas glucocorticoid receptor gene expression was increased in both liver and adipose tissue following CBX treatment.
3657 17645558 Key secondary endpoints included the proportion of patients achieving recommended HbA(1c) and fasting plasma glucose (FPG) targets; change from baseline in FPG, insulin, C-reactive protein (CRP), adiponectin, free fatty acids and lipids; and percentage change in homeostasis model assessment-estimated insulin sensitivity and beta-cell function.
3658 18458149 Uncoupling protein-2 (UCP-2) also plays a crucial role in the palmitate inhibition of insulin secretion, as confirmed by knockdown experiments, but SREBP-1c contribution to UCP-2 regulation was partial.
3659 18496818 We found that the high glucose condition causes significant increasing Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1), leading to reduce insulin-stimulated phosphorylation of Akt.
3660 18496818 However, the treatment of EGCG improves insulin-stimulated downsignaling by reducing IRS-1 Ser307 phosphorylation.
3661 18496818 Together, our data suggest a putative link between high glucose and insulin resistance in HepG2 cells, and the EGCG treatment attenuates insulin signaling blockade by reducing IRS-1 Ser307 phosphorylation through the AMPK activation pathway.
3662 18519800 Plasma insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucose levels in response to acute oral fat diet were determined in Gpr40 mutant and control mice.
3663 18519800 Together, our data provide evidence that Gpr40 modulates FFA-stimulated insulin secretion from beta-cells not only directly but also indirectly via regulation of incretin secretion.
3664 18535190 After adjusting for age and sex, both IGF-1 and IL-6 were correlated with insulin resistance and individual components of MetS, but in opposite directions.
3665 18544643 Activation of either the AMPK or calcineurin pathway can also enhance the glycogen storage capacity and insulin sensitivity in skeletal muscle.
3666 18544705 Liver-specific inactivation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) by a dominant-negative transgene (l-SACC1 mice) impaired insulin clearance, caused insulin resistance, and increased hepatic lipogenesis.
3667 18544708 Selective sympathetic denervation of the liver completely blocked the effect of intracerebroventricular NPY administration on insulin action to suppress EGP (NPY/hepatic sympathectomy, 57 +/- 7%), whereas selective parasympathetic denervation had no effect (NPY/hepatic parasympathectomy, 29 +/- 7%).
3668 18551686 JNK phosphorylation was reduced by 126.7% with treatment of 1,25-dihydroxyvitamin D (p < 0.001). 1,25-Dihydroxyvitamin D had no effect on FFA-induced ERK phosphorylation (p = 0.84). 1,25-Dihydroxyvitamin D improved the FFA-induced insulin resistance in muscle cells.
3669 18556339 Insulin infusion significantly suppressed TLR1, -2, -4, -7, and -9 mRNA expression in MNCs within 2 h of the infusion, with a maximum fall at 4 h by 24 +/- 9%, 21 +/- 5%, 30 +/- 8%, 28 +/- 5%, and 27 +/- 10% (P < 0.05, for all), respectively, below the baseline.
3670 18559658 The remarkable increase in insulin secretory responses to intravenous glucose and Intralipid seen in WT mice after HFD was of much lower magnitude in GPR40 KO mice.
3671 18567819 As JNK can inhibit insulin action and activate proinflammatory pathways, ER stress activation of JNK may be a link between obesity, insulin resistance, and inflammation.
3672 18567820 No association with traits of insulin release or insulin action was observed for the THADA, ADAMTS9, or NOTCH2 variants.
3673 18567820 If replicated, our data suggest that type 2 diabetes at-risk alleles in the JAZF1, CDC123/CAMK1D, and TSPAN8 loci associate with various OGTT-based surrogate measures of insulin release, emphasizing the contribution of abnormal pancreatic beta-cell function in the pathogenesis of type 2 diabetes.
3674 18567823 Impaired insulin sensitivity is accompanied by increased activation of hepatic c-Jun NH(2)-terminal kinase/stress-activated protein kinase in Cd39/Entpd1 mice after injection of ATP in vivo.
3675 18577692 Insulin decreases adiponectin levels in humans.
3676 18577692 To determine the selective effects of insulin, glucose, or their combination on plasma adiponectin, clamps were performed in six healthy males on four occasions in a crossover design: 1) lower insulinemic-euglycemic clamp (100 pmol/l insulin, 5 mmol/l glucose) (reference clamp); 2) hyperinsulinemic-euglycemic clamp (400 pmol/l insulin, 5 mmol/l glucose); 3) lower insulinemic-hyperglycemic clamp (100 pmol/l insulin, 12 mmol/l glucose); and 4) hyperinsulinemic-hyperglycemic clamp (400 pmol/l insulin, 12 mmol/l glucose).
3677 18577692 We conclude that insulin suppresses plasma adiponectin levels already at a plasma insulin concentration of 100 pmol/l.
3678 18577692 This suggests that, in contrast to glucose, insulin could be involved in the downregulation of plasma adiponectin in insulin-resistant patients.
3679 18591397 Loss of lipin 1 activity causes lipodystrophy and insulin resistance in the fld mouse, and LPIN1 expression and common genetic variation were recently suggested to influence adiposity and insulin sensitivity in humans.
3680 18593820 The present study was undertaken to determine how tumour necrosis factor-alpha (TNF-alpha) elicits the inhibition of glucose-stimulated insulin secretion (GSIS) in rat insulinoma cells (INS)-1 beta-cells.
3681 18599527 Without insulin stimulation, Ad-36 upregulated expressions of several proadipogenic genes, adiponectin, and fatty acid synthase and reduced the expression of inflammatory cytokine macrophage chemoattractant protein-1 in a phosphotidylinositol 3-kinase (PI3K)-dependent manner.
3682 18599621 In conclusion, our findings showed that overnutrition during early life induced obesity and insulin resistance in the adult offspring, and further increased heart size and impaired cardiac insulin signaling, putatively due to an increase in Ptpn1 activity.
3683 18644868 Prep1-hypomorphic (Prep1(i/i)) mice exhibit an absolute reduction in circulating insulin levels but normal glucose tolerance.
3684 18644868 We conclude that Prep1 controls insulin sensitivity through the p160-GLUT4 pathway.
3685 18648765 Neither glucose-stimulated insulin release, insulin content or glucose oxidation were affected by SOCS3.
3686 18657532 Recently, osteocalcin was found to regulate blood glucose, insulin secretion, and fat deposition in mice.
3687 18657616 The combined therapy had a synergic effect on insulin sensitivity when their plasma levels were low (day 6) or high (day 16), that could be associated with Glut-4 plasma membrane content modulation, p85alpha-IRS-1 association and IRS-1 amount.
3688 18664368 Insulin regulates the sub-cellular localization, stability and trans-activation potential of Sp1 by dynamically modulating its post-translational modification by O-linked beta-N-acetylglucosamine (O-GlcNAc) or phosphate residues.
3689 18676184 Impaired clearance has long been invoked to explain this accumulation of intestinal TRLs, but more recent studies have highlighted the fact that the production rate of apolipoprotein (apo) B-48-containing particles is also increased in insulin resistance and Type 2 diabetes.
3690 18680073 Since peroxisome proliferator-activated receptor (PPAR)gamma affects adipocyte differentiation as well as insulin sensitivity, we investigated whether the levels of proinflammatory factors in PCOS patients are related to sequence variations of the PPAR gamma gene.
3691 18704364 Reductions of insulin resistance (measured by homeostasis model assessment of insulin resistance) were independently associated with changes of glucagon, visfatin and PP.
3692 18704364 These results suggest that pancreatic and adipocyte hormones may contribute to the long-term resolution of insulin resistance after RYGBP.
3693 18719127 The islet IL-6R is functional, and IL-6 acutely regulates both pro-glucagon mRNA and glucagon secretion in mouse and human islets, with no acute effect on insulin secretion.
3694 18759508 Pioglitazone is an antidiabetic drug that targets insulin resistance in patients with type 2 diabetes mellitus by stimulating the peroxisome proliferator-activated receptor (PPAR)-gamma.
3695 18556349 Our data show that a 1-month chronic blockage of brain GLP-1 signaling by exendin-9 (Ex9), totally prevented hyperinsulinemia and insulin resistance in HFD mice.
3696 18556349 Thus, we have demonstrated that in response to a HFD, brain GLP-1 signaling induces hyperinsulinemia and insulin resistance and decreases energy expenditure by reducing metabolic thermogenesis and ambulatory activity.
3697 18562232 Changes in the expression of HKII and p85alpha Pi3K were examined as positive controls for the induction of gene expression by the insulin pathway.
3698 18563679 Leptin and adiponectin were independently associated with SI, but not with insulin secretion or beta-cell function.
3699 18566119 In this study, we show that IRE-BP1 interacts with the insulin response sequence of the IGF-I, IGFBP-1, and IGFBP-3 genes using chromatin immunoprecipitation assay.
3700 18566119 Furthermore, activation by IRE-BP1 is sequence specific and mimics that of the insulin effect on gene transcription.
3701 18566119 Tissue expression of IRE-BP1 is 50- to 200-fold higher in classical insulin target compared with nontarget tissues in lean animals, with a significantly reduced level of expression in the skeletal muscle and adipose tissue in obese and diabetic animals.
3702 18596725 ARB treatment significantly improved insulin sensitivity and markedly suppressed AT2-induced oxidative stress, PAI-1 and MCP-1 levels and NF-kappaB activation of adipocytes in culture.
3703 18615583 In human studies, ASP is increased in insulin resistant states such as obesity, diabetes, polycystic ovary syndrome and late pregnancy (the latter two associated with altered sex hormones).
3704 18615583 Sex steroid hormone-induced ASP resistance via C5L2 may contribute to altered adipose tissue function and insulin resistance phenotype in humans.
3705 18638024 Paraventricular nucleus corticotrophin-releasing factor (CRF) mRNA was elevated by STZ treatment, an effect prevented by either insulin treatment or GV.
3706 18638024 Arcuate nucleus neuropeptide Y, but not pro-opiomelanocortin, mRNA expression was elevated by STZ treatment and all vagal manipulations; however, exogenous insulin treatment failed to prevent this, in keeping with their previously documented elevated caloric intake.
3707 18669627 The lipid droplet protein adipose differentiation-related protein (ADRP) mediates hepatic steatosis, but whether this affects insulin action in the liver or peripheral organs in diet-induced obesity is uncertain.
3708 18678273 Inhibition of c-Jun N-terminal kinases by a small cell-permeable peptide improves insulin sensitivity in mice.
3709 18678273 Hepatic inhibition of c-Jun N-terminal kinases using a dominant-negative protein or knockdown of c-Jun N-terminal kinase-1 gene by RNA interference reduces blood glucose and insulin levels and enhances hepatic insulin signaling in mice.
3710 18707891 Further evaluation in cell models illustrated that the derivatives enhanced insulin receptor phosphorylation in CHO/hIR cells and also stimulated glucose uptake in L6 myotubes with or addition of without insulin.
3711 18778119 Somatostatin and its analogues (octreotide and lanreotide) bind to somatostatin subtype 5 receptors on the beta-cell membrane, which limits insulin release and, consequently, may decrease adipogenesis.
3712 18778119 In conclusion, somatostatin and its analogues, by suppressing beta-cell insulin secretion, can retard weight gain in children with hypothalamic obesity and induce a small amount of weight loss in some adults with hyperinsulinaemic obesity.
3713 18779578 Up-regulation of insulin-like growth factor 1 (IGF-1) expression and plasma levels and increasing IGF-1 receptor phosphorylation in muscle may explain the increased insulin receptor substrate 1, PI3K, and ERK phosphorylation in skeletal muscle.
3714 18780892 Pharmacological and genetic analyses of p110beta function revealed that p110beta catalytic activity is required for PI3K signaling downstream of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors as well as to sustain long-term insulin signaling.
3715 18792873 Our present study suggests that PEDF could improve the AGE-elicited insulin resistance in Hep3B cells by inhibiting JNK- and IkappaB kinase-dependent serine phosphorylation of IRS-1 via suppression of Rac-1 activation.
3716 18792876 In the first part of this paper, we review clinical studies to support the concept that angiotensin II type 1 receptor blockers (ARBs) could prevent the development of AF in insulin resistant patients and discuss the possible underlying mechanisms.
3717 18792879 More studies are required in order to certify the role of NOS inhibitors in insulin resistance and endothelial dysfunction.
3718 18034843 We also investigated the in vitro efficacy of a glucokinase activator (GKA) on glucose-stimulated insulin secretion (GSIS) in gk(del/wt)mouse islets.
3719 18034844 Insulin has both a vasodilatory effect, which is largely endothelium dependent through the release of nitric oxide, and a vasoconstrictory effect through the stimulation of the sympathetic nervous system and the release of endothelin-1.
3720 18565135 Adipokines, specifically adiponectin and resistin, are secreted from adipocytes and are thought to cause insulin resistance in rodents.
3721 18566293 Using a hyperinsulinemic clamp in young rats, we show that experimental activation of HBP, through the systemic infusion of glucosamine, induced severe insulin resistance (36% decline in peripheral insulin action; P<0.05), increased adipose tissue gene expression of fat-derived peptides (PAI-1 by 4-fold, angiotensinogen 3-fold, leptin 2-fold, resistin 4-fold, and adiponectin 4-fold; P<0.01 compared with young saline-infused), and enhanced glycosylation of transcription factors, thus mimicking a physiological and biological phenotype of aging.
3722 18591391 Associations with 2-h glucose, insulin, and HOMA-IR remained significant after further adjustment for IGF-1, parathyroid hormone, calcium, physical activity, and social class.
3723 18591395 We used insulinoma-1E cells to analyze the effects of miR-375 on PDK1 protein level and downstream signaling using Western blotting, glucose-induced insulin gene expression using quantitative RT-PCR, and DNA synthesis by measuring thymidine incorporation.
3724 18591395 We found that miR-375 directly targets PDK1 and reduces its protein level, resulting in decreased glucose-stimulatory action on insulin gene expression and DNA synthesis.
3725 18591395 The effects of glucose on miR-375 are compatible with the idea that miR-375 is involved in glucose regulation of insulin gene expression and beta-cell growth.
3726 18599523 Serum insulin levels were significantly decreased in animals lacking endocrine cell survivin, with relative stability of other hormones.
3727 17949249 Renal cortical activity and expression of Akt and mTOR (kinase assay, western blotting) were determined in streptozotocin-diabetic rats (D) with different levels of glycemic control (blood glucose 22.0+/-1.0, 13.4+/-1.5, 8.1+/-0.4 mmol/l, p<0.05 between the groups), achieved by varying insulin treatment (0, 4 and 12 IU/day), and in control rats with (C4) or without (C) chronic insulin administration.
3728 17949249 Renal Akt activity was reduced in D rats without insulin treatment and severe hyperglycemia (D-0, -62 %, p<0.01 vs.
3729 17949249 Moreover, insulin activated renal Akt (+82 %, p<0.01), but not mTOR in C4.
3730 18363889 Total and HMW plasma adiponectin correlated with clinical and biochemical measures of insulin sensitivity.
3731 18363889 Plasma adiponectin and skeletal muscle AdipoR2 mRNA expression are reduced in subjects with diabetes; both are likely to contribute to the observed insulin resistance.
3732 18053093 However, the role of EGF in regulating the major function of the pancreas, insulin secretion, has not been studied.
3733 18053093 Here, we show that EGF rapidly increased insulin secretion in mouse pancreatic islets, as well as in a pancreatic beta-cell line.
3734 18053093 In addition, EGF also increased plasma insulin levels and mediated glucose lowering in normal and diabetic mice.
3735 18662725 At high glucose the impaired glucose-stimulated insulin release was associated with an increased iNOS expression and activity and NOS inhibition dose-dependently amplified insulin secretion in both GK and control islets.
3736 18691554 Using a fluorescent assay based upon a novel pseudo-substrate of PDI, flow cytometry and immunological techniques, we have demonstrated the presence of PDI on the surface of pMP (termed msPDI) and its ability to influence insulin-mediated Akt phosphorylation (Thr308) in 3T3-L1 fibroblasts.
3737 18691554 Moreover, pMP are shown to contain catalytically active PDI, capable of both promoting platelet aggregation and disrupting insulin signaling. pMP increased initial rates of aggregation by 4-fold and the pro-aggregatory activity of pMPs could be attenuated with an anti-PDI antibody.
3738 18776135 These studies demonstrate in a variety of rodent models that systemic delivery of Kir6.2/SUR-1-selective KCOs enhance the glucose counterregulatory response to insulin-induced hypoglycemia.
3739 18776138 We aimed to study direct effects of ghrelin on substrate metabolism and insulin sensitivity in human subjects.
3740 18776138 In the absence of GH and cortisol secretion, ghrelin acutely decreased peripheral, but not hepatic, insulin sensitivity together with stimulation of lipolysis.
3741 18776138 Ghrelin infusion acutely induces lipolysis and insulin resistance independently of GH and cortisol.
3742 18787058 The aims of the present study were to investigate the expression of toll-like receptor 2 (TLR2) in muscle and white adipose tissue (WAT) of diet-induced obesity (DIO) mice, and also the effects of its inhibition, with the use of TLR2 antisense oligonucleotide (ASON), on insulin sensitivity and signaling.
3743 18796617 Three mechanisms seem to operate in IL-6-induced insulin resistance: activation of c-Jun NH(2)-terminal kinase 1/2 (JNK1/2), accumulation of suppressor of cytokine signaling 3 (socs3) mRNA, and an increase in PTP1B activity.
3744 18796617 Finally, the lack of PTP1B confers protection against IL-6-induced insulin resistance in skeletal muscle in vitro and in vivo, in agreement with the protection against the IL-6 hyperglycemic effect observed on glucose and insulin tolerance tests in adult male mice.
3745 18801932 Insulin-stimulated translocation of the glucose transporter GLUT4 to the plasma membrane in muscle and fat cells depends on the phosphatidylinositide 3-kinase/Akt pathway.
3746 18801932 The downstream target AS160/TBC1D4 is phosphorylated upon insulin stimulation and contains a TBC domain (Tre-2/Bub2/Cdc16) that is present in most Rab guanosine triphosphatase-activating proteins.
3747 18801932 Whereas the insulin-dependent dissociation of TBC1D4 from membranes was not required for GLUT4 translocation, its phosphorylation was essential.
3748 18809626 The objectives of this study were to determine age- and sex-specific concentrations of adiponectin in Asian Indian teenagers and adults and to assess whether its blood levels correlated with insulin resistance and other cardiometabolic parameters.
3749 18829990 Diabetic rats were treated with insulin, candesartan (ARB), benazepril (ACE inhibitor), or aliskiren (renin inhibitor).
3750 18835930 The GLP-1 and gastrin combination increased pancreatic insulin content, beta-cell mass, and insulin-positive cells in pancreatic ducts, and beta-cell apoptosis was decreased.
3751 18835937 In this study, we have investigated the effects of Pref-1 overexpression on whole-body glucose homeostasis and its contribution to the development of insulin resistance.
3752 18845673 Glucose-stimulated insulin secretion was unaffected by CCK expression.
3753 18925540 Insulin stimulation of fibroblasts with mutations resulted in a significantly smaller increase in PTP1B activity compared with stimulation of wild-type fibroblasts (p<0.05).
3754 18929539 Thus, reducing SOCS expression could prevent the development of obesity-induced insulin resistance.
3755 18929539 HFD also induced hyperglycemia in SOCS-1 deficient mice with impairment of glucose and insulin tolerance tests.
3756 18929539 Thus, despite the role of SOCS proteins in obesity-related insulin resistance, SOCS-1 deficiency alone is not able to prevent insulin resistance induced by a diet rich in fat.
3757 18948074 However, staurosporine, JNK, and calmodulin kinase have different effects on the induction of insulin expression.
3758 18951876 In this study, human insulin promoter was activated by Smad2, Smad3 and the pancreatic and duodenal homeobox factor-1 (PDX-1) in the ALK7 pathway.
3759 18951876 These results indicate that one of the direct target genes of Nodal and Activin AB signals is the insulin gene in pancreatic beta-cells and that PDX-1 is directly involved in the ALK7-Smad pathway.
3760 18973876 Insulin phosphorylated its receptor in the neuroblastoma cells but not in astrocytes and, like IGF-1, increased ERK1/2 and Akt phosphorylation.
3761 18980783 In this randomized, placebo-controlled, double-blind study of 57 abdominally obese middle-aged men, conjugated linoleic acid (CLA) did not induce changes in retinol-binding protein 4 concentrations (RBP4), despite marked induced insulin resistance.
3762 18987435 A high concentration of GLP-1 (10 nM) stimulated intracellular cAMP accumulation and insulin secretion was significantly inhibited by KT5720, a selective inhibitor of PKA.
3763 18987435 Insulin secretion stimulated by 1 pM GLP-1 was reduced by inhibitors of calcium action, including verapamil, dantrolene, and BAPTA.
3764 19007436 In addition, a defect in insulin secretion could occur due to UPS-mediated degradation of IRS2 in the beta-cells of the pancreas.
3765 19008912 Insulin directly increased STAT5 and SOCS2 expression in mesangial cells.
3766 19008912 This study shows that insulin can inhibit the mitogenic action of IGF-1 in mesangial cells by regulating STAT5/SOCS2 expression.
3767 19011089 DsbA-L expression in 3T3-L1 adipocytes is stimulated by the insulin sensitizer rosiglitazone and inhibited by the inflammatory cytokine TNFalpha.
3768 19011670 Although ramipril also reversed high blood pressure, it had a lesser effect on insulin resistance (including IRS-1) and blocked superoxide anion production only in aorta.
3769 19011679 Insulin stimulated expression of aPKCzeta (p<0.001) and Akt1 (p<0.001) was decreased in muscle of LBW men when compared to insulin stimulated controls.
3770 19021703 The study was performed to determine whether sucrose-induced insulin resistance could increase the expression of cardiac matrix metalloproteinases (MMPs), indices of matrix remodelling, and whether the addition of 1.25 g day(-1) of L-arginine (ARG) to a sucrose diet could prevent both the sucrose-induced metabolic abnormalities and elevated cardiac expression of matrix metalloproteinases in an insulin resistant stage that precedes frank type 2 diabetes.
3771 19022947 In contrast to CRP and TNFalpha, adiponectin increases during weight loss and insulin sensitivity.
3772 19023081 In mouse models of insulin-deficient diabetes, liver-selective activation of ERK signaling increased beta cell mass and normalized serum glucose levels.
3773 19024311 It is fasting ghrelin not PYY negatively associated with fasting insulin and positively with QUICKI.
3774 19029977 The systolic blood pressure and endothelin-1-induced contractile responses in aortae in vitro were enhanced in insulin-treated diabetic rats and blunted by chronic losartan administration.
3775 19029977 ET(A) and ET(B) receptors, ERK-1/2 and MEK-1/2 protein expression and endothelin-1-stimulated ERK phosphorylation were all increased in aortae from insulin-treated diabetic rats.
3776 19029977 These results suggest that the combination of high plasma angiotensin II and insulin with a diabetic state induced enhancement of endothelin-1-induced vasoconstriction, ET(A) receptor expression and ERK expression/activity in the aorta.
3777 19031217 To investigate changes in serum adiponectin during pregnancy and postpartum and assess its relationship with insulin resistance as measured by homeostasis model assessment (HOMA-IR).
3778 18178198 These data suggest that GSK3beta is hyperactivated and resistant to down-regulation by insulin in PCOS.
3779 18284435 Plasma adiponectin correlated with insulin-stimulated Rd, non-oxidative glucose disposal (NOGD), glucose storage and SI in both groups after adjustment for sex and body fat.
3780 18284435 In FDR, plasma adiponectin correlated with insulin-stimulated glycogen synthase activity and the troglitazone-induced increase in plasma adiponectin correlated with the improvement in insulin-stimulated Rd and SI after adjustment for sex and body fat.
3781 18435775 In humans, GLP-1 stimulates insulin secretion and inhibits glucagon and gastrointestinal secretions and motility.
3782 18654034 SNP rs1884614 in the P2 promoter region of the HNF-4alpha gene may influence insulin secretion in non-obese Japanese subjects with type 2 diabetes.
3783 19014491 Multivariate regressions analyses with adjustment for relevant covariates were performed to detect associations of SIRT1 variants with the changes in anthropometrics, weight, body fat or metabolic characteristics (blood glucose, insulin sensitivity, insulin secretion and liver fat, measured by magnetic resonance techniques) after the 9-month follow-up test in the TULIP study.
3784 19074620 GLP-1, on the other hand, is still insulinotropic in T2DM, and this has led to the development of compounds that activate the GLP-1 receptor with a view to improving insulin secretion.
3785 19086646 Puerarin can decrease the blood glucose level of T2DM by downregulating ADRP mRNA expression and depressing the insulin resistance.
3786 19094928 These anti-inflammatory and anti-catabolic properties were confirmed in animal models of joint diseases where PPAR agonists reduced synovial inflammation while preventing cartilage destruction or inflammatory bone loss, although many effects required much higher doses than needed to restore insulin sensitivity or to lower circulating lipid levels.
3787 19108709 Insulin-induced increases in c-Jun NH2-terminal kinase-1 (JNK1) activity were partially inhibited by m7E3 and eptifibatide whereas antagonism of alphavbeta3 integrins had no effect on insulin-induced increases in extracellular signal-regulated kinase (ERK) activity.
3788 19109737 Treatment with high glucose alone (HG) or GI but not HI (high insulin alone) decreased EPC proliferation and their expression of cyclin E, cdk2 and PCNA compared to control.
3789 19114996 Because insulin resistance is characterized by a marked reduction in insulin-stimulated PI3K-mediated activation of Akt, we asked whether MES could increase Akt phosphorylation and ameliorate insulin resistance.
3790 19120312 In contrast, stimulation with insulin tended to induce high FOXP3 mRNA expression in T1D children compared to reference children (P= 0.057).
3791 19125180 The corresponding plasma resistin levels were slightly, but not significantly, increased in DM2 women (P = .051), and overall, they correlated significantly with BMI (r = 0.406, P = .010) and waist circumference (r = 0.516, P = .003), but not with fasting insulin levels or HOMA-IR.
3792 19132222 Especially a defective insulin response in the liver contributes to the development of hyperglycemia, dyslipidemia and peripheral insulin resistance and may contribute to hepatic over-expression of PAI-1 in diabetes type 2.
3793 19136982 We have found that decreased high molecular weight (HMW) adiponectin plays a crucial and causal role in obesity-linked insulin resistance and metabolic syndrome; that AdipoR1 and AdipoR2 serve as the major AdipoRs in vivo; and that AdipoR1 activates the AMP kinase (AMPK) pathway and AdipoR2, the peroxisome proliferator-activated receptor alpha (PPARalpha) pathway in the liver, to increase insulin sensitivity and decrease inflammation.
3794 19136982 Further conclusions are that decreased adiponectin action and increased monocyte chemoattractant protein-1 (MCP-1) form a vicious adipokine network causing obesity-linked insulin resistance and metabolic syndrome; PPARgamma upregulates HMW adiponectin and PPARalpha upregulates AdipoRs; that dietary osmotin can serve as a naturally occurring adiponectin receptor agonist; and finally, that under starvation conditions, MMW adiponectin activates AMPK in hypothalamus, and promotes food intake, and at the same time HMW adiponectin activates AMPK in peripheral tissues, such as skeletal muscle, and stimulates fatty-acids combustion.
3795 19136982 Importantly, under pathophysiological conditions, such as obesity and diabetes, only HMW adiponectin was decreased; therefore, strategies to increase only HMW adiponectin may be a logical approach to provide a novel treatment modality for obesity-linked diseases, such as insulin resistance and type 2 diabetes.
3796 19138973 Treating these mice with EGCG also caused an increase in the serum level of IGFBP-3 while conversely decreasing the serum levels of IGF-I, insulin, triglyceride, cholesterol, and leptin.
3797 19159557 To investigate the effect of early insulin therapy on the nuclear factor kappaB (NF-kappaB) pathway and inflammatory cytokine responses in skeletal muscle in type 2 diabetes mellitus (DM).
3798 19159557 Early treatment of insulin and gliclazide increased the IkappaBalpha protein expression, decreased the NF-kappaB P65 DNA binding activity and the TNF-alpha expression in the skeletal muscle.
3799 19160530 On univariate analysis, angiogenin was positively associated with age, plasma glucose, insulin, and BNP (all P < 0.001); and negatively correlated with diastolic blood pressure (P = 0.04) and EF (P = 0.002).
3800 19170358 Besides classical sulfonylureas and glinides, new insulin secretagogues are now available, which target the incretin gut hormone glucagon-like peptide-1 (GLP-1).
3801 18266981 Homeostasis of blood glucose by insulin involves stimulation of glucose uptake by translocation of glucose transporter Glut-4 from intracellular pool to the caveolar membrane system.
3802 18266981 Our results suggests that the effect of RSV is non-insulin dependent and triggers some of the similar intracellular insulin signalling components in myocardium such as eNOS, Akt through AMPK pathway and also by regulating the caveolin-1 and caveolin-3 status that might play an essential role in Glut-4 translocation and glucose uptake in STZ- induced type-1 diabetic myocardium.
3803 18535489 At 6 wk of development (wd) insulin promoting factor 1 (IPF1) was expressed in the majority of epithelial cells forming tubular structures while GR was present in the mesenchyme, suggesting an early role of glucocorticoids, before endocrine and exocrine differentiation.
3804 18535489 The first insulin cells did not express IPF1 or GR.
3805 18672033 These data suggest that (1) recurrent hypoglycemia, much like uncontrolled diabetes, has a pronounced effect on hippocampal mineralocorticoid receptor mRNA expression that may prevent it, and presumably also the stress axis, from responding properly to a subsequent bout of hypoglycemia, and (2) while long-term insulin treatment was sufficient to restore some of these responses in diabetic animals, tighter glycemic control may be necessary to see full restoration of the stress response.
3806 19011998 The observations in our study suggest the idea that during diabetic hypothyroidism, without thyroid hormone treatment, insulin is not sufficient to balance the metabolic pathways so mediated effects of insulin in leptin regulation via thyroid hormones are an increased possibility.
3807 19195630 Recent experimental and clinical data indicate that peripheral activation of cannabinoid CB1 receptors promotes insulin resistance and liver steatogenesis, two key steps in the pathogenesis of non-alcoholic fatty liver disease.
3808 19195631 Notably, FXR activation inhibits hepatic de novo lipogenesis, increases insulin sensitivity and protects hepatocytes against bile acid-induced cytotoxicity.
3809 19203096 We therefore examined the response of peripheral blood CD8 T cells from new-onset T1DM patients and control subjects possessing HLA-A*0201 genes to potential CD8 T cell epitopes contained in a panel of peptides derived from proinsulin, glutamic acid decarboxylase, islet-specific glucose-6-phosphatase catalytic subunit-related protein and islet amyloid polypeptide, each putatively presented by the HLA class I molecule, HLA-A2.1 (A*0201) using a variety of techniques including in vitro culture with peptide, enzyme-linked immunospot (ELISPOT) assay and HLA tetramers.
3810 19203097 Examples of the former include agents such as GLP1 receptor agonists or DPPIV inhibitors which increase beta cell insulin content.
3811 19231904 Among the aggregate sample, 74% of patients were receiving oral antidiabetics, 26% were receiving insulin, 43% were receiving ACE inhibitors and 50% were receiving antihyperlipidaemics/HMG-CoA reductase inhibitors (statins) during the first 12 months following the index complication.
3812 19246967 We have demonstrated that 3-phosphoinositide-dependent protein kinase 1 (PDK1) contributes to signaling by insulin or insulin-like growth factor-1 (IGF-1) that is responsible for the regulation of both the number and size of pancreatic beta cells in mice.
3813 19258740 Forced expression of STAT3 reduced blood glucose and plasma insulin concentrations as well as the hepatic abundance of mRNA for phosphoenolpyruvate carboxykinase.
3814 19258741 It is established that wortmannin which completely inhibits class IA PI 3-kinase activation abrogated the insulin-dependent translocation of GLUT4 to the plasma membrane in adipocytes and skeletal muscle.
3815 19284081 We shall review the mechanisms by which obesity-related insulin resistance may be associated with fibrosis extension and decreased efficacy of IFN-alpha based therapies in obese individuals with chronic hepatitis C and the therapeutic strategies that may increase the effectiveness of these therapies.
3816 19330070 The critical initial steps in insulin action include phosphorylation of adapter proteins and activation of phosphatidylinositol 3-kinase (PI3K).
3817 19330070 The work of numerous different researchers indicates a role of PKB in regulating insulin-stimulated glucose uptake.
3818 19337387 We studied the efficacy of salsalate in reducing glycemia and insulin resistance and potential mechanisms of action to validate NF-kappaB as a potential pharmacologic target in diabetes.
3819 19378424 To examine the hypothesis that serum concentration of C-reactive protein (CRP) is inversely associated with insulin sensitivity and obesity, and that this may by mediated by tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6).
3820 19378424 CRP was inversely associated with insulin sensitivity (r = -0.28, p < 0.01) and with total body fat (r = 0.31, p < 0.01), but not independently of the TNFalpha and sTNFAR2 product.
3821 19378424 Serum CRP, TNFalpha, sTNFAR2, but not IL-6, were associated with low insulin sensitivity, total body fat, abdominal obesity, hyperinsulinemia, hypertriglyceridemia, low HDL cholesterol and small LDL particles, i.e. the metabolic syndrome.
3822 19885208 In long-term glycemic control, the AC protocol significantly decreased hemoglobin A1c in conditions of suboptimal basal insulin replacement for SMBG frequencies > or = 6/day, and reduced the occurrence of mild and severe hypoglycemia by 86-100% over controls, over all SMBG frequencies in conditions of optimal basal insulin.
3823 20161845 Glucokinase (GK) is expressed in multiple organs and plays a key role in hepatic glucose metabolism and pancreatic insulin secretion.
3824 18466348 However, the altered activity of the ADIPOR1 promoter was associated with insulin resistance and SNPs of ADIPOR2 were associated with waist circumference.
3825 18466349 These data demonstrate that RBP4 in cirrhosis (i) is decreased due to reduced hepatic production, (ii) is not associated with insulin resistance, and (iii) might have a beneficial role by decreasing hepatic glucose production and could thus also be regarded as a hepatokine.
3826 17768029 Alloxan-induced diabetes is thus a multifactor-promoted diabetes model which still could be used to examine the antidiabetic effects of compounds prompting insulin secretion and increasing liver-specific glucokinase activity.
3827 18952711 Serum insulin-like growth factor (IGF) -1 is secreted mainly by the liver and circulates bound to IGF-binding proteins (IGFBPs), either as binary complexes or ternary complexes with IGFBP-3 or IGFBP-5 and an acid-labile subunit (ALS).
3828 18979373 Correction of the metabolic derangement with insulin decreased excretion of albumin and TGF-beta(1), but had no effect on kidney size and urine NC1 excretion, presumably because the observation period was too short.
3829 18984030 Glucocorticoids chronically increase palatable food intake, which increases abdominal fat depots and circulating insulin levels, both of which negatively correlate with PVN CRF mRNA expression and may in turn dampen the response to stress.
3830 19013780 Adiponectin is positively correlated with insulin sensitivity.
3831 19029027 Protein-tyrosine phosphatase-1B (PTP1B) has been implicated in the negative regulation of insulin signaling.
3832 19033408 Whereas physical activity did not correlate with insulin resistance (r = -0.01), leptin (r = +0.04), or hsCRP (r = +0.01) independently of percent body fat, it did correlate with adiponectin, but inversely (r = -0.18, P = 0.02).
3833 19046915 A common functional ENPP1 K121Q polymorphism has been suggested to contribute to insulin resistance, obesity and type 2 diabetes (T2D) in various ethnic groups.
3834 19073766 Heat treatment resulted in decreased activation of Jun NH2-terminal kinase (JNK) and inhibitor of kappaB kinase (IKK-beta), stress kinases implicated in insulin resistance, and upregulation of HSP72 and HSP25, proteins previously shown to inhibit JNK and IKK-beta activation, respectively.
3835 19073770 Silencing of phogrin in beta-cells abrogated the glucose-mediated mitogenic effect, which was accompanied by a reduction in the level of insulin receptor substrate 2 (IRS2) protein, without any changes in insulin secretion.
3836 19073770 We propose that phogrin and IA-2 function as an essential regulator of autocrine insulin action in pancreatic beta-cells.
3837 19073774 We hypothesized that skeletal muscle-specific overexpression of the muscle isoform of carnitine palmitoyltransferase 1 (CPT1), the enzyme that controls the entry of long-chain fatty acyl CoA into mitochondria, would enhance rates of fatty acid oxidation and improve insulin action in muscle in high-fat diet insulin-resistant rats.
3838 19074988 The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling; consequently, mice deficient in PTP1B are hypersensitive to insulin.
3839 19074988 Liver-specific PTP1B(-/-) mice have increased hepatic insulin signaling, decreased expression of gluconeogenic genes PEPCK and G-6-Pase, enhanced insulin-induced suppression of hepatic glucose production, and improved glucose tolerance.
3840 19081082 Ang II activates NAD(P)H oxidase in several tissues with important function in the control of insulin secretion.
3841 19097921 We recently reported that rs361072, a promoter C/T variant of p110beta, the catalytic subunit of PI3-kinase, was associated with a protection from insulin resistance (IR) in Caucasian adolescents in proportion of their body mass.
3842 19103594 Treatment of cells with 25 mm glucose for 24-48 h decreased insulin mRNA and protein levels and reduced the proinsulin translation rate, which was accompanied by enhanced unfolded protein response pathway activation (XBP-1 mRNA splicing and increased phospho-eIF2alpha, CHOP, and active ATF6 levels).
3843 19103594 Overexpressing the ER chaperone GRP78 partially rescued high glucose-induced suppression of proinsulin levels and improved glucose-stimulated insulin secretion with no effect on insulin 2 mRNA levels.
3844 19103594 Knockdown of GRP78 expression under basal glucose conditions reduced cellular insulin levels and glucose-stimulated insulin secretion.
3845 19121967 Quantitative PCR (qPCR) confirmed the differential expression of genes including glycerol kinase (Gyk), phosphatidylinositol 3-kinase regulatory subunit, polypeptide 1 (p85 alpha) (Pik3r1), insulin-like growth factor 1 (Igf1), and growth factor receptor bound protein 2-associated protein 1 (Gab1).
3846 19122171 Thus we hypothesized that regulation of IGF1R expression may impact cellular insulin sensitivity.
3847 19122171 Conversely, IGF1R downregulation by siRNA allowed assembly of insulin holoreceptors, enhanced insulin-induced phosphorylation of its receptor, Akt, Erk1/2, and further augmented insulin-induced glucose uptake.
3848 19122171 IGF1R downregulation uncovered an insulin-induced reduction in activation of NF-kappaB and inhibition of MCP-1 upregulation in response to TNF-alpha.
3849 19122171 Downregulation of IGF1R increases the fraction of insulin receptors organized in holoreceptors, which leads to enhanced insulin signaling and unmasks potential antiinflammatory properties of insulin in VSMCs.
3850 19126543 Resistin antagonizes insulin action in mouse, making it a potential therapeutic target for treating metabolic diseases such as diabetes.
3851 19131512 Pancreata from CTGF null embryos have an increase in glucagon(+) cells with a concomitant decrease in insulin(+) cells, and show defects in islet morphogenesis.
3852 19148619 After 48 h, amyloid deposition was associated with increased ROS levels and increased beta cell apoptosis, but no change in insulin secretion, content or mRNA levels.
3853 19148619 Inhibition of amyloid formation also increased insulin content.
3854 19154729 S-nitrosylation of IDE enzyme did not affect the insulin degradation products produced by the enzyme, nor did NO affect insulin binding to IDE as determined by cross-linking studies.
3855 19164337 Fasting serum IGFBP-1, fasting plasma insulin (FPI), homeostasis model assessment (HOMA-IR), quantitative insulin check index (QUICKI), fasting glucose to insulin ratio (FGIR), Raynaud and insulin glycaemic index (ISI-gly) were correlated with FSIVGTT (Si) in 22 subjects with normal glucose tolerance (NGT) and nine with impaired fasting glucose (IFG).
3856 19169663 In this model mouse mimicking human type 2 diabetes (STZ/HFD), continuous leptin infusion reduced food intake and body weight and improved glucose and lipid metabolism with enhancement of insulin sensitivity.
3857 19169664 Following pioglitazone, insulin-stimulated glucose disposal increased by 30% (p < 0.01), and muscle AMPK and acetyl-CoA carboxylase (ACC) phosphorylation increased by 38% and 53%, respectively (p < 0.05).
3858 19171794 HO-1 induction improved hyperinsulinemia and insulin sensitivity in ZDF rats.
3859 19181734 We reviewed pharmacological and genetic alterations of FASN activity that have been shown to significantly influence energy expenditure rates, fat mass, insulin sensitivity, and cancer risk.
3860 19190890 We studied the effect of breeding Wfs1 ( -/- ) mice on a C57BL/6J background with mild obesity and insulin resistance, by introducing the agouti lethal yellow mutation (A ( y ) /a).
3861 19214472 In contrast, adding insulin to the culture medium or stimulating insulin secretion with different secretagogues suppressed TXNIP.
3862 19214472 Inhibition of glucose and fatty acid-stimulated insulin secretion with diazoxide increased TXNIP production in beta cells.
3863 19214472 Nitric oxide (NO), a repressor of TXNIP, enhanced insulin signal transduction, whereas inhibition of NO synthase abolished its activation, suggesting that TXNIP inhibition by NO is mediated by stimulation of insulin signalling.
3864 19214472 Insulin is a potent repressor of TXNIP, operating a negative feedback loop that restrains the stimulation of TXNIP by chronic hyperglycaemia.
3865 19218147 Akt is also a factor in the pathomechanism of diabetes as it determines beta-cell apoptosis of Langerhans islets and insulin sensitivity of the cells.
3866 19232040 In animal models of DM, pharmaceutical inhibition of SGLT2 reduces hyperglycaemia, and may improve insulin resistance.
3867 19236623 To assess the association of insulin resistance with increased urinary albumin excretion (UAE) in a cohort of Iranian Type 2 diabetic patients.
3868 19082668 Ghrelin treatment increased insulin levels, insulin-positive islet cell number, and 5-bromo-2-deoxyuridine and PDX-1 staining, whereas ghrelin antagonist administration resulted in significant decreases in these parameters.
3869 19106228 Interestingly, in hemin-treated ZDF, inhibitory proteins of insulin-signaling, such as glycogen synthase kinase-3 and protein-tyrosine phosphatase-1B were reduced, whereas agents that promote insulin signaling including adiponectin, cAMP, AMP-activated protein kinase, aldolase-B, and glucose transporter-4 (GLUT4), were robustly increased.
3870 19106228 Correspondingly, hemin improved ip glucose tolerance, reduced insulin intolerance, and lowered insulin resistance (homeostasis model assessment of insulin resistance), and the inability of insulin to enhance GLUT4 was overturned.
3871 19141606 In patients with HO and SHO: i) insulin resistance was comparable; ii) insulin-stimulated rates of glucose transport in isolated monocytes were decreased due to impaired translocation of GLUT4 glucose transporters on the plasma membrane; iii) these findings could justify the increased risk for insulin resistance-associated disorders, such as cardiovascular disease, observed in patients with HO or SHO.
3872 19165156 Peroxisome proliferator-activated receptor gamma (PPARgamma) acts as a ligand-dependent transcription factor with a key role in mediating adipocyte differentiation and insulin sensitivity.
3873 19188424 Protein interaction studies used subcellular fractions and detergent lysates prepared from MIN6 beta-cells to determine the mechanistic role of Munc18c in Syntaxin 4 activation and docking/fusion of vesicle-associated membrane protein (VAMP)2-containing insulin granules.
3874 19188424 Munc18c depletion ablated the glucose-stimulated VAMP2-Syntaxin 4 association as well as Syntaxin 4 activation, correlating with the deficit in insulin release.
3875 19188427 The cytokine interleukin-6 (IL-6) stimulates AMP-activated protein kinase (AMPK) and insulin signaling in skeletal muscle, both of which result in the activation of endothelial nitric oxide synthase (eNOS).
3876 19188427 IL-6 blunted increases in insulin signaling, eNOS phosphorylation (Ser1177), and NO production and reduced phosphorylation of AMPK in HAEC in vitro and capillary recruitment in vivo.
3877 19188427 The differences in endothelial cell and skeletal muscle signaling were mediated by the cell-specific, additive effects of IL-6 and insulin because this treatment markedly increased tumor necrosis factor (TNF)-alpha protein expression in HAECs without any effect on TNF-alpha in skeletal muscle.
3878 19188427 In the presence of insulin, IL-6 contributes to aberrant endothelial cell signaling because of increased TNF-alpha expression.
3879 19196890 SHBG was significantly positively associated with insulin sensitivity in boys (P < 0.001) and girls (P < 0.001).
3880 19208858 The reduction of hyperglycemia was accompanied by enhanced HO-1, HO activity, and cGMP of the soleus muscle, alongside increased plasma bilirubin, ferritin, SOD, total antioxidant capacity, and insulin levels, whereas markers/mediators of oxidative stress like urinary-8-isoprostane and soleus muscle nitrotyrosine, NF-kappaB, and activator protein-1 and -2 were abated.
3881 19208858 Furthermore, inhibitors of insulin signaling including soleus muscle glycogen synthase kinase-3 and JNK were reduced, while the insulin-sensitizing adipokine, adiponectin, alongside AMPK were increased.
3882 19208898 A similar treatment with pioglitazone (0.03%), an insulin sensitizer, did not affect plasma DPP-4 activity or GLP-1 levels.
3883 19208906 Ablating myostatin (Mstn) prevents obesity, so we investigated if Mstn deficiency could improve insulin sensitivity.
3884 19208906 Improvements to muscle and liver insulin sensitivity (approximately 200-400%) correlated with 50-75% decreased tumor necrosis factor (TNF)alpha production and coincided with severe Mstn deficiency.
3885 19208906 Short-term treatment of Mstn(Ln/Ln) mice with recombinant Mstn led to increased plasma TNFalpha and insulin resistance.
3886 19208910 There was good selection of CD8 T-cells with a predominance of CD8 single-positive thymocytes, in spite of thymic insulin expression.
3887 19208911 These data suggest that 1) insulin stimulates glucose transport and phosphorylation of AS160 and TBC1D1 in a PI 3-kinase/Akt-dependent manner, 2) contraction stimulates PAS-AS160 (but not PAS-TBC1D1 or glucose transport) in a PI 3-kinase/Akt-dependent manner, and 3) contraction stimulates PAS-TBC1D1 and glucose transport (but not PAS-AS160) in an AMPK-dependent manner.
3888 19208912 Application of OEA (10 micromol/l) directly into the rat ileum, but not intravenously, increased plasma bioactive GLP-1 levels in euglycemic animals by 1.5-fold (P < 0.05) and insulin levels by 3.9-fold (P < 0.01) but only in the presence of hyperglycemia.
3889 19208914 To test the hypotheses that decreased insulin-mediated glucose disposal in muscle is associated with a reduced muscle microvascular exchange capacity (Kf) and that 6 months of high-dose statin therapy would improve microvascular function in people with central obesity.
3890 19221053 These findings indicate that MOR-1 regulates body weight by a mechanism that involves insulin secretion and thus may represent a novel target for new diabetes therapies.
3891 19223652 This change in the glucose sensitivity in the presence of insulin was reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (10 nM) but not by the mitogen-activated kinase (MAPK) inhibitor PD-98059 (PD; 50 microM).
3892 19228796 Serum insulin and pancreatic insulin content were reduced in LP-fed NOD offspring at 8 weeks, as were serum interferon gamma and pancreatic tumor necrosis factor alpha, while the number of pancreatic islets demonstrating peri-insulitis, and the degree of invasiveness were reduced.
3893 19251743 In addition, angiotensin (Ang) II is able to induce insulin resistance and an inflammatory state through Ang II receptor type 1 (AT1R).
3894 19251743 Accordingly, we examined whether inhibition of AT1R with irbesartan (IRB) can protect against the development of insulin resistance in obese Zucker rats (OZRs).
3895 19251743 Taken together, these findings suggest that TBK1 could be involved in the insulin resistance mechanism related with IR Ser994 phosphorylation in a genetic model of diabetes.
3896 19265200 Here, we define an important role of the TGF-beta pathway in regulation of insulin gene transcription and beta-cell function.
3897 19265200 Transduction of adenoviral Smad3 into primary human and non-human primate islets suppresses insulin content, whereas, dominant-negative Smad3 enhances insulin levels.
3898 19276091 Rho-kinase (ROCK) isoforms have been shown to participate in insulin signaling and glucose metabolism in cultured cell lines.
3899 19276091 To investigate the physiological role of ROCK1 in the regulation of whole body glucose homeostasis and insulin sensitivity in vivo, we studied mice with global disruption of ROCK1.
3900 19276091 Insulin-stimulated phosphatidylinositol 3-kinase activity associated with IRS-1 or phospho-tyrosine was also reduced approximately 40% without any alteration in tyrosine phosphorylation of insulin receptor in skeletal muscle.
3901 19276091 Thus, our results identify ROCK1 as a novel regulator of glucose homeostasis and insulin sensitivity in vivo, which could lead to new treatment approaches for obesity and type 2 diabetes.
3902 19279289 In contrast, plasma leptin was only increased by insulin and diet, plasma glucagon and liver glycogen was only affected by insulin and liver triglycerides, and arcuate nucleus proopiomelanocortin mRNA was only influenced by diet.
3903 19292763 Human CD4(+) T cells from the pancreatic lymph nodes of subjects with T1D respond to the first 15 amino acids of the insulin A-chain.
3904 19299644 Proinflammatory cytokines including tumor necrosis factor-alpha and interleukin-6 secreted by adipose tissue during the metabolic syndrome are proposed to cause local and general insulin resistance and promote development of type 2 diabetes.
3905 19299644 In spite of intense local inflammation, insulin sensitivity was not impaired in adipose tissue of Apoe(-/-)xCD4dnTGFbR mice unless exogenous interleukin-6 was administered.
3906 19324019 The thiazolidinedione rosiglitazone, an agonist ligand for the nuclear receptor PPAR-gamma, improves insulin sensitivity in part by stimulating transcription of the insulin-sensitizing adipokine adiponectin.
3907 19330314 We aimed to investigate the effect of a common WFS1 single-nucleotide polymorphism on several aspects of insulin secretion.
3908 19357831 Previous findings in rodents used as a model of diabetes suggest that insulin activation of atypical protein kinase C (aPKC) is impaired in muscle, but, unexpectedly, conserved in liver, despite impaired hepatic protein kinase B (PKB/Akt) activation.
3909 19357831 In liver, as well as in muscle, IRS-2/PI3K activation by insulin was intact, whereas IRS-1/PI3K activation by insulin was impaired.
3910 19357831 Moreover, hepatic IRS-2 is known to control hepatic aPKC during insulin activation.
3911 19365392 This is evident from the recent success of glucagon-like peptide 1 (GLP1) mimetics and dipeptidyl peptidase 4 (DPP4) inhibitors, which promote activation of the GLP1 receptor to stimulate insulin secretion and inhibit glucagon secretion, and also have the potential to increase beta-cell mass.
3912 19368716 Lower endotoxin and higher adiponectin in the groups treated with RSG may be related and indicate another mechanism for the effect of RSG on insulin sensitivity.
3913 19374858 Plasma cell membrane glycoprotein-1 or ectonucleotide pyrophosphatase/phosphodiesterase (PC-1/ENPP1) has been shown to inhibit insulin signaling, and its genetic polymorphism or increased expression is associated with type 2 diabetes in humans.
3914 19374858 Since patients with phosphodiesterase/pyrophosphatase deficient PC-1 manifest abnormal calcification, enhancing insulin signaling by inhibiting PC-1 for the treatment of diabetes will be feasible only if PC-1 phosphodiesterase/pyrophosphatase activity needs not be significantly diminished.
3915 19374858 In HEK293 cells stably expressing recombinant insulin receptor or insulin-like growth factor 1 (IGF1) receptor, transient expression of wild-type full length PC-1 (PC-1.FL.WT) but not the T256A or T256S mutants inhibits insulin signaling without affecting IGF1 signaling.
3916 19374858 Together, these results suggest that the inhibition of insulin signaling by PC-1 is somewhat specific and is dependent upon the enzymatic activity of the phosphodiesterase/pyrophosphatase.
3917 19375579 Plasma concentrations of GIP and GLP-1 were determined frequently during a 75-g glucose tolerance test, and insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp.
3918 19375596 Plasma Ang II is associated with body weight, decreases during weight loss, and is associated with markers of insulin resistance in obese subjects with T2D.
3919 19383476 Insulin is a 51-residue polypeptide hormone, with its two polypeptide chains linked by one intrachain and two interchain disulfide bonds, and has long been known to self-assemble in vitro into amyloid fibrils.
3920 19387119 Insulin influences Abeta production by modulating alpha-secretase activity and Abeta degradation.
3921 19388975 Hepatocyte nuclear factor-1 alpha (HNF1A) gene mutations are the commonest cause of monogenic diabetes, but patients are often misdiagnosed as having Type 1 diabetes and started on insulin treatment.
3922 19388975 We aimed to assess if patients do change from insulin to sulphonylurea treatment when HNF1A diabetes is confirmed and the impact of this treatment change on long-term glycaemic control.
3923 19390150 Inhibition of acetyl-CoA carboxylase (ACC) may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme an attractive pharmaceutical target.
3924 19390610 While this interaction constitutes an adaptive response that allows managing energy resources under stress conditions, excessive JNK activity in adipose tissue of vertebrates has been found to cause insulin resistance, promoting type II diabetes.
3925 19401434 We generated transgenic mice overexpressing the hGPR40 gene under control of the mouse insulin II promoter and used them to examine the role of GPR40 in the regulation of insulin secretion and glucose homeostasis.
3926 19401434 Normal (C57BL/6J) and diabetic (KK) mice overexpressing the hGPR40 gene under control of the insulin II promoter were generated, and their glucose metabolism and islet function were analyzed.
3927 19401434 In comparison with nontransgenic littermates, hGPR40 transgenic mice exhibited improved oral glucose tolerance with an increase in insulin secretion.
3928 19401434 Although islet morphologic analysis showed no obvious differences between hGPR40 transgenic and nontransgenic mice, isolated islets from hGPR40 transgenic mice had enhanced insulin secretion in response to high glucose (16 mmol/l) compared with those from nontransgenic mice, and they both had similar low glucose (3 mmol/l)-stimulated insulin secretion.
3929 19023195 We hypothesized that altered RBP levels in CKD could be one factor contributing to the uremic insulin resistance.
3930 19122346 Furthermore, it has been reported that over-expression of KLF11 has a deleterious effect on insulin promoter activity.
3931 19127383 In patients with moderate-to-severe obstructive sleep apnea, compliant CPAP usage may improve insulin secretion capacity, reduce leptin, total cholesterol, and low-density lipoprotein levels.
3932 19235132 In this study, we investigated the role of protein kinase B (Akt) and p42/44 mitogen-activated protein kinase (ERK 1/2) signaling pathways in mediating the mitogenic action of INS in VSMCs.
3933 19235132 Incubation of rat VSMCs with INS (100 nM) for 10 min resulted in an increase of Akt phosphorylation by 6-fold (p<0.001) and ERK 1/2 phosphorylation by 3-fold (p<0.001).
3934 19235132 Prolonged treatment of VSMCs with INS for 24 h did not have an effect on either Akt or ERK1/2 phosphorylation.
3935 19235132 These results indicate that INS acts through Akt and ERK 1/2 signaling pathways to up-regulate proliferation of VSMC's.
3936 19243309 JNK1 (c-Jun N-terminal kinase 1) plays a crucial role in the regulation of obesity-induced insulin resistance and is implicated in the pathology of Type 2 diabetes.
3937 19258404 We assessed whether the risk alleles in TCF7L2, CDKAL1, HHEX, SLC30A8, IGF2BP2, CDKN2A/2B, JAZF1, and WFS1 reduce insulin secretion in an additive manner and whether their impact is influenced by insulin sensitivity.
3938 19258404 In our cohort, only polymorphisms in SLC30A8, HHEX, TCF7L2, and CDKAL1 influenced insulin secretion.
3939 19264802 Our aim was to examine the role of Glis3 in beta cells, specifically with regard to regulation of insulin gene transcription.
3940 19264802 We demonstrate that insulin 2 (Ins2) mRNA expression in rat insulinoma 832/13 cells is markedly increased by wild-type Glis3 overexpression, but not by the NDH1 mutant.
3941 19264802 Glis3 also may indirectly affect insulin promoter activity through upregulation of MafA and downregulation of Nkx6-1.
3942 19264802 This study uncovers a role of Glis3 for regulation of insulin gene expression and expands our understanding of its role in the beta cell.
3943 19273608 Insulin stimulation of betaIRKO and betaIRS2KO cells led to blunted activation of phosphatidylinositol 3-kinase and Akt kinase, while surprisingly, glucose failed to activate either kinase but phosphorylated extracellular signal-regulated kinase.
3944 19276229 We sought to determine whether polymorphisms of the scavenger receptor class B, member I (SCARB1), an estrogen-regulated chromosome 12q24 positional candidate diabetes gene, were associated with type 2 diabetes or insulin resistance in a sex-specific fashion.
3945 19276229 We evaluated 34 haplotype-tagged single-nucleotide polymorphisms (SNPs) of SCARB1 for their association with type 2 diabetes and measures of insulin resistance in two populations: a clinic-based sample of 444 Mexican-American women from Proyecto SALSA and a community-based sample of 830 white women from the Rancho Bernardo Study.
3946 19289493 Insulin resistance in Akt2(-/-) mice was inhibited by haplodeficiency of Pten, suggesting that other Akt isoforms can compensate for Akt2 function.
3947 19319465 BCAA treatment significantly suppressed glucose- and insulin-induced in vitro angiogenesis in the presence of VEGF.
3948 19332449 Glucagon-like peptide-1 (GLP-1) is an incretin hormone that potentiates insulin secretion in a glucose-dependent manner.
3949 19332493 The increased insulin secretion may compensate for hepatic insulin resistance possibly mediated by elevated GIP secretion.
3950 19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
3951 19336408 Insulin-induced changes in mtDNA, mitochondrial mass, intracellular ATP content, and transcripts of mitochondrion-associated genes were prevented by blockade of Akt activation with the phosphatidylinositol 3-kinase inhibitor LY294002.
3952 19336408 Finally, insulin suppression of mtDNA, ATP production, and expression of mitochondrion-related genes was largely prevented by inhibition of cyclic nucleotide phosphodiesterase with isobutylmethylxanthine.
3953 19356820 Vaspin levels were positively correlated with BMI-SDS, triglycerides, fasting insulin and HOMA-IR and negatively correlated with adiponectin levels and FGIR.
3954 19375767 Compared with normal rats, untreated diabetic rats had a 30% and 61% increase in lipoprotein lipase protein expression and activity, which were decreased by insulin and gliclazide (P < .05).
3955 19375767 Fatty acid translocase protein was down-regulated by 45% in untreated diabetic rats, which was up-regulated by 31% and 26% with insulin and gliclazide, respectively (P < .05).
3956 19375767 Insulin failed to affect fatty acid transport protein 1 and fatty acid binding protein expressions.
3957 19375767 Moreover, compared with normal rats, untreated diabetic rats had higher expressions of sterol regulatory element-binding protein 1c, tumor necrosis factor alpha, and Tyr(705) phosphorylation of signal transducer and activator of transcription 3 levels, which all were down-regulated after insulin treatment.
3958 19383491 Finally, we demonstrate that PPARgamma participates in the insulin-induced IDE expression in neurons.
3959 19383895 PSA values were significantly reduced in men with insulin treatment (-39%; P = 0.006) and oral diabetic medication (-24%; P = 0.030), and in men with elevated (6.1-6.9%) and highly (> or =7%) elevated hemoglobin A1c values (-15%, P = 0.004 and -29%, P = 0.003, respectively).
3960 19416712 Insulin-stimulated activation of Akt and suppression of gluconeogenesis in hepatocytes are enhanced by APPL1 overexpression, but are attenuated by APPL1 knockdown.
3961 19418936 It potentiates the insulin secretory response (incretin effect) by enhancing the endogenous post-prandial response of GLP-1 (incretin enhancer) in a glucose-dependent manner.
3962 19419916 Recently discovered adipocyte-derived proteins (leptin and adiponectin) might contribute to the pathologic mechanism linking obesity and insulin resistance.
3963 19419916 Leptin and adiponectin were found to be independently associated with HOMA-IR and fasting insulin concentration, but in divergent directions, after adjusting for potential confounding factors.
3964 19419916 The results suggest that leptin and adiponectin may be involved in the pathophysiologic link between obesity and insulin resistance independently.
3965 19427492 Indeed, there is a mounting body of evidence that the resultant insulin resistance in cardiovascular tissue and kidneys contributes to the development of endothelial dysfunction, HTN, atherosclerosis, CKD, and CVD.77 RAAS-associated signaling by way of the AT1R and MR, triggers tissue activation of the NADPH oxidase enzymatic activation and increased production of ROS.
3966 19427492 Oxidative stress in cardiovascular tissue is derived from both NADPH oxidase and mitochondrial generation of ROS, and is central to the development of insulin resistance, endothelial dysfunction, HTN, and atherosclerosis.
3967 19429177 The obtained results suggest that the improvement of insulin sensitivity by agmatine is produced by two mechanisms, stimulation of adrenal gland to enhance beta-endorphin secretion and a direct activation of peripheral I2-imidazoline receptor in tissues, for the amelioration of insulin action.
3968 19429364 Specific ERK inhibitor PD98059 inhibited the increase of insulin secretion by Angelica hirsutiflora extract in HIT-T15 cells and isolated mouse islets.
3969 19429374 To investigate the insulin sensitizing activity and antidiabetic effects of the ethyl acetate fraction of AC (ACE).
3970 19433249 The role of ERbeta is still unknown, yet ERalpha plays an important role in the regulation of insulin biosynthesis, insulin secretion and beta-cell survival.
3971 19433262 Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1alpha and HNF-3beta activity.
3972 19442094 Enhanced insulin secretion as well as delayed gastric emptying, reduced glucagon secretion, and inhibited apoptosis of beta cells resulting from blockade of incretin degradation, have been proposed as the major actions of DPP-IV inhibitors as antidiabetic agents.
3973 19442172 Indeed, high-fat diet feeding triggers the development of obesity, inflammation, insulin resistance, type 2 diabetes and atherosclerosis by mechanisms dependent of the LPS and/or the fatty acids activation of the CD14/TLR4 receptor complex.
3974 19442860 Serum adiponectin, interleukin-6 (IL-6) levels and urine ACR were determined, HOMA-IR and Gutt's index were calculated to evaluate IR and insulin sensitivity, respectively.
3975 19448691 However, unexpectedly, in mammalian muscle, PGC-1alpha overexpression contributed to the development of diet-induced insulin resistance.
3976 19448691 In contrast, when PGC-1alpha was overexpressed modestly, within physiological limits, mitochondrial fatty acid oxidation was increased, GLUT4 expression was upregulated, and insulin-stimulated glucose transport was increased.
3977 19448691 These studies suggest that massive PGC-1alpha overexpression, but not physiologic PGC-1alpha overexpression, induces deleterious metabolic effects, and that exercise-induced improvements in insulin sensitivity are induced, in part, by the exercise-induced upregulation of PGC-1alpha.
3978 19448708 In skeletal muscle, both insulin and muscle contractions mediate translocation of glucose transporter GLUT4 to the plasma membrane proper, the sarcolemma, and the specialized membrane channel network, the transverse (t)-tubules.
3979 19448717 In this review, it is proposed that a pharmacologically imposed net internalization of CD36 and FABPpm is the preferable strategy to limit LCFA entry and accumulation of LCFA metabolites, to regress cardiac insulin resistance and, eventually, prevent diabetic heart failure.
3980 19449672 Fasting insulin and insulin resistance as assessed by QUICKI did not correlate with CRP, fitness, or fatness in these non-obese children.
3981 19449752 Thiazolidinediones, in particular of the rosiglitazone type, have a positive impact on increased tissue sensitivity to insulin built on the activation of PPAR-gamma.
3982 18672341 Liver glycogen metabolism plays an essential role in maintaining glucose homeostasis, we investigated the effect of resistin on liver glycogen metabolism and attempted to identify its role in initiating insulin resistance and type 2 diabetes.
3983 18672341 Hepatocytes exposed to resistin, but only in the presence of insulin, show a decrease in insulin-stimulated glycogen content.
3984 18672341 These results strongly suggest that resistin effects glycogen metabolism at the protein level, and resistin is highly associated with insulin resistance and type 2 diabetes and is a candidate for the prevention and treatment of type 2 diabetes.
3985 19213846 Cytochalasin D eliminated this difference and normalized insulin and glucagon secretion in NCAM(-/-) islets.
3986 19336678 At the end of the study, hyperinsulinemic-euglycemic clamps were performed and skeletal muscle (vastus lateralis) was obtained in the basal and insulin-stimulated states for insulin receptor signaling and gene expression profiling.
3987 19371350 After 3-4 weeks of treatment, combination treatment increased plasma insulin by 3.8-fold, decreased plasma glucagon by 41%, both of which were greater than each drug alone, and increased plasma adiponectin by 2.4-fold.
3988 19371350 Combination treatment also increased expression of insulin and pancreatic and duodenal homeobox 1 (PDX1), maintained normal beta-cell/alpha-cell distribution in islets and restored pancreatic insulin content to levels comparable to non-diabetic mice.
3989 19380455 Baseline OPG correlated with fasting insulin, baseline lactate, and low density lipoprotein cholesterol in the diabetic group, and with baseline FFA in the lean group.
3990 19389808 MBX-102 exhibits full therapeutic activity without the classical PPAR-gamma side effects and may represent the next generation insulin sensitizer.
3991 19389813 Adiponectin has been postulated to affect lipid and insulin signal transduction pathways.
3992 19389813 In multivariable linear regression models that included sex, BMI, waist circumference, homeostasis model assessment of insulin resistance, and leptin, adiponectin was associated with mean LDL size (standardized regression coefficient B = 0.20; P < 0.001), VLDL size (B = -0.12; P < 0.001), and HDL size (B = 0.06; P = 0.013).
3993 19389813 Adiponectin is favorably associated with lipoprotein particle size and subclass distribution independent of adiposity and insulin sensitivity.
3994 19389827 The pharmacological suppression of this insulin-stimulated ROS elevation, either by antioxidant or by an NADPH oxidase inhibitor, abolished the anorexigenic effect of insulin.
3995 19394382 The adipocyte-derived hormone, leptin controls feeding behavior, augments fatty acid beta-oxidation in the skeletal muscle, attenuates insulin secretion but enhances whole body insulin sensitivity and glucose disposal, thereby serving as a promising therapeutic candidate for the treatment of insulin resistance and dyslipidemia.
3996 19401420 In addition to its central action, leptin directly affects pancreatic beta-cells, inhibiting insulin secretion, and, thus, modulating glucose homeostasis.
3997 19467247 The present data demonstrates that the impaired PRMT1 activity may be implicated in glucose intolerance in GK rats through the disturbed hepatic glucose metabolism and insulin secretion.
3998 19533653 Therefore, the aim of this study was to determine whether there was an increase in catabolic signaling targets, such as atrogin-1, muscle ring finger-1 (MuRF1), forkhead transcription factor (FoXO), and myostatin, and decreases in anabolic signaling targets, such as insulin-like growth factor (IGF), v-akt murine thymoma viral oncogene (Akt), glycogen synthase kinase-beta (GSK-3beta), mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and p70(s6kinase) in chronic complete SCI patients.
3999 19534294 It has been suggested that insulin has an effect on nerve regeneration similar to that of nerve growth factor (NGF).
4000 19538235 To compare the effect of continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) on albumin excretion rate (AER) in Type 1 diabetic patients.
4001 19552838 Serum Chemerin is correlated with insulin level, body fat disposition and lipid metabolism which suggesting that it may play a role in the pathophysiology of obesity and metabolic syndrome.
4002 19552844 The insulin level, HOMA-IR, and BMI were negatively correlated with LPL (r = -0.232 - 0.297, P < 0.05).
4003 19555519 The mechanisms proposed which may underlie this effect include potential relationships with improvements in lean mass, regulation of insulin release, altered insulin receptor expression and specific effects on insulin action.
4004 19076162 Fosinopril significantly reduced the degree of hepatic steatosis, serum FG, insulin, ALT, TNF-alpha and IL-6 concentrations and hepatic TNF-alpha and IL-6 mRNA expression.
4005 19076162 In conclusion, the ACEI improved insulin sensitivity and hepatic steatosis in rats with T2DM by increasing circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro-inflammatory cytokine levels in the circulation and liver.
4006 18839335 Resistin, an adipokine-linked obesity with type 2 diabetes, impairs glucose-stimulated insulin secretion (GSIS) in beta-cells.
4007 19367376 Herein, we examined the effects of chronic exposure of insulin-secreting beta-(INS 832/13) cells to high glucose (a model for glucotoxicity), palmitate (a model for lipotoxicity), or glucose plus palmitate (a model for glucolipotoxicity) on the expression and activity of nm23-H1 (NDP kinase A) and nm23-H2 (NDP kinase B).
4008 19440953 Both insulin and phloridzin could reverse the attenuation effects of hyperglycemia on BMP-7 and BMP-RII expressions in the kidneys of streptozotocin-induced diabetic rats through the correction of hyperglycemia.
4009 19470629 The objective of the study was to compare responses of plasma levels of IGF-I and IGF binding proteins (IGFBP-1 and IGFBP-3) induced by human regular insulin (HI) and the long-acting insulin analog detemir (IDet) at doses equivalent with respect to the glucose-lowering effect.
4010 19470629 Insulin infusion resulted in a suppression of plasma IGFBP-1 concentrations with no differences between IDet (baseline, 16.6 +/- 3.8 ng/ml; endpoint, 2.0 +/- 0.6 ng/ml) and HI (baseline, 16.6 +/- 4.1 ng/ml; endpoint, 2.6 +/- 1.4 ng/ml) (P > 0.2) and study conditions (P > 0.2).
4011 19497592 Serum ET-1 level averaged 1.09 (0.48) pg/mL and correlated positively with glucose handling-associated parameters (insulin, r = 0.22; HOMA, r = 0.21; HbA(1c), r = 0.23; all Ps < .05) and negatively with constituents of antioxidative protection system (FRAP, r = -0.45; SOD, r = -0.47; both Ps < .0001; vitamin C, r = -0.27; P < or = .01).
4012 19501121 The percentage of cells expressing Pdx-1 alone or together with INGAP or insulin increased significantly in ducts.
4013 19506561 Adipocyte diameter (by microscope technique; n=29), expression of candidate genes (by quantitative real-time PCR) in freshly isolated adipocytes (monocyte chemoattractant protein (MCP) 1 and MCP2, macrophage inflammatory protein (MIP) 1alpha, MIP1beta and MIP2, macrophage migration inhibitory factor (MIF), tumor necrosis factor alpha, interleukin (IL) 6 and IL8; n=22) and cultured preadipocytes (MCP1, MIP1alpha, MIF, IL6 and matrix metalloproteinase 2; n=33) from subcutaneous abdominal adipose tissue (by aspiration biopsy, n=34), body fat by dual-energy X-ray absorptiometry, glucose tolerance by 75 g oral glucose tolerance test and insulin action by euglycemic-hyperinsulinemic clamp (insulin infusion rate 40 mU m(-2) min(-1)) (all n=34).
4014 19506561 MIF was the only gene whose expression in both freshly isolated adipocytes and cultured preadipocytes was positively associated with adipocytes diameter and negatively associated with peripheral and hepatic insulin action (all P<0.05).
4015 19509109 During 1 yr of insulin therapy, mean body weight increased by 6%, whereas the fasting leptin levels increased by 108% (both P < 0.001).
4016 19509109 Study 2: mean body weight increased by 4% (P < 0.01), whereas leptin levels increased by 56% (P < 0.001) during 1 yr of insulin treatment and the increase in leptin preceded the increase in body weight.
4017 19509109 Significant correlations were observed between insulin's effect on serum leptin levels and the increase in weight that accompanied insulin therapy.
4018 19531641 This correlated with the ability of rosiglitazone to enhance insulin sensitivity for stimulation of protein kinase B (Akt) phosphorylation and glucose transport; rosiglitazone also corrected high-glucose-induced insulin resistance in L6 cells.
4019 19531641 Induction of obesity and insulin resistance in rats by feeding a high-fat high-sucrose diet also led to decreased muscle HMW adiponectin content that could be corrected by rosiglitazone treatment.
4020 19576197 Thus, in mice, MafA expression in Pdx1+ pancreatic progenitors is not sufficient to specify insulin+ cells but in fact deters pancreatic development and the differentiation of endocrine cells.
4021 19596470 Tolbutamide-induced insulin secretion was also suppressed in the AP-2beta-overexpressing cells, but KCl-induced insulin secretion was not affected by AP-2beta overexpression.
4022 19596470 We identified for the first time that AP-2beta expressed and functioned in insulin-secreting cell-line HIT-T15.
4023 19602578 The present study was undertaken to characterize the effect of IDS overexpression on insulin release.
4024 19602578 INS1E cells were transiently transfected with a construct encoding human IDS (hIDS). hIDS overexpression was associated with a gain of function detected by a reduction in heparan sulfate content. hIDS potentiated the glucose-stimulated insulin secretory response compared with controls (61%) with no changes in insulin mRNA levels or insulin peptide content.
4025 19604125 Macrophage-derived IL-1beta production in insulin-sensitive organs, leads to progression of inflammation and induction of insulin resistance in obesity.
4026 19655390 In pancreatic islets, insulin production is linked with zinc transport mediated by zinc transporter ZnT-8, a product of the SLC30A8 gene.
4027 19655390 Therefore, altered activity of ZnT-8 is expected to be associated with impaired glucose-induced insulin response and promote progression from glucose intolerance to diabetes.
4028 19656489 Islet transduction with dominant-negative Pdx1 (RIPDN79PDX1) impairs mitochondrial metabolism and glucose-stimulated insulin secretion (GSIS).
4029 19679549 Insulin enhanced GPCR signaling through a rapamycin-sensitive mTOR-dependent pathway.
4030 19679549 Metformin pretreatment completely abrogated insulin-induced potentiation of Ca(2+) signaling but did not interfere with the effect of GPCR agonists alone.
4031 19679549 Insulin also enhanced GPCR agonist-induced growth, measured by DNA synthesis, and the number of cells cultured in adherent or nonadherent conditions.
4032 19111928 Lipid induced NF-kappaB activation is known to be associated with insulin resistance and type2 diabetes.
4033 19111928 Overexpression of NF-kappaB p65 by palmitate was linked to impairment of insulin activity.
4034 19501859 Alterations of this interaction have been suggested to be implicated in the elevation of RBP4 that are thought to contribute to the development of insulin resistance associated with obesity and type 2 diabetes mellitus (T2DM).
4035 19558269 Peroxisome proliferator-activated receptor gamma2 (PPARgamma2) is a nuclear receptor that regulates adipocyte differentiation, lipid metabolism, and insulin sensitivity.
4036 19581416 We identified tissue inhibitor of metalloproteinase 3 (TIMP3), the endogenous inhibitor of A disintegrin and metalloprotease domain 17 (ADAM17) and other matrix metalloproteinases (MMPs), as a gene modifier for insulin resistance and vascular inflammation in mice.
4037 19581418 The IRS-1 protein expression was reduced and the serine phosphorylation of PKB in response to insulin attenuated whereas basal and insulin-stimulated phosphorylation of extracellular signal-related kinase (ERK)1/2 was increased in type 2 diabetes MVEC.
4038 19584308 Here we studied whether a common variant in KCNQ1 would influence BMI as well as insulin secretion and action and predict future type 2 diabetes in subjects from Sweden and Finland.
4039 19591659 Incretins such as glucagon-like peptide-1 (GLP-1) are gut-derived hormones that stimulate insulin secretion and suppress glucagon secretion, thus playing a key role in glucose homeostasis.
4040 19591659 Small exploratory studies suggest that GLP-1 safely reduces hyperglycemia without causing hypoglycemia, a key advantage over insulin if efficacy is established in larger studies.
4041 19592617 Naringenin 1) increased hepatic fatty acid oxidation through a peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha/PPARalpha-mediated transcription program; 2) prevented sterol regulatory element-binding protein 1c-mediated lipogenesis in both liver and muscle by reducing fasting hyperinsulinemia; 3) decreased hepatic cholesterol and cholesterol ester synthesis; 4) reduced both VLDL-derived and endogenously synthesized fatty acids, preventing muscle triglyceride accumulation; and 5) improved overall insulin sensitivity and glucose tolerance.
4042 19602536 Patients that did not become insulin independent exhibited significantly higher counts of B-cells as well as a T-cell autoreactivity against insulinoma-associated protein 2 (IA2) and/or GAD.
4043 19608644 Here we demonstrate that overexpression of Forkhead-related transcription factor (Fox)O1, FoxO3a, and FoxC1 augment insulin's ability to activate the PAI-1 promoter.
4044 19608653 IGF-I increased NO synthase activity to an extent similar to that seen with insulin and in-vivo IGF-I led to serine phosphorylation of endothelial NO synthase (eNOS).
4045 19625203 The aim of the present study was to assess the effect of FTO variation on obesity, insulin sensitivity, and metabolic and hormonal profiles in PCOS.
4046 19627255 There is concern, however, that the increase in glucose oxidation caused by less inhibition of the pyruvate dehydrogenase complex by phosphorylation will inhibit fatty acid oxidation, promote ectopic fat accumulation and worsen insulin sensitivity.
4047 19628478 We demonstrate that mutant huntingtin impairs glucose-stimulated insulin secretion in insulin-producing beta-cells, without altering stored levels of insulin.
4048 19628574 The comparative analysis of beta-cells from wild-type and LDL receptor-deficient mice revealed that the inhibitory effect of LDL on insulin secretion but not proliferation requires the LDL receptor.
4049 19628651 To investigate the effects of unacylated ghrelin (UAG) and co-administration of acylated ghrelin (AG) and UAG in morbid obesity, a condition characterized by insulin resistance and low GH levels.
4050 19629054 Our data suggest that change in the large adipocyte subfraction may contribute to the improvement in insulin sensitivity via an increase in serum adiponectin.
4051 19647467 We examined whether parenteral regular insulin can prevent diabetes in IA-2 antibody-positive (IA-2A+) relatives of type 1 diabetic patients, using a trial protocol that differed substantially from that of the Diabetes Prevention Trial-1.
4052 19685554 In the whole cohort and in women, univariate correlations between IL-6 concentrations and the parameters under evaluation showed that IL-6 and leptin were positively correlated with age, BMI, waist, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, fasting insulin, Delta AUC insulin area, triglyceride (TG), free fatty acids (FFA) and monocyte chemoattractant protein-1 (MCP-1) and inversely correlated with HDL cholesterol (HDL-C) and adiponectin.
4053 19685554 In women a forward stepwise linear regression analysis in a model including age, BMI, features of metabolic syndrome, fasting insulin, Delta AUC insulin and insulin sensitivity index (ISI) index revealed that only IL-6 and leptin were independently associated with fasting insulin levels.
4054 19689798 Transcription factors PPARgamma, NFAT5, CREB5 and EBF1, the adipokine NAMPT, members of the insulin signaling cascade SORBS1 and IGF1 and IL6ST were repressed, while the adipokine THBS1 and GLUT4 involved in insulin signaling were induced.
4055 19690174 Human and rat primary beta cells were sorted by FACS and cultured for 24 h +/- 20 ng/ml TNF-alpha to explore the impact on apoptosis, proliferation, and short-term insulin secretion (1 h, 2.8 mm glucose followed by 1 h, 16.7 mm glucose at the end of the 24-h culture period) as well as key signaling protein phosphorylation and expression.
4056 19698699 TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-gamma) and improve systemic insulin sensitivity.
4057 19698699 Down-regulation of LPL message and protein levels using siRNA resulted in a similar increase in insulin-dependent glucose uptake.
4058 19699714 In addition, we found that this effect of Rg3 on insulin signaling was not mediated by the AMPK pathway.
4059 19699714 In conclusion, these results suggest that Rg3 improves insulin signaling and glucose uptake primarily by stimulating the expression of IRS-1 and GLUT4.
4060 19716806 In conclusion, glucose-mediated inhibition of cholesterol biosynthesis perturbs lipid raft stability, resulting in a loss of syntaxin 1A from granule docking sites and inhibition of insulin secretion.
4061 19734900 Unlike previously reported T2D risk loci, which predominantly associate with impaired beta cell function, the C allele of rs2943641 was associated with insulin resistance and hyperinsulinemia in 14,358 French, Danish and Finnish participants from population-based cohorts; this allele was also associated with reduced basal levels of IRS1 protein and decreased insulin induction of IRS1-associated phosphatidylinositol-3-OH kinase activity in human skeletal muscle biopsies.
4062 19766907 The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPARgamma) has been associated with decreased obesity, insulin resistance, type 2 diabetes and other age-associated diseases such as cognitive impairment, hypertension, cancer, osteoarthritis.
4063 19767827 Glucagon-like peptide-1 (GLP-1) ameliorates the symptoms of diabetes through stimulation of insulin secretion.
4064 19767827 With exendin-4 treatment on diabetic mice, the following results were noted: (i) exendin-4 suppressed the increase in plasma glucose and inhibited somatostatin expression induced by STZ, (ii) reduction of insulin prevalence was inhibited, while expression of p75 neurotrophin receptor (p75NTR), pancreatic nerve growth factor (NGF), and NGF-positive islet cell prevalence increased, (iii) there were no alterations in the severity of proliferated cell nuclear antigen positive or apoptotic beta cells in pancreatic islets, and (iv) pancreatic catalase, glutathione peroxidase, and superoxide dismutase activities significantly increased.
4065 19769745 As the transcription factor Foxa2 has been implicated, in part, in the regulation of gluconeogenic genes, we studied the effects of TNFalpha and/or insulin on its cellular status in hepatocytes, followed by an assessment of its occupancy on the phosphoenolpyruvate carboxykinase (PEPCK) promoter.
4066 19769745 Preincubation of cells with TNFalpha, followed by insulin, significantly prevented insulin-mediated nuclear exclusion of Foxa2 and substantially increased its nuclear concentration.
4067 19769745 Insulin inhibition of PEPCK expression and the preventive effect of TNFalpha could be partially but significantly restored in the presence of Foxa2 siRNA.
4068 19769745 Our results indicate that another transcription factor, Foxa2, is at least partly responsible for the attenuating effect of TNFalpha on insulin action on PEPCK expression and glucose production in HepG2 cells.
4069 19775518 Exendin-4 treatment and transduction of PDX-1 and NeuroD proteins by protein transduction technology in HN#13 cells induced insulin and pancreas-related gene expression.
4070 19785303 The research question was, "How do youths' hemoglobin A(1c) (HbA(1c)) values change with insulin pump therapy?"
4071 19788607 Adiponectin knockout (KO) mice have been reported to cause insulin resistance and neointimal formation of the artery.
4072 19789144 The GRB10 protein binds to insulin and insulin-like growth factor receptors and acts as a negative regulatory protein.
4073 19789630 Assuming an additive genetic model the diabetes-associated major C-allele of rs4607103 near ADAMTS9 associated with reduced insulin-stimulated glucose uptake (p = 0.002) during a hyperinsulinemic euglycemic clamp.
4074 19789630 The present studies suggest that the diabetogenic impact of the C-allele of rs4607103 near ADAMTS9 may in part be mediated through decreased insulin sensitivity of peripheral tissues.
4075 19791828 This increases GLP-1 levels, stimulates insulin secretion and reduces postprandial glucagon and glucose levels.
4076 19602560 This study aimed to explore the role of the PAT proteins OXPAT and ADRP in skeletal muscle lipid metabolism and their putative role in modulating insulin sensitivity.
4077 19615701 Castration elevated the blood glucose level, which was accompanied by inhibitory effect on serum insulin, Akt phosphorylation, GLUT4 expression and its plasma membrane population, glucose uptake, glycogen and glycogen synthase activity, and stimulatory effect on GLUT2 expression and glycogen phosphorylase activity in tissues studied.
4078 19622614 The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion also reduce birth weight, and an association of low birth weight and the type 2 diabetes risk alleles at the HHEX-IDE and CDKAL1 loci were recently reported.
4079 19622628 We conclude that variation in ACP1 is associated with fasting insulin and insulin sensitivity in a sex-specific manner.
4080 19663918 The urinary MCP-1/Cr and urinary ICAM-1/Cr ratios in type 2 diabetic patients with microalbuminuria were much higher than those in normal controls, and intensive insulin treatment could decrease significantly the urinary MCP-1/Cr, ICAM-1/Cr and Alb/Cr ratios in type 2 diabetics with microalbuminuria.
4081 19663918 Intensive insulin treatment may protect against renal injury in early DN by reducing the urinary MCP-1 and ICAM-1 excretions.
4082 19671707 Multiple stepwise regression analysis showed that age, %fat, high-density lipoprotein cholesterol, fasting plasma glucose, and fasting serum insulin were independently associated with osteocalcin in men (P<0.05).
4083 19674864 Concurrent decreases in TNF-alpha and adipose tissue mass suggest that in dogs, as in humans, this adipokine may be implicated in the insulin resistance of obesity.
4084 19688337 We investigated whether reduced levels of muscle AMPK promote lipid accumulation and insulin resistance during high-fat feeding.
4085 19694723 The lipid phosphatase known as SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) plays an important role in the regulation of the intracellular insulin signalling pathway.
4086 19733151 Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration.
4087 19735958 An association between serum syndecan-1 and intake of exogenous insulin was found (r=0.266, p=0.035).
4088 19735958 Chronic inflammation and exogenous insulin usage increases serum syndecan-1 level.
4089 19766107 The dipeptidyl peptidase (DPP)-IV inhibitor ASP8497, (2S,4S)-4-fluoro-1-({[4-methyl-1-(methylsulfonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile monofumarate, inhibits the degradation of glucagon-like peptide-1 (GLP-1), an incretin hormone, and promotes insulin secretion in a glucose-dependent manner.
4090 19799857 Insulin therapy increased both PAP(1) activity and lipin mRNA expression in diabetic patients.
4091 19806227 Sirt-1 down-regulates p53 activity, rising lifespan, and cell survival; it also deacetylases peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its coactivator 1 alpha (PGC-1alpha), promoting lipid mobilization, positively regulating insulin secretion, and increasing mitochondrial dimension and number.
4092 19808019 In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs).
4093 19808019 The increased insulin sensitivity in Gpx1(-/-) mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the antioxidant N-acetylcysteine.
4094 19808019 Increased insulin signaling correlated with enhanced oxidation of the PTP family member PTEN, which terminates signals generated by phosphatidylinositol-3-kinase.
4095 19808023 ClC-3 expression in the insulin granule was demonstrated by immunoblotting, immunostaining, and negative immuno-EM in a high-purification fraction of large dense-core vesicles (LDCVs) obtained by phogrin-EGFP labeling.
4096 19818293 The purpose of this study was to assess monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) levels and their association with insulin resistance and adiponectin concentrations in CAD patients, who were categorized as having T2DM, MS, or neither.
4097 19826189 The purpose of the present study was to investigate the involvement of cyclooxygenase-2 (COX-2) and prostaglandin E(2) in the effects of insulin on gastric emptying in male rats.
4098 19826189 The COX inhibitor, indomethacin, decreased the gastric emptying which was induced or reversed by insulin in normal and DM rats, respectively.
4099 19282820 HFCS-55 induced a downregulation of the insulin signaling pathway, as indicated by attenuated (ser473)phosphorylation of AKT1.
4100 19474523 In this study, we used two cellular models of insulin resistance, one induced by treatment with tumor necrosis factor-alpha (TNF-alpha) and the other with the glucocorticoid dexamethasone.
4101 19474523 Gene expression analysis showed that SAA3 mRNA levels were increased in both models of insulin resistance, and ELISA showed that A-SAA levels were increased in both models too.
4102 19506327 This improved glycemic control, reduced daily insulin requirement, decreased IL-6 and hs-CRP levels rapidly and increased adiponectin level at 10 days after initiation of therapy.
4103 19536736 We found significant independent effects of the PPARG and PPARGC1A variants on fasting insulin levels (p=0.02 for both), HOMA-IR (p=0.03 and p=0.02, respectively), insulin area under the curve (AUC) (p=0.007 and p=0.006, respectively) and 2-h glucose levels (p=0.02 for PPARGC1A).
4104 19536736 Together, these results showed that PPARG Pro12Ala and PPARGC1A Gly482Ser variants are associated, alone and in interaction, with insulin and glucose homeostasis and suggest that gene-gene interactions should be taken into account in candidate gene studies of T2DM to identify subjects with markedly different risks of developing the disease.
4105 19622624 A down-regulation of ZAG in SAT, VAT, and liver exists in obese patients but seems unrelated to insulin resistance.
4106 19651814 In a genome-wide association scan, the rs738409 C>G single nucleotide polymorphism (SNP) in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with increased liver fat but not with insulin resistance estimated from fasting values.
4107 19651815 Although TNKS deficiency does not compromise insulin-stimulated GLUT4 translocation in primary adipocytes, it leads to the post-transcriptional upregulation of GLUT4 and adiponectin in adipocytes and increases plasma adiponectin levels.
4108 19651815 TNKS-deficient mice exhibit increases in energy expenditure, fatty acid oxidation, and insulin-stimulated glucose utilization.
4109 19660440 GPR40 is the best characterised of this group and appears to mediate the acute stimulatory effects of long chain fatty acids on insulin secretion.
4110 19675134 Inhibiting nitric oxide synthase blocks insulin's but not contraction's effects.
4111 19675134 The paradoxical MBV decline seen with insulin plus FFA may result from differential inhibition of insulin-stimulated nitric oxide-dependent vasodilation relative to ET-1 vasoconstriction.
4112 19675136 Transgenic expression of diacylglycerol acyltransferase-1 (DGAT1) in skeletal muscle leads to protection against fat-induced insulin resistance despite accumulation of intramuscular triglyceride, a phenomenon similar to what is known as the "athlete paradox."
4113 19675137 The obELV-mediated induction of TNF-alpha and IL-6 in macrophages and insulin resistance requires the TLR4/TRIF pathway.
4114 19675138 Prereceptor facilitation of glucocorticoid action via 11beta-HSD1 increases pSer(307) IRS1 and may be crucial in mediating insulin resistance in skeletal muscle.
4115 19690064 These results demonstrate that IL-10 increases insulin sensitivity and protects skeletal muscle from obesity-associated macrophage infiltration, increases in inflammatory cytokines, and their deleterious effects on insulin signaling and glucose metabolism.
4116 19698772 In intraperitoneal glucose tolerance testing in rats, marked improvement of hypoglycemic effects were observed in anionic liposomal formulation of GLP-1 (100 nmol/kg) with 1.7-fold higher increase of insulin secretion, as compared to GLP-1 solution.
4117 19717727 The insulin-induced relaxation was inhibited by treatment with an Akt inhibitor in control and diabetic aortas, but not in the HI-diabetic aorta.
4118 19717727 These results suggest that the plasma insulin level has a close relation to the level of aortic PDK-1/Akt (at Thr(308))/NOS activities, and that reduced actions of the PDK-1/Akt (at Thr(308)) signal pathway may contribute to the impairments of insulin-induced endothelial functions seen in hyperinsulinemic diabetes.
4119 19720802 This study was aimed to ascertain whether GPR40 controls insulin secretion in vivo and modulates intracellular fuel metabolism in islets.
4120 19731235 We have shown that the iminosugar N-(5'-adamantane-1'-yl-methoxy)-pentyl-1-deoxynojirimycin (AMP-DNM), an inhibitor of the enzyme glucosylceramide synthase, is a potent enhancer of insulin signaling in rodent models for insulin resistance and type 2 diabetes.
4121 19740738 Insulin stimulates the translocation of the glucose transporter GLUT4 from intracellular locations to the plasma membrane in adipose and muscle cells.
4122 19740738 However, the regulation of a very similar protein, TBC1D1 (TBC domain family, member 1), which is mainly found in muscle, in insulin-stimulated GLUT4 translocation has been unclear.
4123 19740738 We show that a mutant of TBC1D1, in which several Akt sites have been converted to alanine, is considerably more inhibitory to insulin-stimulated GLUT4 translocation than wild-type TBC1D1.
4124 19741193 No differences in insulin or PDGF-induced phosphorylation of ERK-1/2 or components of the Akt pathway (Akt-Ser473, Akt-Thr308, and GSK-3beta) were apparent between the two populations.
4125 19764891 SGK1 is activated by insulin and growth factors via PI3K, 3-phosphoinositide dependent kinase PDK1 and mTOR.
4126 19776253 To link insulin resistance, aging, and cardiovascular disease, we examined the expression and glycosylation pattern of PAI-1 in liver and white adipose tissue (WAT) from adult (3 mo) and insulin-resistant old (24 mo) Wistar rats.
4127 19789205 Adiposity and insulin resistance explained most of the association of bioavailable T but only partially explained the associations of E2 and SHBG with incident T2DM among postmenopausal women.
4128 19790256 Given its central role in the regulation of insulin release it is understandable that mutations in the gene encoding glucokinase (GCK) can cause both hyper- and hypoglycemia.
4129 19802467 Neuronal apoptosis occurs in the diabetic brain due to insulin deficiency or insulin resistance, both of which reduce the expression of stem cell factor (SCF).
4130 19802467 SCF expression was lower in the diabetic cortex than in the normal cortex; however, insulin increased the expression of SCF in the diabetic cortex.
4131 19819977 Expression of the orphan nuclear receptor Nur77, which is induced by beta-adrenergic signaling and is associated with insulin sensitivity, was lower in LCR (P < 0.05).
4132 19852718 This capacity can be modulated by SGLT2 inhibitors thereby providing a unique insulin independent method of treatment of diabetes.
4133 19858063 We consider monotherapy, dual therapy, and triple therapy, including 8 major classes of medications (biguanides, dipeptidyl-peptidase-4 inhibitors, incretin mimetics, thiazolidinediones, alpha-glucosidase inhibitors, sulfonylureas, meglitinides, and bile acid sequestrants) and insulin therapy (basal, premixed, and multiple daily injections), with or without orally administered medications.
4134 19859528 While serotonin (5-HT) co-localization with insulin in granules of pancreatic beta-cells was demonstrated more than three decades ago, its physiological role in the etiology of diabetes is still unclear.
4135 19859528 We combined biochemical and electrophysiological analyses of mice selectively deficient in peripheral tryptophan hydroxylase (Tph1-/-) and 5-HT to show that intracellular 5-HT regulates insulin secretion.
4136 19859528 Our results demonstrate that 5-HT regulates insulin secretion by serotonylation of GTPases within pancreatic beta-cells and suggest that intracellular 5-HT functions in various microenvironments via this mechanism in concert with the known receptor-mediated signaling.
4137 19877133 Moreover, the uncarboxylated form of osteocalcin was found to be associated with enhanced beta-cell function, and the carboxylated form was associated with improved insulin sensitivity in middle-aged male subjects.
4138 19881255 Diabetes reduced the amount of sEH protein in the liver and insulin restored the level of protein.
4139 19883613 PI3K signaling is thought to mediate leptin and insulin action in hypothalamic pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, through largely unknown mechanisms.
4140 19883616 We found that adding a small amount of glucose to the medium (2%) shortened the life span of C. elegans by inhibiting the activities of life span-extending transcription factors that are also inhibited by insulin signaling: the FOXO family member DAF-16 and the heat shock factor HSF-1.
4141 19114874 The implementation of a regular, rigorous exercise and diet program greatly decreased insulin resistance and allowed far more patients to reach their glycosylated hemoglobin goals.
4142 19623578 In conclusion, TCDD exposure impaired the second phase of glucose-stimulated secretion of insulin from the islets via the AhR signaling pathway.
4143 19657071 Akt phosphorylation in response to insulin was reduced in adipose and skeletal muscle of adult rats following exposure to LP diet in early life when compared to control-fed animals, but this was only apparent in males.
4144 19671994 Retinol-binding protein 4 (RBP4) is a newly discovered adipokine, which is reported to be correlated with insulin resistance (IR) and type 2 diabetes (T2DM).
4145 19672057 We recently demonstrated that adipocyte amyloid precursor protein (APP) expression is upregulated in obesity and correlates with insulin resistance and adipose tissue inflammation.
4146 19672057 At baseline, adipocyte APP expression correlated significantly with plasma Abeta40 levels and with 2-hour insulin concentrations.
4147 19672057 Changes in adipocyte APP expression correlated with changes in plasma Abeta40 levels (R = 0.74, p = 0.01) and changes in 2-hour insulin (R = 0.75, p = 0.01).
4148 19683471 Kinases, including IKKbeta, JNK, ERK, mTOR, and S6K, activated by the inducers of insulin resistance induce uncontrolled IRS serine phosphorylation.
4149 19696185 We investigated, herein, in vivo efficacy and associated molecular mechanisms by which PD153035, an EGFR tyrosine kinase inhibitor, improved diabetes control and insulin action.
4150 19696185 After 14 days of drug administration, there was a marked improvement in glucose tolerance; a reduction in insulin resistance; a reduction in macrophage infiltration in adipose tissue and in TNF-alpha, IL-6, and free fatty acids; accompanied by an improvement in insulin signaling in liver, muscle, and adipose tissue; and also a decrease in insulin receptor substrate-1 Ser(307) phosphorylation in JNK and inhibitor of NF-kappaB kinase (IKKbeta) activation in these tissues.
4151 19706988 Interestingly, insulin I and II, anti-apoptotic bcl-2, and proliferation promoting ERK-1 gene expressions were significantly upregulated in db/m mice.
4152 19706988 Expressions of insulin I and II, bcl-2, and ERK-1 gene were increased in db/m mice, but not in m/m fed a high fat diet.
4153 19720793 K(ATP) channel trafficking is regulated by energy status via AMPK, and this mechanism may play a key role in inhibiting insulin secretion under low energy status.
4154 19720798 Furthermore, higher chemerin release is associated with insulin resistance at the level of lipogenesis and insulin-induced antilipolysis in adipocytes.
4155 19720803 Fibroblast growth factor-21 (FGF-21) is a potent metabolic regulator, which in animal models has been shown to improve glucose metabolism and insulin sensitivity.
4156 19720803 Recently, FGF-21 was shown to be expressed and secreted from murine muscle cells in response to insulin stimulation.
4157 19720803 Furthermore, we investigated systemic levels and muscle FGF-21 expression in humans with or without insulin resistance and chronic elevated insulin.
4158 19720803 After 3 or 4 h of insulin infusion during a hyperinsulinemic-euglycemic clamp, muscular FGF-21 expression increased significantly.
4159 19720803 In individuals with chronic elevated insulin, muscular FGF-21 expression was associated with hyperinsulinemia in men but not in women.
4160 19741162 Loss of Nur77 expression in skeletal muscle impaired insulin signaling and markedly reduced GLUT4 protein expression.
4161 19741163 Glucokinase (GCK) and glucose-6-phosphatase catalytic subunit 2 (G6PC2) regulate the glucose-cycling step in pancreatic beta-cells and may regulate insulin secretion.
4162 19741163 Our data suggest that variation in GCK and G6PC2 have additive effects on both fasting glucose and insulin secretion.
4163 19752200 We conclude that PPARgamma activity is important for maintaining basal and insulin-dependent transepithelial Na+ transport and ENaC activity.
4164 19755407 We explored potential associations of two single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ; +45T>G, rs2241766 and +276G>T, rs1501299) with circulating total and high-molecular weight (HMW) adiponectin, insulin resistance (IR), and markers of obesity in a healthy Greek female population.
4165 19755407 The observed differences in HOMA-IR were very significant among women with a higher body fat (BF) percentage (>or= the population median of 41%; all P
4166 19755625 The novel changes described after the HFHC meal elucidate further the mechanisms underlying postprandial inflammation and also provide the first evidence explaining the pathogenesis of insulin and leptin resistance mediated by SOCS-3 after such meals.
4167 19765654 In conclusion, triple oral hypoglycemic therapy improves glycemic control, insulin sensitivity, retards diabetic cardiomyopathy and does not increased body weight; decrease more detrimental inflammatory markers, increase interleukin-10 and adiponectin in neonatal streptozotocin-induced IRtype2DM Wistar Albino Rats.
4168 19805515 In addition, we provide evidence that Glis3 regulates insulin gene expression through two Glis-binding sites in its proximal promoter, indicating that Glis3 also regulates beta-cell function.
4169 19819942 However, these effects on adiponectin do not translate into changes in metabolism or whole-body insulin sensitivity, potentially due to additional antiinflammatory properties of statins.
4170 19819943 IL-1beta is a master regulator of inflammation, and IL-1 receptor type I (IL-1RI) blockage improves glycemia and insulin secretion in humans with T2DM and in high-fat-fed mice pointing to a pivotal role of IL-1RI activity in intra-islet inflammation.
4171 19819959 Our results suggest tau modification caused by insulin dysfunction and hyperglycemia may contribute to the increased incidence of AD in diabetes.
4172 19819959 We hypothesize that type 1 and type 2 diabetes may contribute to AD through different mechanisms; in type 2 diabetes, hyperglycemia-mediated tau cleavage may be the key feature, whereas insulin deficiency may be the major contributing factor in type 1 diabetes.
4173 19822665 Analogous to the actions of insulin in higher vertebrates, those in Drosophila include expansion of the insect fat cell mass both by increasing the adipocyte number and by promoting lipid accumulation.
4174 19837872 JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion (GSIS).
4175 19841616 We report that curcumin dose-dependently eliminates insulin-induced HSC activation by suppressing expression of type I collagen gene and other key genes relevant to HSC activation.
4176 19846739 In addition, insulin increased IGFBP-2 and GH and decreased IGFBP-1 and -4 but did not alter total IGF-I, IGF-II, or IGFBP-3 levels.
4177 19850685 Short-term insulin deprivation and hyperglycemia had no effect on RBP4 levels and synthesis rates in T1D.
4178 19915586 Insulin mediates Na(+)/K(+)-ATPase alpha1- and alpha2-subunit translocation to the cardiac muscle plasma membrane via a PI3-kinase-dependent mechanism.
4179 19922611 Resistin, secreted from adipocytes, causes insulin resistance in mice.
4180 19934373 Therefore, we considered a deficiency in E2F-1 induces a decrease in regulatory T cells and an increase in auto-reactive T cells; however, the E2F-1 deficiency is not associated with T and B cells-independent dysfunction of pancreatic beta cell in insulin secretion.
4181 19936237 There is increasing evidence that insulin also plays a role in Alzheimer's disease (AD) as it is involved in the metabolism of beta-amyloid (Abeta) and tau, two proteins that form Abeta plaques and neurofibrillary tangles (NFTs), respectively, the hallmark lesions in AD.
4182 19938201 To investigate the association of obesity and elevated alanine aminotransferase with insulin resistance and compare these factors with metabolic syndrome.
4183 19940327 Adipose tissue produces multiple cytokines(TNF-alpha, IL-6, PAI-1, CRP, angiotensinogen, leptin, adiponectin, visfatin, apelin, resistin)which decrease insulin sensitivity and induce inflammatory processes, endothelial dysfunction,and atherosclerosis.
4184 19947814 The incretin effect, mediated by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), plays an important role in the regulation of insulin secretion in response to oral glucose.
4185 19947815 Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone from the incretin family, which stimulates insulin secretion and plays an important role in regulating the enteroinsular axis.
4186 19818665 These effects appeared to be independent of IRS-2, which is directly involved in insulin action.
4187 19854668 We measured LMF1 expression (mRNA) in Zucker diabetic rats (ZDF) throughout the development of obesity, insulin resistance and diabetes, and compared it with that of control rats.
4188 19854668 LMF1 expression was not altered in this experimental animal model of obesity, insulin resistance and diabetes in the presence of raised TG levels.
4189 19875458 Here, we report that STAT3 plays a key role in amino acid dampening of insulin signaling in hepatic cells.
4190 19875458 Replacement of the endogenous STAT3 with wild-type, but not S727A, recombinant STAT3 restored the ability of amino acids to inhibit insulin signaling, suggesting that Ser(727) phosphorylation was critical for STAT3-mediated amino acid effect.
4191 19875458 Finally, we found that STAT3 activity and the expression of its target gene socs3, known to be involved in insulin resistance, were both stimulated by excess amino acids and inhibited by rapamycin.
4192 19875458 In conclusion, our study reveals STAT3 as a novel mediator of nutrient signals and identifies a Ser(727) phosphorylation-dependent and Tyr(705) phosphorylation-independent STAT3 activation mechanism in the modulation of insulin signaling.
4193 19929783 Furthermore, tumor necrosis factor-alpha (TNF-alpha) and/or triglyceride accumulation-induced nuclear factor-kappaB (NF-kappaB) activation in the liver is shown to play a role in insulin resistance in patients with HCV-related chronic liver disease as well.
4194 19966489 In the BEC-treated diabetic animals, insulin induced a significant increase in plasma membrane GLUT4 and cytosolic tyrosine-phosphorylated IRS-1, indicating that it attenuates insulin resistance.
4195 20002081 Treatment with metformin increased the mean AUC (07.30-16.30 h) of plasma ghrelin by 24% (P= 0.003), while decreasing those of glucose by 19% (P < 0.001) and insulin by 19% (P= 0.001).
4196 20017397 The regulatory effects of insulin, insulin-like growth factor 1 (IGF-1), and relaxin on glucose-6-phosphate dehydrogenase (G6PDH) and glycogen synthase (GS) activities have been studied in myometrium of pregnant women of control group and with diabetes mellitus of different etiology.
4197 20017397 In the control group maximal stimulation of G6PDH activity was observed at 10(-9) M of peptides and their stimulating effect decreased in the following order: insulin > relaxin > IGF-1.
4198 20017397 In pregnant women with types 1 diabetes insulin effect on the enzyme activity was lower than in the control, and the effects of IGF-1 and relaxin were absent.
4199 20018749 Exposure to IL-1beta in fasting glucose activated multiple protein kinases that associate with the insulin gene promoter and transiently increased insulin gene transcription in beta cells.
4200 20018749 Under these conditions, IL-1beta caused the association of the same protein kinases, but a different combination of transcription factors with the insulin gene promoter and began to reduce transcription within 2 h; stimulatory factors were lost, RNA polymerase II was lost, and inhibitory factors were bound to the promoter in a kinase-dependent manner.
4201 20018750 In addition to improved adipokine, inflammatory, and lipid profiles, PPARgamma activation in mature adipocytes normalizes serum insulin without increased adipogenesis.
4202 20021538 Noninfectious systemic inflammation associated with adipocyte and adipose tissue macrophage cytokine production can also cause insulin resistance.
4203 20029537 We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation.
4204 20041157 We conclude that activation of Wnt/beta-catenin signaling in skeletal muscle cells improved insulin sensitivity by i) decreasing intramyocellular lipid deposition through downregulation of SREBP-1c; ii) increasing insulin effects through a differential activation of the Akt/PKB and AMPK pathways; iii) inhibiting the MAPK pathway.
4205 20079163 And we also observed that ABCC8 as well as the interaction between PPARG and HNF4A may contribute to post-challenge insulin secretion.
4206 20085121 The aim of this research was to study the influence of insulin resistance and adipocytokines in presurgical morbid obese patients on elevated serum alanine aminotransferase (ALT) as an indicator of NAFLD.
4207 20085121 Anthropometric parameters and insulin resistance are associated with elevated serum alanine aminotransferase in obese morbid patients with lower levels of adiponectin.
4208 19146426 Islet amyloid polypeptide (IAPP), a 37-amino acid polypeptide hormone of the calcitonin family, is colocalized and cosecreted with insulin in secretory granules of pancreatic islet beta cells.
4209 19146426 Its interactions with insulin in the secretory granules might influence the formation of cytotoxic oligomers and amyloid fibrils.
4210 19374389 Thiazolidinediones are insulin sensitizing drugs that target the peroxisome proliferator-activated receptor (PPAR) gamma.
4211 19462315 The effect of AT(1) receptor blockade on NOS expression and activity in humans with early insulin resistance syndrome (INSR) has not been previously investigated.
4212 18778861 Low skeletal muscle GLUT4 contributes to insulin resistance in CHF.
4213 19473183 The Transcription factor 7-like 2 (TCF7L2) rs7903146 gene polymorphism has been associated with risk of developing type 2 diabetes mellitus (DM), possibly by decreasing insulin secretion.
4214 19473183 To determine the impact of the TCF7L2 rs7903146 polymorphism on changes in insulin secretion and insulin sensitivity during 4 years of GH treatment in children born SGA.
4215 19556978 Thus, the major changes observed were among proteins involved in cytoskeletal rearrangement, insulin and calcium signaling, and inflammatory and redox signals that decisively upregulate GLUT4 granule trafficking in human adipose tissue.
4216 19664300 Since GLP-1 may increase insulin sensitivity and secretion, these results may provide a mechanism for the epidemiological association between high cereal fibre intake and reduced risk for diabetes.
4217 19699495 Fibroblast growth factor 21 (FGF21) has beneficial effects on glucose homeostasis and insulin sensitivity.
4218 19716569 Diverse single nucleotide polymorphisms (SNPs) of the IRS1 gene have been associated with insulin resistance and T2D risk.
4219 19680233 Recent genome-wide association studies (GWAS) in Asian Indians reported strong associations of variants near melanocortin-4 receptor (MC4R) and MLX interacting protein-like (MLXIPL) genes with insulin resistance and several obesity-related quantitative traits (QTs).
4220 19690071 Using tolerance tests, we found that, on an HFD, LXRbeta(-/-) mice enhanced their endogenous glucose production and became highly insulin resistant, whereas LXRalpha(-/-) and LXRalphabeta(-/-) mice remained glucose tolerant and insulin sensitive.
4221 19727657 Multiple linear regression analysis with adjustment for age and sex also showed that the plasma resistin level was significantly associated with serum concentrations of HDL-cholesterol, triacylglycerol and insulin, as well as with BMI.
4222 19727657 In addition, plasma resistin level was associated with dyslipidaemia, serum insulin concentration and obesity.
4223 19763711 We tested for site-specific differences in FTO gene expression in subcutaneous and visceral adipose tissue (SAT and VAT, respectively) from individuals with and without type 2 diabetes mellitus (T2D) and the relationships between fasting glucose, in vivo insulin action, and measures of adiposity with FTO gene expression in adipose tissue.
4224 19763711 Insulin action did not relate to SAT or VAT FTO mRNA expression.
4225 19765773 We aimed to determine whether insulin resistance or various biomarkers of cardiovascular risk have a role in the link between cystatin C and CVD in type 2 diabetes mellitus patients.
4226 19804472 In DM1 patients, leptin levels correlated with BMI, fasting insulin and insulin resistance (HOMA) (P < 0.01).
4227 19805579 FK506 binding protein 12.6 kDa (FKBP12.6), a protein that regulates ryanodine Ca(2+) release channels, may act as an important regulator of insulin secretion.
4228 19857477 RBP4, retinol and RBP4:retinol molar ratio were not different between the groups and were not associated with markers of insulin resistance.
4229 19880583 Insulin sensitivity correlated (r = x and y for IS(OGTT) and IS(HOMA,) respectively) with fasting maternal serum leptin (-0.44 and -0.52), IGFBP1 (0.42 and 0.39), and triglycerides (-0.31 and -0.27).
4230 19894030 Furthermore, the highest dose of aliskiren significantly attenuated the decreases in pancreatic islet insulin content and beta cell mass, and prevented pancreatic islet fibrosis in db/db mice, being associated with the reduction of 8-hydroxy-2'-deoxyguanosine-positive cells and Nox2 (also known as Cybb) expression in pancreatic islets by aliskiren.
4231 19896952 Furthermore, IDE exhibits a remarkable ability to preferentially degrade structurally similar peptides such as the selective degradation of insulin-like growth factor (IGF)-II and transforming growth factor-alpha (TGF-alpha) over IGF-I and epidermal growth factor, respectively.
4232 19918005 Improvement in postprandial glucose metabolism after gastric bypass is an immediate and direct consequence of the gastrointestinal rearrangement, associated with exaggerated GLP-1 release and independent of changes in insulin sensitivity, weight loss, and caloric restriction.
4233 19920090 In both crude and multivariate analyses, total adiponectin was inversely associated with insulin, proinsulin, C-peptide, HbA1c, sE-selectin, and C-reactive protein (CRP) levels.
4234 19920090 Total and HMW adiponectin are inversely associated with markers of insulin secretion/insulinemia, endothelial function, and inflammation.
4235 19923418 The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation.
4236 19933995 Insulin secretion stimulated by glucose, amino acids, and glucagon-like peptide-1 (GLP-1) was significantly elevated in the transgenic islets.
4237 19933998 Surprisingly, POMC-specific InsR knock-in increased energy expenditure and locomotor activity, exacerbated insulin resistance and increased HGP, associated with decreased expression of the ATP-sensitive K(+) channel (K(ATP) channel) sulfonylurea receptor 1 subunit, and decreased inhibitory synaptic contacts on POMC neurons.
4238 19933998 The contrasting phenotypes of InsR knock-ins in POMC and AgRP neurons suggest a branched-pathway model of hypothalamic insulin signaling in which InsR signaling in AgRP neurons decreases HGP, whereas InsR activation in POMC neurons promotes HGP and activates the melanocortinergic energy expenditure program.
4239 19933999 Cultured skeletal muscle cells were exposed to CB1 and/or CB2 pharmacological agonists/antagonists/inverse agonists, and the resulting effects on insulin-regulated phosphatidylinositol 3 kinase (PI 3-kinase)-protein kinase B (PKB) and extracellular signal-related kinases 1/2 (ERK1/2)-directed signaling were determined.
4240 19934000 The TCF7L2 variant rs7903146 appears to affect risk of type 2 diabetes, at least in part, by modifying the effect of incretins on insulin secretion.
4241 19934001 Only neutralizing antibodies against tumor necrosis factor-alpha (TNFalpha) attenuated KC-induced alterations in hepatocyte fatty acid oxidation, triglyceride accumulation, and insulin responsiveness.
4242 19937225 Adiponectin (r = 0.41, p < 0.0001), leptin (r = -0.36, p < 0.0001) and CRP (r = -0.30, p < 0.0001) during pregnancy were all associated with postpartum insulin sensitivity (determined using the insulin sensitivity index of Matsuda and DeFronzo [IS(OGTT)]).
4243 19944677 Both young and adult SHRs showed significant downregulated expression of PI3-kinase and decreased insulin-stimulated phosphorylations of Akt and eNOS in vascular tissues.
4244 19944677 Treatment with rosiglitazone (RSG), an insulin sensitizer, for 2 weeks increased vascular PPARgamma expression and restored PI3-kinase/Akt/eNOS-mediated signaling pathway only in young SHRs.
4245 19945428 To study the changes in secondary, tertiary, quaternary structures, and the alteration in the collective vibrational mode density of states during the amyloid fibrillation, bovine insulin in 20% acetic acid was incubated at 60 degrees C, and its multi-level structures were followed by various biophysical techniques, including circular dichroism (CD), thioflavin T fluorescence (ThT), dynamic light scattering (DLS), electron microscopy, and terahertz (THz) absorption spectroscopy.
4246 19952270 Interestingly, JNK inhibition did not prevent the palmitate-mediated cleaved caspase-3 increase, an apoptotic marker, or insulin signaling attenuation.
4247 19952270 However, pretreatment with the AMP kinase activator, aminoimidazole carboxamide ribonucleotide, blocked JNK phosphorylation and importantly prevented caspase-3 cleavage and restored insulin signaling during short-term exposure to palmitate.
4248 19966184 The binding of thrombin to its receptor stimulates inflammatory cytokines including IL-6 and monocyte chemoattractant protein-1 (MCP-1); both are associated with the development of insulin resistance.
4249 19966184 Because increased adiposity enhanced the expression of coagulation factor VII that stimulates the coagulation pathway in adipose tissue, we tested whether the inhibition of thrombin action ameliorates insulin resistance in obese diabetic (Lpr(-/-):db/db) mice.
4250 20016031 Furthermore, hemin reduced proteinuria/albuminuria and enhanced the depressed levels of adiponectin, AMP-activated protein-kinase, and glucose transporter-4 in SHRs, suggesting that although SHRs are normoglycemic, insulin signaling and renal function may be impaired.
4251 20022934 Paradoxically, JNK1 mutant mice feed less and lose more weight upon central administration of insulin, suggesting that JNK1 antagonizes insulin function in the brain.
4252 20023662 Here we show that NLRP3 interacted with thioredoxin (TRX)-interacting protein (TXNIP), a protein linked to insulin resistance.
4253 20042670 The islet in type 2 diabetes mellitus (T2DM) is characterized by a deficit in beta cells and islet amyloid derived from islet amyloid polypeptide (IAPP), a protein co-expressed with insulin by beta cells.
4254 20043882 Hence, in DEDD(-/-) mice, Akt protein levels are diminished in skeletal muscles and adipose tissues, which interferes with the translocation of glucose-transporter 4 (GLUT4) upon insulin stimulation, leading to inefficient incorporation of glucose in these organs.
4255 20043882 Such multifaceted involvement of DEDD in glucose homeostasis by supporting both insulin secretion (via maintenance of S6K1 activity) and glucose uptake (via stabilizing Akt protein), may suggest an association of DEDD-deficiency with the pathogenesis of type 2 diabetes mellitus.
4256 20068149 MKR mice harbor a transgene encoding a dominant-negative, kinase-dead human insulin-like growth factor-I receptor (IGF-IR) that is expressed exclusively in skeletal muscle, where it acts to inactivate endogenous insulin receptor (IR) and IGF-IR.
4257 20068149 Although lean female MKR mice are insulin resistant and glucose intolerant, displaying accelerated mammary gland development and enhanced phosphorylation of IR/IGF-IR and Akt in mammary tissue, in the context of three different mouse models of breast cancer, these metabolic abnormalities were found to accelerate the development of hyperplastic precancerous lesions.
4258 20074524 We tested whether leptin can ameliorate diabetes independent of weight loss by defining the lowest dose at which leptin treatment of ob/ob mice reduces plasma glucose and insulin concentration.
4259 20080751 Both HHEX and SOX4 have recently been implicated in pancreas development and the regulation of insulin secretion, but IRX3 had no prior association with pancreatic function or development.
4260 20081858 These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1).
4261 20082581 The treatment of type 2 diabetes mellitus (T2DM) has been revolutionized by the introduction of novel therapeutic regimens following the clinical approval of the long-acting basal insulin glargine 10 years ago, followed by insulin detemir and, more recently, agents that target the glucagon-like peptide (GLP)-1 system with dipeptidyl peptidase 4 (DPP-4)-resistant products, such as liraglutide and exenatide, and DPP-4 inhibitors, such as sitagliptin, saxagliptin, alogliptin, and vildagliptin.
4262 19128990 Glucagon-like peptide-1 (GLP-1) analogues and inhibitors of its degrading enzyme, dipeptidyl peptidase IV (DPPIV), are interesting therapy options in human diabetics because they increase insulin secretion and reduce postprandial glucagon secretion.
4263 19566830 Ghrelin is a multifunctional peptide hormone that affects various processes, including growth hormone and insulin release, appetite regulation, gut motility, metabolism and cancer cell proliferation.
4264 19576699 An impairment of glucose-stimulated insulin secretion--reflecting decreased glucokinase expression--and a moderate decrease in beta cell mass attributable to increased apoptosis, constitute the key features of beta cell failure in type 2 diabetes.
4265 19715772 Recent studies from our laboratory have identified several pathways implicated in fatty acid inhibition of insulin gene expression, including the extracellular-regulated kinase (ERK1/2) pathway, the metabolic sensor Per-Arnt-Sim kinase (PASK), and the ATF6 branch of the unfolded protein response.
4266 19217320 Despite this, Ex-4-treated mice demonstrated increased fractional insulin area (P=.035) and beta-cell proliferation as evidenced by elevated BrdU (P=.0001) and Ki67 staining (P=.04) with insulin co-localization.
4267 19395279 The toll-like receptor 4 (TLR4) and inducible nitric oxide synthase are proteins from the innate immune system that, when activated, can induce insulin resistance.
4268 19415164 Serum concentration of CRP was significantly correlated with BMI (gamma = 0.257, P < 0.01), WC (gamma = 0.293, P < 0.01), fat mass (gamma = 0.213, P < 0.01), total adipose tissue (gamma = 0.263, P < 0.01), visceral adipose tissue (gamma = 0.296, P < 0.01), insulin (gamma = 0.189, P = 0.047), PAI-1 (gamma = 0.206, P < 0.01), leptin (gamma = 0.322, P < 0.01), mean IMT (gamma = 0.132, P = 0.042), and HOMA-IR (gamma = 0.172, P = 0.045).
4269 19489767 In addition, a new functional role of orexin is emerging in the regulation of insulin and leptin sensitivities responsible for whole-body glucose metabolism.
4270 19489767 These suggest that hyperglycaemia due to insulin insensitivity during ageing or by habitual consumption of a high-fat diet leads to the reduction in orexin expression in the hypothalamus, thereby further exacerbating peripheral insulin resistance.
4271 19765959 RBP4 has been associated with insulin resistance and hypertriglyceridemia in obesity, the metabolic syndrome and type 2 diabetes.
4272 19875998 BMI and waist circumference, in separate models, explained significant variation in metabolic (insulin, lipids, blood pressure (BP)) and inflammatory/procoagulation (C-reactive protein, PAI-1 activity and antigen, and fibrinogen) risk factors.
4273 19913840 The C3 levels were associated significantly and linearly with serum triglycerides, waist circumference, and C-reactive protein (CRP), and inversely with current smoking but not with the marker of insulin resistance.
4274 19914265 Results of the present study suggest that inhibition of PI3K decreases activity and memory while increasing insulin resistance, depression, and anxiety.
4275 19327767 Variation in the HMGCR gene may influence component features of PCOS, including insulin resistance, SHBG, and free T.
4276 19184512 In group I, visfatin correlated with insulin concentration (r = 0.428, P = 0.023), HOMA-IR with esRAGE (r = -0.374, P = 0.049).
4277 19184512 Insulin resistance seems to be a link between esRAGE and visfatin in IHD diabetics.
4278 19656319 Low levels of sex hormone-binding globulin (SHBG) are associated with obesity, insulin resistance, and metabolic syndrome (MS) in men and women, and it has been suggested that SHBG could be a useful marker for MS risk.
4279 19708907 For both genders, glucosylated hemoglobin A1c (HbA1c), blood pH at diabetes onset, and pubertal status are the major factors determining the initial insulin dosage calculated as the amount of daily insulin per kilogram body weight (kg), the basal and prandial insulin dose per kilogram, and day and the insulin/carbohydrate ratios for meals.
4280 19850108 The level of expression of brain AQP9 is under the control of blood insulin concentrations, and its expression is increased in diabetes, suggesting that AQP9 could be involved in brain energy metabolism.
4281 20045145 Circulating vaspin levels are not significantly different between GDM, PE, and control subjects and do not correlate with insulin sensitivity in pregnant subjects.
4282 20045148 RNAi-mediated suppression of Ahi-1 resulted in increased glucose transport in rat L6 myotubes in both the basal and insulin-stimulated states (P < .01).
4283 20045149 Influence of insulin (0.02 micromol/L) on isometric twitch force was examined with and without blocking glucose transporter (GLUT) 4 translocation (latrunculin), sodium-coupled glucose transporter (SGLT) 1 (phlorizin, T-1095A), or PI3-kinase (wortmannin).
4284 20061534 Phosphatidylinositide 3-kinases (PI3Ks) play central roles in insulin signal transduction.
4285 20061534 By applying pharmacological inhibitors, transient overexpression and small-interfering RNA-based knockdown of PI3K and PKB/Akt isoforms, together with PI-lipid profiling and live-cell confocal and total internal reflection fluorescence microscopy, we now demonstrate that in response to insulin, PI3K-C2alpha generates PI(3,4)P(2), which allows the selective activation of PKBalpha/Akt1.
4286 20061534 Knockdown of PI3K-C2alpha expression and subsequent reduction of PKBalpha/Akt1 activity in the pancreatic beta-cell impaired glucose-stimulated insulin release, at least in part, due to reduced glucokinase expression and increased AS160 activity.
4287 20061534 Hence, our results identify signal transduction via PI3K-C2alpha as a novel pathway whereby insulin activates PKB/Akt and thus discloses PI3K-C2alpha as a potential drugable target in type 2 diabetes.
4288 20110336 We found that insulin resistance and agonist stimulation increased the expression and activity of MMPs (MMP-2 and MMP-7), the EGFR, contractile proteins such as myosin light chain kinase and MLC II, and their transcriptional activators including P90 ribosomal kinase (P90RSK) and serum response factor, possibly via the activation of extracellular signal-regulated kinase (ERK1/2) in VSMCs.
4289 20140850 CYP2J2 G-50T polymorphism may contribute to the pathogenesis of T2DM, partially by effects on insulin resistance, in patients with younger onset T2DM.
4290 20179320 Here we show that protein kinase C beta (PKCbeta) is a key mediator of insulin-mediated activation of hepatic SREBP-1c and its target lipogenic genes.
4291 20179320 The effect of PKCbeta inhibition was cancelled in insulin depletion by streptozotocin (STZ) treatment of mice.
4292 20200935 When untreated, primary IGF-1 deficiency may lead to a range of metabolic disorders, including lipid abnormalities, insulin resistance, and decreased bone density.
4293 20208057 ATM, mutated in ataxia telangiectasia, is critical for the genotoxic stress response, and its deficiency is associated with accelerated atherosclerosis and insulin resistance in humans and mice.
4294 20303812 An adipogenic medium stimulated moderate FAS and ACC1 expression in cells from both diabetic and non-diabetic animals, but glucose and insulin on their own had no such stimulatory action.
4295 20375212 Chemerin is a new adipokine involved in in vitro adipogenesis and insulin resistance and associates with body mass index (BMI) in vivo.
4296 20378848 Circulating IGF-1 correlated negatively with insulin resistance (homeostatic model assessment) (r=-0.1; P<0.0001) and was lower in participants with more components of the metabolic syndrome (Adult Treatment Panel III criteria) (P<0.0001).
4297 20382686 The six-transmembrane protein of prostate 2 (STAMP2) has been shown to be involved in insulin resistance in animal models, but in humans, its role is far from understood.
4298 20382773 Finally, in STZ-treated animals, UAG and Ob up-regulated insulin and Pdx1 mRNA and increased the expression of BCL2 similarly to AG.
4299 20390405 We propose that ACAD10 variation may increase type 2 diabetes susceptibility by impairing insulin sensitivity via abnormal lipid oxidation.
4300 20392866 These data indicate that MMP-9 is elevated in insulin resistance and is reduced by pioglitazone.
4301 20421289 Acute exercise improved insulin signalling, increasing insulin-stimulated Akt and Foxo1 phosphorylation and decreasing HNF-4alpha protein levels in the liver of DIO and ob/ob mice under fasting conditions.
4302 20421289 The present study shows that exercise acutely improves the action of insulin in the liver of animal models of obesity and diabetes, resulting in increased phosphorylation and nuclear exclusion of Foxo1, and a reduction in the Foxo1/HNF-4alpha pathway.
4303 20424140 Interestingly, a mild elevation of FFAs resulting from complete insulin deficiency also increased FGF-21 levels.
4304 20424140 These results from two independent human RCTs suggest that FFAs increase circulating FGF-21, while insulin is only of minor importance under physiological conditions.
4305 20460097 Less inhibition of insulin release was observed with two cell lines with less knockdown of SCOT.
4306 20460103 We found that ascofuranone improves ER stress-induced insulin resistance by activating AMPK through the LKB1 pathway.
4307 20515569 Double immunofluorescence labelling showed that ACE2 was co-localized with both insulin and somatostatin, while it was rarely co-localized with glucagon and pancreatic polypeptide.
4308 19940532 This acute condition could partly be reversed by discontinuation of intensive insulin therapy, whereby glycemia increased and serum IGF-1 concentration decreased [Ophthalmologica 2003;217:373-377].
4309 20200305 Changes in insulin secretion were directly related to the GIP responses to oral glucose (r = 0.64, P = 0.005), which were augmented in the obese-type 2 diabetic group and only moderately suppressed in the obese-NGT group.
4310 20222152 T2D is caused by a combination of insulin resistance and beta-cell failure and can be treated with insulin sensitizing drugs that target the nuclear receptor peroxisome proliferator-activated receptor (PPAR) gamma.
4311 20357360 In obese women, CD11c(+) ATM density was greater in subcutaneous than omental adipose tissue and correlated with markers of insulin resistance.
4312 20357360 Tissue culture medium conditioned by CD11c(+) ATMs, but not CD11c(-) ATMs or other stromovascular cells, impaired insulin-stimulated glucose uptake by human adipocytes.
4313 20357365 Despite unchanged body fat content, rats treated with intracerebroventricular FGF21 displayed a robust increase of insulin sensitivity due to increased insulin-induced suppression of both hepatic glucose production and gluconeogenic gene expression, with no change of glucose utilization.
4314 20357370 We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy.
4315 20368409 We sought to assess the associations of testosterones and sex hormone-binding globulin (SHBG) with metabolic syndrome and insulin resistance in men.
4316 20421298 The intestinal peptides GLP-1 and GIP potentiate glucose-mediated insulin release.
4317 20424231 Costaining of these factors in the islets of db/db mice clearly showed that MafA and insulin levels are decreased in c-Jun-positive cells.
4318 20424231 Consistent with these results, overexpression of c-Jun significantly decreased MafA expression, accompanied by suppression of insulin expression.
4319 20424231 Importantly, MafA overexpression restored the insulin promoter activity and protein levels that were suppressed by c-Jun.
4320 20424231 These results indicate that the decreased insulin biosynthesis induced by c-Jun is principally mediated by the suppression of MafA activity.
4321 20424231 It is likely that the augmented expression of c-Jun in diabetic islets decreases MafA expression and thereby reduces insulin biosynthesis, which is often observed in type 2 diabetes.
4322 20427484 In response to HF, FKBP52(+/-) mice demonstrated a susceptibility to hyperglycemia and hyperinsulinemia that correlated with reduced insulin clearance and reduced expression of hepatic CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a mediator of clearance.
4323 20428845 Although it is known that insulin regulate the activity of aromatase, there are few data about the effects of diabetes on this enzyme.
4324 20430894 We propose that the contrasting effects of acute and chronic stress on insulin sensitivity are driven by changes in subcellular distribution of MKP7 and activated JNK.
4325 20442404 Rspo1 also induced insulin mRNA expression in MIN6 cells.
4326 20442404 Rspo1 also stimulated insulin secretion in a glucose-independent fashion.
4327 20482500 Low serum adiponectin is associated with insulin resistance, atherogenic hyperlipidemia and arterial hypertension.
4328 20484464 In these animals, cevoglitazar also reduced fasting plasma insulin and, at the highest dose, reduced hemoglobin A1c levels by 0.4%.
4329 20490449 In this issue of Diabetologia, Wijesekara and colleagues, using a cell-specific Znt8 (also known as Slc30a8) knockout model, demonstrate that beta cell insulin processing and glucose tolerance is negatively affected after beta cell knock out of Znt8, whereas Znt8 knockout in alpha cells seems to have little effect on glucagon secretion or glucose tolerance.
4330 20508194 Lower levels of HMW adiponectin were significantly associated with type 2 diabetes, hypertension, higher body mass index, waist circumference, glucose, and insulin levels and lower high-density lipoprotein cholesterol levels.
4331 20519332 We also used INS-1 beta-cells and primary islets to analyze the roles of ATF3 in beta-cell function, including insulin gene expression and glucose-induced insulin secretion.
4332 20525362 Therefore, we investigated in a cohort of white European subjects at increased risk for type 2 diabetes whether genetic variation within the NR4A1 gene locus contributes to prediabetic phenotypes, such as insulin resistance, ectopic fat distribution, or beta-cell dysfunction.
4333 20530872 Loss of ABCG1 expression impaired insulin secretion both in vivo and in vitro, but it had no effect on cellular cholesterol content or efflux.
4334 20569275 As protein kinase C (PKC) activation is consistently present in skeletal muscle of obese and insulin resistant subjects, we generated a transgenic mouse model that overexpresses constitutively active PKC-beta(2) in skeletal muscle to test whether activation of PKC is sufficient to cause an aversive whole-body phenotype.
4335 20569275 Upon this genetic modification, increased serine phosphorylation in Irs1 was observed and followed by impaired (3)H-deoxy-glucose uptake and muscle glycogen content, and transgenic mice exhibited insulin and glucose intolerance as they age.
4336 20571309 Heparin and/or insulin stimulate lipoprotein lipase and are known to decrease serum triglyceride level.
4337 20578207 In this meta-analysis, we investigated the association of the FABP2 Ala54Thr polymorphism with insulin resistance and blood glucose.
4338 20578207 Our meta-analysis suggests that the Thr54 allele of the FABP2 Ala54Thr is weakly associated with a higher degree of insulin resistance, higher level of fasting insulin and higher level of 2-h BG.
4339 20588114 Blockade of IL-1 receptor with anakinra, the recombinant form of IL-1Ra, or neutralizing anti-IL-1beta antibodies, provides proof-of-principle data that reducing IL-1beta activity is sufficient for correcting dysfunctional beta-cell production of insulin in type 2 diabetes, including a possibility that suppression of IL-1beta-mediated inflammation in the microenvironment of the islet allows for regeneration.
4340 20592451 No SNP altered measures of insulin secretion or obesity, nor was BGLAP expression associated with rs1800247.
4341 19073347 In multiple regression analyses, BMI, age (inversely) and PEDF were independently correlated with homeostasis model assessment of insulin resistance (HOMA-IR).
4342 19382911 Prolactin regulatory element-binding (PREB) protein has been identified as a factor that regulates insulin gene expression in the pancreas.
4343 19636216 Insulin resistance (IR) is associated with intramyocellular lipid (IMCL) content and low serum adiponectin (ADP) levels and ADP is also involved in muscle fat oxidation.
4344 19861585 The recently discovered peptide apelin is known to be involved in the maintenance of insulin sensitivity.
4345 19861585 Fasting glucose, insulin, and adiponectin levels were determined on mice with generalized deficiency of apelin (APKO).
4346 19861585 APKO mice had diminished insulin sensitivity, were hyperinsulinemic, and had decreased adiponectin levels.
4347 20002564 Chemerin and vaspin are recently described adipocytokines with various suggested functions and potential to modulate inflammatory response and insulin resistance (IR).
4348 20070990 The other independent variants, like the final dose of gliclazide, homeostasis model assessment of insulin resistance, percentage change of prothrombin time, activated partial thromboplastin time, and total cholesterol, were not significantly associated with the percentage change of plasma PAI-1 level.
4349 20522596 Our results demonstrate that the intramyocellular accumulation of ceramide correlates strongly with the development of insulin resistance, and suggests that inhibition of SPT1 is a potentially promising target for the treatment of insulin resistance.
4350 20550176 Two compounds were able to increase cellular ATP levels, reduce caspase-3 activity and nitrite production, and increase glucose-stimulated insulin secretion in the presence of cytokines.
4351 20566664 In contrast, neither islet architecture nor insulin content was impacted by the loss of PANDER.
4352 20570944 Insulin-positive cells in dissociated mouse islets, required to restore euglycemia in chemically diabetic NOD-scid IL2rgamma(null) and spontaneously diabetic NRG-Akita mice, were quantified following transplantation via the intrapancreatic and subrenal routes.
4353 20584998 Although ghrelin reduces insulin secretion in rodents, its effect on insulin secretion in humans has not been established.
4354 20584998 The goal of this study was to test the hypothesis that circulating ghrelin suppresses glucose-stimulated insulin secretion in healthy subjects.
4355 20584998 This is a robust proof-of-concept study showing that exogenous ghrelin reduces glucose-stimulated insulin secretion and glucose disappearance in healthy humans.
4356 20610567 When expressed in Neuro2A and COS7 cells, an active form of GLP-1 was specifically detected by RIA in the conditioned medium of transduced cells, showed resistance to degradation by dipeptidyl-peptidase IV, and induced the secretion of insulin from NIT1 pancreatic beta-cells in vitro.
4357 20622162 In type 1 diabetes, the relative ratio of IE of [ring-(13)C(6)]phenylalanine in an older isoform versus pro-ApoA-1 was higher during insulin deprivation, indicating that de novo synthesized pro-ApoA-1 more rapidly accumulated damage, converting to mature ApoA-1.
4358 20637727 Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion.
4359 20648554 Polymorphisms in PNPLA3 have been linked to obesity and insulin sensitivity.
4360 20648554 CONCLUSION: Loss of Pnpla3 does not cause fatty liver, liver enzyme elevation, or insulin resistance in mice.
4361 20651004 These studies demonstrated that insulin directly influences ASBT expression and promoter activity and that ASBT function and expression are increased in rats with STZ-induced diabetes mellitus.
4362 20668022 Reduced body weight persisted and was associated with increased ARC leptin receptor binding and sensitivity to the anorectic effects of leptin, reduced adiposity, and enhanced insulin sensitivity in LL DIO rats fed chow until 10 wk of age.
4363 20675304 The expression of the three Tcf genes (Tcf7, Tcf7l1, and Tcf7l2) in the pancreas was reduced by treatment with insulin or high-fat diet feeding, in contrast to the stimulation of Tcf7l2 expression by insulin in the gut.
4364 20682281 Evidence from rodent models indicates that undercarboxylated osteocalcin (ucOC), a product of osteoblasts, is a hormone affecting insulin production by the pancreas and insulin sensitivity in peripheral tissues, at least in part through enhanced secretion of adiponectin from adipocytes.
4365 20682696 We examined in skeletal muscle whether the effects of leucine and glucose on these parameters and on insulin resistance are mediated by the fuel-sensing enzyme AMP-activated protein kinase (AMPK).
4366 20690636 Activation of the glucagon-like peptide-1 receptor (GLP-1R) upon ligand binding leads to the release of insulin from pancreatic cells.
4367 20719858 Therefore, FBPase plays an important role in regulating glucose sensing and insulin secretion of ?-cells and serves a promising target for diabetes treatment.
4368 20739649 The results of this study suggest that hyperinsulinemia and hyperglycemia caused by insulin resistance accelerate NP formation in combination with the effects of APOE epsilon4.
4369 20813088 Some authors showed that FTO gene polymorphism influences the food intake, energy expanditure and insulin resistance.
4370 20819415 It was hypothesized that resistance exercise decreases muscular adipose tissue and reduces the level of retinol-binding protein-4 (RBP4), which is linked to adipose tissue and insulin sensitivity in diabetics.
4371 20839851 Key alterations included inhibition of insulin translation and post-translational modifications in ER chaperones HYOU1 and HSPA5.
4372 20515643 In perigonadal and mesenteric WATs of KK-A(y) mice fed fucoxanthin, mRNA expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-? (TNF-?), which are considered to induce insulin resistance, were markedly reduced compared to control mice.
4373 20631025 We aimed to study circulating pigment epithelium-derived factor (PEDF) in vivo in association with insulin resistance and in vitro in human adipocytes.
4374 20631025 In all subjects, PEDF was positively associated with body mass index (r = 0.326; P < 0.0001), waist-to-hip ratio (r = 0.380; P < 0.0001), HbA(1c), and fasting triglycerides and negatively with insulin sensitivity (r = -0.320; P < 0.0001).
4375 20631025 Multiple linear regression analyses revealed that insulin sensitivity contributed independently to explain 14% of the variance in PEDF levels after controlling for the effects of body mass index, age, and log fasting triglycerides.
4376 20631025 Circulating PEDF is associated with insulin sensitivity.
4377 20693347 However, preservation of hepatic insulin sensitivity by n-3 LC-PUFAs required functional AMPK?2 and correlated with the induction of adiponectin and reduction in liver diacylglycerol content.
4378 20693347 Our results show that n-3 LC-PUFAs prevent hepatic insulin resistance in an AMPK?2-dependent manner and support the role of adiponectin and hepatic diacylglycerols in the regulation of insulin sensitivity.
4379 20716696 Activation of c-jun NH?-terminal kinase (JNK) was attenuated, and insulin signaling was improved in the liver of HFD mice.
4380 20724582 Chemerin reduced insulin-stimulated Akt1 phosphorylation and activation of 5'AMP-activated protein kinase (AMPK) in the skeletal muscle, but had no effect on Akt phosphorylation and insulin-stimulated AMPK activation in the liver and gonadal adipose tissue.
4381 20724582 Chemerin induces insulin resistance in the skeletal muscle in vivo.
4382 20739507 Diabetic mouse islets contain less active ERM, suggestive of a novel mechanism whereby impairment of insulin granule trafficking to the membrane through a complex containing F-actin, PIP2, Exo70, and ERM proteins contributes to defective insulin secretion.
4383 20739510 We conclude that impaired expression of PPARGC1A and other genes involved in mitochondrial function as well as a paradoxically increased response to insulin of genes involved in inflammation and ER stress may contribute to the development of insulin resistance induced by bed rest.
4384 20798332 Hypothalamic Angptl4 expression levels were increased upon food intake or administration of leptin, insulin, and nutrients.
4385 15944145 This study was designed to assess whether palmitate alters the expression and binding activity of the key regulatory factors pancreas-duodenum homeobox-1 (PDX-1), MafA, and Beta2, which respectively bind to the A3, C1, and E1 elements in the proximal region of the insulin promoter.
4386 15944145 Combined adenovirus-mediated overexpression of PDX-1 and MafA in islets completely prevented the inhibition of insulin gene expression by palmitate.
4387 15944145 These results demonstrate that prolonged exposure of islets to palmitate inhibits insulin gene transcription by impairing nuclear localization of PDX-1 and cellular expression of MafA.
4388 16050808 MafA binds to the insulin enhancer element RIPE3b (C1-A2), now designated as insulin MARE (Maf response element).
4389 16050808 Surprisingly, instead of interfering with each other's binding activity, the MafA and the A2-binding factors co-operatively activated insulin gene expression.
4390 16448557 Studies of DGAT1-deficient mice have helped to provide insights into the mechanisms by which cellular lipid metabolism modulates systemic carbohydrate and insulin metabolism, and a better understanding of how DGAT1 deficiency enhances energy expenditure and insulin sensitivity may identify additional targets or strategies for the treatment of obesity and type 2 diabetes.
4391 17928362 For example, in several mouse mutants, impairment of the growth hormone (GH)/IGF1 axis increases life span and also insulin sensitivity.
4392 18199433 Pax6 deficiency, as manifest in the Pax6(Sey-Neu) allele, reduced not only the number of cells expressing insulin or glucagon, but also the number of MafB, PDX-1 and MafA expressing cells.
4393 18199433 We show that MafB can directly activate expression of insulin and glucagon, and a MafB protein engineered to contain N248S mutation in the MafB (kr(ENU)) results in significantly reduced activation.
4394 18199433 Furthermore, pancreata from MafB deficient (kr(ENU)/kr(ENU)) mice exhibited reduced number of cells expressing insulin, glucagon, PDX-1 and MafA, with only a minor reduction in MafB expressing cells.
4395 18199433 These results suggest that MafB may function as a downstream mediator of Pax6 in regulating the specification of insulin and glucagon expressing cells.
4396 18199433 Interestingly, the remaining insulin(+) cells in these knockouts preferentially express Hb9, suggesting the existence of an alternate pathway for the generation of insulin expressing cells, even in the absence of Pax6 and MafB function.
4397 18199433 Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation.
4398 18288891 In these studies, we designed experiments to determine the contribution of Gsk-3beta to regulation of beta-cell mass in two mouse models of insulin resistance.
4399 18288891 Crossing these mice with those having haploinsufficiency for Gsk-3beta (Gsk-3beta+/-) reduced insulin resistance by augmenting whole-body glucose disposal, and significantly reduced beta-cell mass.
4400 18288891 To separate peripheral versus beta-cell-specific effects of reduction of Gsk3beta activity on preservation of beta-cell mass, mice homozygous for a floxed Gsk-3beta allele (Gsk-3(F/F)) were then crossed with rat insulin promoter-Cre (RIP-Cre) mice to produce beta-cell-specific knockout of Gsk-3beta (betaGsk-3beta-/-).
4401 18303668 Strict control of blood glucose by insulin could decrease VEGF expression in retina and protect retinal vessels from impairing in early STZ-diabetic rats.
4402 18338074 In mature beta-cells, PDX-1 transactivates insulin and other beta-cell-related genes such as GLUT2 and glucokinase.
4403 18370641 Insulin resistance (IR), the underlying cause of type 2 diabetes mellitus (DM), is also associated with elevated levels of inflammatory factors, such as C reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and fibrinogen.
4404 18370645 More recent data on experimental atherosclerosis in the mouse shows that (1) insulin administration reduces the number and the size of atherosclerotic lesions in apo E null mice and (2) in IRS-2 null mice, the interruption in insulin signal transduction results in enhanced atherogenicity.
4405 18370645 Our own most recent data show that a low dose infusion of insulin in patients with acute myocardial infarction induces a reduction in inflammation (C-reactive protein and serum amyloid A) and oxidative stress, and promotes fibrinolysis.
4406 18370662 The topics that are developed include the role of insulin and glucagon in lipolysis, control of lipoprotein lipase, the glucose-glycogen-gluconeogenesis interrelations, carbohydrate-protein interactions and ketosis.
4407 18370722 We evaluated whether leptin was associated with insulin resistance and MS after adjusting for confounders in Japanese-Brazilian women.
4408 18370722 Leptin was significantly correlated to BMI, fat mass, waist circumference, HOMA-IR, and insulin but not to other components of MS, such as fasting plasma glucose, blood pressure, HDL-cholesterol, triglyceride, and CRP levels.
4409 18370722 Conclusions: Adiposity-adjusted correlation of leptin with HOMA-IR and fasting insulinemia suggested that the former is associated with insulin resistance, despite the lack of independent association with the definition of the MS according to NCEP-ATP III.
4410 18370776 Low Hsps make organs vulnerable to injury, impair the stress response, accelerate systemic inflammation, raise islet amyloid polypeptide, and increase insulin resistance.
4411 18367663 These results indicate that insulin activates BK in the plasma membrane of MC and stimulates, via MAPK, an increase in cellular and plasma membrane BK-alpha.
4412 18555856 We measured basal and insulin-stimulated glucose uptake, glycogen accumulation, phosphoinositide 3 (PI-3) kinase activity, and Akt phosphorylation in primary skeletal muscle culture from subjects with type 2 diabetes mellitus incubated with or without various concentrations of PMI 5011.
4413 18599274 SIRT1 has been shown to regulate the expression of adipokines, repress the activity of factors required for maturation of fat cells, regulate insulin secretion, modulate plasma glucose levels and insulin sensitivity and alter mitochondrial capacity.
4414 18652694 We investigated the effect of a 12 vs. 48 hr fast on insulin action and skeletal muscle Munc18c and Syntaxin 4 protein in lean and obese subjects.
4415 18852336 We investigated the in vivo effects of insulin (hyperinsulinemia) on circulating lipocalin-2 levels by enzyme-linked immunosorbent assay via a prolonged insulin-glucose infusion.
4416 18852336 Also, in omental adipose tissue explants, insulin caused a significant dose-dependent increase in lipocalin-2 protein production and secretion into conditioned media (P < 0.05, P < 0.01, respectively); these effects were negated by both phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase inhibitors.
4417 18852336 Lipocalin-2 is upregulated by insulin via phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways.
4418 19219423 Exposure of endothelial cells to high glucose levels suppresses responses to insulin, including induction of endothelial nitric oxide synthase activity, through pro-inflammatory signalling via the inhibitor of nuclear factor kappaB (IkappaB)alpha-nuclear factor kappaB (NF-kappaB) pathway.
4419 19223654 Furthermore, when corrected for insulin content, isolated pancreatic islets from TxNIP(-/-) mice exhibited reduced glucose-induced insulin secretion.
4420 19220660 In rats with high fat-induced T2D, treatment with probucol improved insulin sensitivity, hepatic steatosis by raising circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro-inflammatory cytokines in the circulation and liver.
4421 19172665 Twenty-two plant extracts out of 133 were found to increase insulin-stimulated glucose uptake and 18 extracts were found to activate PPARgamma, 3 to activate PPARalpha and gamma, 6 to activate PPARdelta and gamma, and 9 to activate PPARgamma, alpha and delta.
4422 19732123 In an intraperitoneal glucose tolerance test, Zucker diabetic fatty rats receiving 2 mg GLP-1 Technosphere Powder (0.3 mg GLP-1) by pulmonary insufflation exhibited lower glucose concentrations and higher insulin concentrations than control rats.
4423 19779253 Gck and COX7A1 are the 2 examples in the present review to elucidate the epigenetic influence on the onset of diabetes. miRNAs are additional promising cellular components influencing both at transcriptional and translational levels and promoting either in favour or against (i.e., feed back) TFs, signaling factors and proteins through their pliotropic effects and thus are reported to regulate cellular physiology. miR-124a and miR-9 are primarily endemic to nervous tissue and they are now being exploited in islets for their function in executing exocytosis of insulin, which of course is one of the fundamental canons of diabetes. miR-375 persuades beta cells for glucose-induced insulin gene expression.
4424 19781106 Assessment of skeletal muscle insulin signaling demonstrated increased tyrosine phosphorylation of IRS-1 (p < 0.001) and increased IRS-1-associated phosphatidylinositol 3 (PI 3)-kinase activity (p < 0.001) following HC overfeeding.
4425 19817784 GPR119 is expressed in pancreatic beta-cells and enteroendocrine L-cells, and augments circulating insulin levels both through its direct insulinotropic action on beta-cells and through FA stimulation of glucagon-like peptide 1 (GLP-1) secretion.
4426 19817800 Until recently, cAMP was generally thought to potentiate insulin secretion through protein kinase A (PKA) phosphorylation of proteins associated with the secretory process.
4427 19878257 Glucagon-like peptide-1 (GLP-1) is an incretin hormone that is known to stimulate glucose-dependent insulin secretion.
4428 19878258 The incretin hormones, such as glucagon-like peptide-1 (GLP-1), induce the glucose-dependent secretion of insulin, improve beta-cell function and induce slowing of gastric emptying and feelings of satiety - which result in reduced food intake and weight loss.
4429 19920937 Incretin glucagon-like peptide-1 (GLP-1) is a hormone released from cells in the gastrointestinal tract (GI), leading to glucose-dependent insulin release from the pancreas.
4430 19557019 BRECs were then treated with 100 nM insulin for 24 h or not, and cells were prepared for the determination of VEGF mRNA expression by real-time PCR.
4431 19557019 Insulin or high glucose alone markedly increased VEGF mRNA and protein levels in BRECs (P<0.05, two-way ANOVA).
4432 19557019 However, the combination of insulin and high glucose displayed a weaker effect in promoting VEGF expression than did insulin alone (P<0.05, t-test).
4433 19557019 Pretreatment of cells with PI3-K inhibitor significantly (P<0.05, one-way ANOVA) suppressed the insulin-induced VEGF expression; neither pretreatment with the PKC inhibitor nor with the P42/p44 MAPK inhibitor showed an effect on the expression of VEGF at the mRNA or protein level (P>0.05, one-way ANOVA).
4434 19557019 Both insulin and high glucose can markedly increase VEGF expression in BRECs at the mRNA and protein level.
4435 19557019 We propose that insulin may upregulate VEGF expression through the PI3-K signalling pathway in BRECs, and high glucose may attenuate insulin-induced VEGF expression by impairing PI3-K signalling pathways.
4436 19708766 Adiponectin (ADN), an insulin-sensitizing adipokine, stimulates glucose uptake, inhibits gluconeogenesis, and plays an important role in improving insulin sensitivity.
4437 19811579 Linear regression analyses were performed to assess the association of the degree of iNOS expression in both the IMA and SV with the type of diabetes control (insulin, oral, diet), and the serum levels of HbAlc, glucose, free fatty acids (ffa), C-reactive protein (CRP), and low-density liproprotein (LDL) at the time of conduit harvest.
4438 19890025 Fasting insulin concentrations were best predicted by sc abdominal fat area in women (r(2) = 0.40; P < 0.01) and body mass index in men (r(2) = 0.53; P < 0.0001); adipocyte size did not contribute independently.
4439 19968882 Although activation of both PPARdelta and PPARgamma lead to increased insulin sensitivity and glucose tolerance, PPARdelta activation was functionally distinct from PPARgamma activation, and was characterized by increased hepatic and peripheral fatty acid oxidative metabolism, demonstrating the distinctive catabolic role of this receptor compared with PPARgamma.
4440 20007934 RLIP76 was induced by oxidative or hyperglycemic stress; the concomitant increase in insulin endocytosis was completely abrogated by inhibiting the transport activity of RLIP76.
4441 20007934 Because RLIP76 is induced by oxidative stress, it could play a role in insulin resistance seen in pathological conditions characterized by increased oxidative stress.
4442 20121885 Additionally, fasting plasma glucose, insulin and homeostatis model assessment of insulin resistance (HOMA-IR) significantly decreased while adiponectin increased over threefold [9.7 (3.7-17.7) vs. 38.0 (19.3-42.4) microg/ml] without any changes in resistin.
4443 20143027 As abnormal cellular glucose uptake and metabolism are partly involved in diabetic complications, this study was undertaken to explore the effect of hyperglycemia on glucose uptake, glucose transporter1 (GLUT1) expression induced by insulin of rat mandibular osteoblasts.
4444 20143027 The results showed that with 16.5mmol/L glucose, glucose uptake was not changed significantly, but GLUT1 expression was increased by 35% (P<0.01), insulin had no significant effect on glucose uptake, but it decreased GLUT1 expression by 33% (P<0.01).
4445 20143027 It is concluded that hyperglycemia can induce insulin resistance of osteoblasts, in which alteration in transport activity and function of GLUT1 might be involved.
4446 20151999 Furthermore, combination treatment resulted in an increased expression of insulin, pancreatic and duodenal homeobox 1 (PDX1) and glucose transporter 2 (GLUT2), and maintenance of normal beta/alpha-cell distribution in the pancreatic islet.
4447 20152736 Post-prandial GLP-1 and GIP levels increase after GBP and the incretin effect on insulin secretion normalizes to the level of non diabetic controls.
4448 20181095 Moreover, in this context, E2F1 transcriptional activity is regulated by glucose and insulin through the CDK4-dependent inactivation of the pRB protein.
4449 20005544 The aim of the study was to compare the regulation of ghrelin, leptin, and adiponectin by insulin and glucose during the second and third trimesters of pregnancy in women with diabetes.
4450 20005544 Fasting desacyl ghrelin concentrations decreased, whereas insulin and leptin concentrations increased, between the second and third trimesters of pregnancy (P < or = .011).
4451 20005544 During the clamp studies, desacyl ghrelin concentrations decreased by 33% (second trimester, P = .004) and 27% (third trimester, P = .09) with increasing glucose and insulin concentrations, whereas acyl ghrelin, leptin, and adiponectin concentrations were unaffected.
4452 20532020 Insulin secretory capacity was assessed, and the expression of Mn-SOD and Bcl-2 was measured by Western blotting.
4453 20535861 The synergistic action of unopposed oestrogen and leptin, compounded by increasing insulin, cortisol and xeno-oestrogen exposure directly initiate, promote and exacerbate obesity, type 2 diabetes, uterine overgrowth, prostatic enlargement, prostate cancer and breast cancer.
4454 20556572 Plasma ghrelin was not associated with systolic (P=0.981) or diastolic (P=0.724) BP, waist circumference (P=0.278), fasting insulin (P=0.246), fasting blood glucose (FBG) (P=0.693) and HOMA-IR (P=0.232).
4455 20416356 The free fatty acid (FFA) receptor GPR40, expressed by pancreatic beta-cells, may be responsible for insulin release following beta(3) adrenoceptor (Adrb3) activation.
4456 20416356 However, the magnitude of the insulin response after agonist treatment was decreased by approximately 50% in GPR40(-/-) mice.
4457 20416356 Our data indicate that insulin secretion, a secondary event following stimulation of Adrb3 receptors, is partially mediated by GPR40 and suggest that GPR40 is integral to the anti-diabetes effects of Adrb3 agonists.
4458 20519242 New intravenous or oral agents include the incretin glucagon-like peptide 1 (GLP1), its analogues, and dipeptidyl peptidase-4 inhibitors, which potentiate the activity of GLP1 and thus enhance glucose-dependent insulin secretion.
4459 20543712 In this study, the effects of renin inhibition on insulin resistance and adipose tissue dysfunction were explored in type 2 diabetic KK-A(y) mice.
4460 20580750 This study investigated the glucagon-releasing properties of the hormones glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) in 8 patients with type 1 diabetes mellitus (T1DM) without paracrine intraislet influence of insulin (C-peptide negative following a 5 g intravenous arginine stimulation; on study days only treated with basal insulin substitution).
4461 20590744 Taspoglutide showed typical effects of native GLP-1, with improvement in glucose tolerance, postprandial glucose, body weight, glycaemic control and insulin sensitivity.
4462 20590751 It can be concluded from the study that GLP-1 can induce reactive hypoglycaemia in pancreas transplant recipients through excessive insulin secretion associated with an increased insulin-to-glucagon ratio.
4463 20591095 There was a significant direct association between log CRP and both insulin use and daily dose for nonobese participants (beta=0.3, P=.03 and beta=0.01, P=.02, respectively) but not for obese participants (P=.8 and P=.5, respectively).
4464 20591095 Due to the association between insulin therapy and CRP in nonobese patients, these results may aid clinicians in deciding on the initiation of insulin therapy for nonobese diabetic patients when noninsulin alternatives are available.
4465 20617073 In obesity, inflammation develops when macrophages infiltrate adipose tissue and stimulate adipocyte secretion of inflammatory cytokines, that in turn affect energy balance, glucose and lipid metabolism, leading to insulin resistance.
4466 20075747 We analyzed whether fetal polymorphisms of the angiotensinogen (AGT) and angiotensin-converting enzyme genes influence birth weight and/or fetal total glycated hemoglobin (fTGH), a surrogate parameter of fetal insulin resistance at birth.
4467 20393450 The urinary TGF-beta1 level increased by 56% followed by a 23% decrease in the normal glucose tolerance group, changes that were significant and corresponded to the changes in the plasma glucose and insulin concentrations.
4468 20393450 Thus our results suggest that insulin contributes to increased TGF-beta1 production and possible early renal injury in prediabetic young African Americans.
4469 20650758 When PPAR gamma was specifically inhibited by GW9662 and PPARgamma-SiRNA, the protective effects of rosiglitazone and pioglitazone were almost undetectable, and the apoptotic rate increased and insulin secretion decreased to the level of the cytokine-treated cells.
4470 20658367 The mechanism may be associated with the increase of serum GLP-1 and ghrelin and the decrease of serum leptin and insulin resistance.
4471 20039889 Despite raising intact GLP-1 concentrations, treatment with sitagliptin did not alter either fasting or postprandial glucose, insulin or C-peptide concentrations.
4472 20381358 PTP1B, a non-transmembrane protein tyrosine phosphatase that has long been studied as a negative regulator of insulin and leptin signaling, has received renewed attention as an unexpected positive factor in tumorigenesis.
4473 20541824 Silencing iNOS by RNAi prevented the up-regulation of Bax and Fas induced by cytokine, thus reduced apoptosis of islets and recovered the insulin secretion index (3.43+/-0.24 vs 1.87+/-0.31, P<0.01).
4474 20577122 Finally, we assessed the role of phosphoinositol-3 kinase (PI3K) signaling pathway in mediating sympathetic activation to insulin in obesity.
4475 20577122 Notably, ICV pretreatment with a PI3K inhibitor (LY294002) blocked the increase in lumbar SNA induced by ICV insulin in lean and agouti obese mice.
4476 20600772 In the liver from diabetic treated group, the insulin-stimulated AKT phosphorylation was higher and the PEPCK protein levels were reduced.
4477 20627640 The lower fasting insulin levels and the impaired beta-cell function associated with IGF2BP2 SNPs are independent of obesity phenotypes.
4478 20684641 Insulin, coexpressed and cosecreted with hIAPP in vivo, has the capacity of interacting with hIAPP and further inhibiting the amyloid deposition of the peptide.
4479 20692406 We assessed the effects of A1AT supplementation (0.5 mg/mL; n = 4] on TCE activity, insulin levels, culture recovery, and islet quality.
4480 20692406 Addition of A1AT to impure islet preparations reduced protease activity and restored normal insulin levels as detected using enzyme-linked immunosorbent assay (ELISA) and SDS-PAGE of culture supernates.
4481 20692406 Culture of impure human islet fractions in the presence of A1AT prevented insulin cleavage and improved islet recovery.
4482 19733470 Microsomal triglyceride transfer protein (MTP) polymorphism modulates lipoprotein metabolism in the general population and liver disease in NASH; a functional MTP polymorphism recently predicted incident diabetes independently of insulin resistance in the general population.
4483 19775880 Our results indicate that daidzein enhances insulin-stimulated glucose uptake in adipocytes by increasing the expression of GLUT4 and IRS-1 via the activation of PPARgamma.
4484 20726228 DHSA may improve glucose tolerance and insulin sensitivity in KKAy mice and the effect might be related to the activation of PPAR-gamma by DHSA.
4485 20094041 Although silencing Jnk1 and/or Jnk2 prevented PA-induced inhibition of insulin signaling, it did not completely block decreased insulin-mediated glycogenesis, thus indicating JNK-independent pathways in the suppression of glycogenesis by PA.
4486 20094041 Muscle-specific inhibition of JNK2 (or total JNK) improves the capacity of NEFA utilization and glycogenesis, and is a potential therapeutic target for improving systemic insulin sensitivity in type 2 diabetes (T2D).
4487 20168308 In this study, we report that removal of melatonin receptor type 1 (MT1) significantly impairs the ability of mice to metabolize glucose and such inability is probably due to an increased insulin resistance in these mice.
4488 20186137 We investigated whether metformin or changes in metabolic measurements (weight, fasting plasma glucose (FPG), or fasting insulin (FI)) improved serum alanine aminotransferase (ALT) activity, as a marker for NAFLD, in the Diabetes Prevention Program (DPP).
4489 20798864 The aim of this study was to (1) determine the ability of metformin to attenuate IKKbeta action, (2) determine whether changes in AMPK activity are associated with changes in IKKbeta action in skeletal muscle, and (3) examine whether changes in AMPK and IKKbeta function are consistent with improved insulin signaling.
4490 20803707 The results showed that treatment with GlcN induced HIT-T15 cell death via apoptotic pathway, inhibited the expression of Bcl-2 and Bcl-xL, enhanced the expression of Bax, Bid and caspase-3, reduced the production of ATP and decreased in insulin secretion.
4491 20452774 Germ-line ablation of Jnk1 prevents both diet-induced obesity and insulin resistance.
4492 20466374 These effects likely contributed to improved insulin sensitivity, in an obese model, via prevention of adipocyte hypertrophy and adipocytokine dysregulation.
4493 20585935 The present study aimed to elucidate the mechanisms through which a high-fat diet (HFD) induces insulin resistance and insulin hypersecretion by focusing on the effects on enteroendocrine cells, especially those secreting glucose-dependent insulinotropic polypeptide (GIP).
4494 20601126 We hypothesized that Ang II inhibits the anti-mitogenic pathways while enhancing the mitogenic pathways stimulated by insulin via activation of Protein Tyrosine Phosphatase-1B (PTP-1B) in VSMC.
4495 20601126 We found that Ang II significantly inhibited insulin-induced phosphorylation of tyrosine 608 of IRS-1 and serine 473 of Akt, a downstream member of anti-mitogenic pathway of insulin.
4496 20601126 Activation of p42/p44 MAPK (a mitogenic pathway) induced by insulin was further enhanced by Ang II.
4497 20601126 Transfection of VSMC with PTP-1B antisense oligonucleotide markedly reduced the effects of Ang II on insulin signaling.
4498 20601126 We conclude that Ang II modulates both anti-mitogenic and mitogenic pathways of insulin via the activation of PTP-1B.
4499 20616094 Exendin-4, a glucagon-like peptide 1 (Glp-1)/incretin mimetic that stimulates beta-cell expansion, insulin secretion and normalization of blood glucose levels in diabetics, also promoted re-expression of Rgs16::GFP within a few days in pancreatic ductal-associated cells and islet beta-cells.
4500 20647474 The associations of the ABO blood group gene and NR5A2 gene variants with PC discovered by recent genome-wide association studies may link insulin resistance, inflammation, and thrombosis to pancreatic carcinogenesis.
4501 20655360 The present study was carried out to find the role of insulin in combination with pyridoxine on the concentrations of 5-HT and 5-HIAA, 5-HT receptor binding, 5-HTT gene expression and immunohistochemistry studies in the cerebral cortex and brainstem of streptozotocin induced diabetic rats. 5-HT content showed a significant decrease with a significant increase in 5-HIAA in cerebral cortex (p<0.01) and brain stem (p<0.001) in diabetic rats. 5-HT receptor binding parameters, B(max) and K(d), showed a significant decrease (p<0.001) in diabetic rats in cerebral cortex whereas in brainstem it showed a significant increase (p<0.001) compared to control.
4502 20711952 Insulin and 1,25-(OH)2D3 acted synergistically to increase estradiol production by 60% (p<0.005). 1,25-(OH)2D3 alone stimulated IGFBP-1 production by 24% (p<0.001), however, in the presence of insulin, 1,25-(OH)2D3 enhanced insulin-induced inhibition of IGFBP-1 production by 13% (p<0.009).
4503 20805279 This study assessed the effect of GLP1R polymorphisms on insulin secretion in response to hyperglycemia and to infused GLP-1 in nondiabetic subjects.
4504 20805279 Variation in GLP1R may alter insulin secretion in response to exogenous GLP-1.
4505 20809667 Of the incretin-based therapies, both the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists stimulate insulin secretion and inhibit glucagon secretion.
4506 20810672 In lung tissue, metformin did not activate AMPK but inhibited phosphorylation of insulin-like growth factor-I receptor/insulin receptor (IGF-1R/IR), Akt, extracellular signal-regulated kinase (ERK), and mTOR.
4507 20815278 TFLC can significantly decrease the blood levels of glucose and lipid and ameliorate oxidation stress in liver; its mechanism of action in improving insulin resistance might be related with its suppression on PTP1B expression in rat's liver to enhance the insulin signaling pathway.
4508 20630610 NF-kappaB binding was significantly positively associated with both BMI and homeostasis model assessment of insulin resistance (HOMA-IR).
4509 20667613 Angiotensin II receptor blockers (ARBs) have been shown to decrease insulin resistance in obese diabetic animal models and reduce the risk of new-onset diabetes in hypertensive patients.
4510 20689155 Recent findings that the pro-aging and pro-oxidant molecule p66shc contributes to S6K activation by nutrients and promotes insulin resistance and diabetes in mice may provide an answer to the "ROS or TOR?"
4511 20714510 This region binds PED/PEA15 with the same efficacy as D4 (K(D) approximately 0.7 microM) and, when transfected in different PED/PEA15-overexpressing cells, it is able to reduce PKC-alpha activity and to restore the sensitivity of PKC-zeta to insulin stimulation, independently of the PI3K/Akt signalling.
4512 20819535 To evaluate the association between the four adipokines, adiponectin, leptin, resistin and tumor necrosis factor-alpha (TNF-alpha) with insulin sensitivity, we used a hyperinsulinemic euglycemic clamp to test insulin sensitivity in Chinese patients with obesity and type 1 or type 2 diabetes mellitus versus controls.
4513 20819714 Several lines of evidence indicate that OGT attenuates insulin signal by O-GlcNAcylation of proteins involved in proximal and distal steps in the signaling pathway.
4514 20824098 In the present study, we found MyD88-deficient mice fed a HFD had increased circulating levels of insulin, leptin and cholesterol, as well as liver dysfunction (increased induction of ALT levels, increased activation of JNK and cleavage of PARP), which were linked to the onset of severe diabetes.
4515 20824239 In addition to improving insulin resistance and pancreatic ?-cell dysfunction, the GLP-1 agonists and DPP-4 inhibitors improve the impaired incretin response, as well as increase insulin secretion and reduce glucagon secretion, both in a glucose-dependent manner.
4516 18603624 Serum E-FABP levels, determined by an enzyme-linked immunosorbent assay in 479 Chinese subjects (age: 55.4 ± 13.5 years; M/F: 232/247), correlated positively (P < 0.05 to <0.001, age-adjusted) with parameters of adiposity, adverse lipid profiles, serum insulin, A-FABP, and C-reactive protein levels and were higher in subjects with the MetS (P < 0.001 vs. no MetS).
4517 20233149 When compared with NW, Ob displayed elevated F(2)-IsoP (99 ± 7 vs. 75 ± 4 pg/mL, p<0.005), IL-6 (2.2 ± 0.2 vs. 1.5 ± 0.3 pg/mL, p<0.005), elevated total leukocytes and neutrophils, altered levels of total cholesterol , low- and high-density-lipoprotein cholesterol, triglycerides, free fatty acids, glucose, and insulin (all p<0.005).
4518 20429050 While EMs improved the viability of islet induced by STZ, ALX or H(2)O(2), and EMs enhanced insulin accumulation of the cell supernatant after ALX and STZ stimulation.
4519 20690892 Recent studies have demonstrated the long-term therapeutic effects of central leptin gene therapy in obesity and diabetes via decreased insulin resistance and increased glucose metabolism.
4520 20833989 Serum adiponectin level was negatively correlated with body mass index (BMI), waist circumference, body fat percentage, and serum concentrations of insulin and triglyceride, and was positively correlated with high-density lipoprotein (HDL)-cholesterol level.
4521 20833989 Dietary intake may be indirectly associated with adiponectin levels through factors such as BMI, waist circumference, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride, HDL-cholesterol, and blood pressure.
4522 20842602 PPAR? also controls lipid catabolism and is the target of hypolipidaemic drugs, whereas PPAR? controls adipocyte differentiation and regulates lipid storage; it is the target for the insulin sensitising thiazolidinediones used to treat type 2 diabetes.
4523 20532620 Present study analysed effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the cortical GABA receptor binding, GABA(A?1), GABA(B) receptor subtype expression, GAD and GLUT3 expression.
4524 20620209 In hippocampal mitochondria, insulin-induced hypoglycemia increases the respiratory control ratio whereas both situations, hyper- and hypoglycemia, potentiate H(2)O(2) production and decrease the activity of MnSOD.
4525 20851291 There are reported associations between an angiotensin II type I receptor gene polymorphism (AT(1)R/A1166C) with hypertension, myocardial infarction, insulin resistance and cardiovascular disease risk.
4526 20859539 Dipeptidyl peptidase-4 (DPP-4) inhibitors improve pancreatic islet function by augmenting glucose-dependent insulin secretion and decreasing elevated plasma glucagon levels.
4527 20862393 Thus, GPR119 may represent an important new therapeutic target for the design of insulin secretagogues able to promote improvements in blood glucose control in patients with type 2 diabetes.
4528 20134415 Circulating IGFBP-2 was positively associated with insulin sensitivity, in agreement with previous studies.
4529 20134415 The association between IGFBP-2 expression and adiposity (r = 0.648; P < 0.05) was independent of insulin sensitivity (covariate).
4530 20134415 In conclusion, circulating IGFBP-2 was positively associated with insulin sensitivity.
4531 20580627 Adiponectin decreases with increasing adiposity and insulin resistance.
4532 20601896 Multiple regression analysis showed that waist circumference, diastolic blood pressure, 2-hour plasma insulin after glucose overload, and HbA1c were independently related factors influencing plasma chemerin levels.
4533 20601896 The present work indicates the potential link of chemerin with the pathogenesis of insulin resistance, obesity, and metabolic syndrome.
4534 20628088 Infant adiponectin at 12 months negatively correlated with maternal sCML (r = -0.467, P = 0.011), whereas high maternal sMGs predicted higher infant insulin or homeostasis model assessment (P = 0.027).
4535 20829391 When a dominant-negative mutant of SHIP2 was expressed in cultured neurons, insulin signaling was augmented, indicating physiological significance of endogenous SHIP2 in neurons.
4536 20829391 Neuroprotective effects of insulin and IGF-I were significantly attenuated in cultured cerebellar granule neurons from SHIP2 transgenic mice.
4537 20865670 Glis3 plays a key role in pancreatic development, particularly in the generation of ß-cells and in the regulation of insulin gene expression.
4538 20872961 The phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt axis is a key signal transduction node that regulates crucial cellular functions, including insulin and other growth factors signaling, lipid and glucose metabolism, as well as cell survival and apoptosis.
4539 20144013 In contrast, adipocyte monocultures did not exhibit any differences between insulin levels.
4540 20142631 Adiponectin and leptin are adipocytokines associated with insulin resistance.
4541 20543523 Stepwise regression analyses confirmed that the fetuin-A concentration was independently associated with the fasting insulin level and HOMA-IR, as were body mass index, triglyceride, LDL-cholesterol, leptin and adiponectin concentrations.
4542 20728534 Under both conditions, knockdown of CBR1 by specific siRNA increased ?-cell apoptosis, expression of lipogenic enzymes (such as ACC, FAS, and ABCA1), intracellular lipid accumulation, oxidative stress, ER stress, and nuclear SREBP1c, but decreased glucose-stimulated insulin secretion.
4543 20833146 Overexpression of Raldh3 reduced the insulin secretion in MIN6 cells, and surprisingly, increased the glucagon secretion in alphaTC1 clone 9 cells.
4544 20833146 These findings suggest that an increasing expression of Raldh3 deregulates the balanced mechanisms of insulin and glucagon secretion in the pancreatic islets and may induce ?-cell dysfunction leading to the development of type 2 diabetes.
4545 20923481 In the present study, we investigated the mechanism underlying HADHSC-mediated regulation of insulin secretion.
4546 20923481 Knockdown of HADHSC increased both fuel- (glucose or leucine plus glutamine) and non-fuel (high KCl)-induced insulin secretion.
4547 20923481 Enhanced glucose-stimulated insulin secretion (GSIS) induced by HADHSC knockdown was independent of changes in cytosolic Ca(2+) and also occurred in the presence of fatty acids.
4548 20923481 Insulin secretion promoted by both fuel and non-fuel stimuli is negatively regulated by HADHSC.
4549 20929506 The mechanism of action of cinnamic acid was determined using specific targets in the insulin signaling pathway, including protein tyrosine phosphatase (PTP) 1B, phosphatidylinositol 3-kinase (PI3-K) and the glucose transporter GLUT4.
4550 20929508 Hyperglycemia increases insulin-like growth factors (IGFs), especially IGF2, which acts via the IGF1 receptor present on renal cells.
4551 20929509 Serum levels of retinol-binding protein 4 (RBP4) are associated with insulin resistance and type 2 diabetes mellitus (T2DM) and may impact on ?-cell function.
4552 20929509 Serum RBP4 is correlated with glucose-stimulated insulin secretion in NGT non-VO subjects, but not in NGT VO subjects and T2DM patients.
4553 20549472 Studies over the last two decades have firmly established the importance of AKT in the regulation of cell survival, proliferation, and insulin-dependent metabolic cell responses.
4554 20686445 To investigate the mechanism of protection, we studied the effect of RS504393, a CCR2 antagonist, on insulin resistance and diabetic nephropathy in db/db mice.
4555 20728421 In vitro studies demonstrate that ET-1 is upregulated by insulin and glucose.
4556 20854065 We determined NOS activity in skeletal muscle of 7 T2DM and 8 nondiabetic control subjects under basal conditions and after a 4-h euglycemic insulin (80 mU/m2 x min) clamp.
4557 20854065 Plasma adiponectin was decreased in T2DM (4.5 +/- 0.8 vs. 7.0 +/-1.0 microg/mL, P < 0.02) and correlated with insulin-stimulated NOS activity (r = 0.49, P < 0.05) and with Rd (r = 0.50, P < 0.05).
4558 20854065 Decreased plasma adiponectin correlates with impaired insulin-stimulated NOS activity and severity of insulin resistance in T2DM.
4559 20868513 The present study was carried out to find the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT(2A) receptor subtype, gene expression studies on 5-HT(2A), 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed a significant decrease (p < 0.001) and a significant increase (p < 0.001) in 5-HIAA in hippocampus of diabetic rats compared to control. 5-HT receptor binding parameters B(max) and Kd showed a significant decrease (p < 0.001) whereas 5-HT(2A) receptor binding parameters Bmax showed a significant decrease (p < 0.001) with a significant increase (p < 0.05) in Kd in hippocampus of diabetic rats compared to control.
4560 20587146 Exendin-4 treatment and transduction of PDX-1 and NeuroD proteins by protein transduction technology into the cells induced insulin and pancreas-related gene expression.
4561 20736318 The forkhead transcription factor forkhead box O1 (Foxo1) plays a crucial role in mediating the effect of insulin on hepatic gluconeogenesis.
4562 20954972 By odds ratios lower risk to increased RRI is associated with higher serum albumin, higher hemoglobin, and FFM; greater risk is associated with hypertension, insulin resistance (HOMA ? 3.0), and renal insufficiency (GFR ? 90); coffee, assessed by number of cups/day, reduces risk.
4563 20956860 Adiponectin and visfatin are two cytokines which are considered to be possible links between obesity, insulin resistance and the metabolic syndrome.
4564 20699433 The coinfusion of insulin led to a total elimination of the increase in NOM, free fatty acids, and TBARS and a significant reduction in ROS generation by PMNLs and plasma MIF, visfatin, and myoglobin concentrations.
4565 20699433 Insulin did not affect TNF-?, MCP-1, IL-6, LBP, resistin, and HMG-B1 increases induced by the LPS.
4566 20713686 Higher serum fetuin-A was associated with abnormal albuminuria independent of BMI, waist circumference, homeostasis model assessment of insulin resistance, blood pressure, and other determinants of albuminuria in middle-aged and elderly Chinese women with NGT.
4567 20730455 Also, intracellular signaling is different with respect to insulin, with a prevalent activation of the ERK rather than the AKT pathway.
4568 21029300 This review highlights the particular importance of PERK-mediated translational control and the transcriptional response in pancreatic ?-cells and how these relate to the highly specialized function of ?-cells, namely glucose-regulated insulin secretion and production.
4569 21029313 Several recent studies have shown that Vhl deletion in ?-cells results in Hif1? activation, impaired glucose-stimulated insulin secretion (GSIS) and glucose intolerance.
4570 20584260 The aim of this study was to investigate effects of GIP and GLP-1 on gastric emptying and appetite after a mixed meal, and effects on insulin secretion and glucose disposal in humans.
4571 20660040 The liver-secreted protein Fetuin-A is elevated in insulin resistance, is an independent predictor of type 2 diabetes and is associated with atherosclerosis.
4572 20660040 Delta (?) Fetuin-A concentrations correlated with ?fasting insulin (r = 0.710; P = 0.001), ?2-h insulin (r = 0.693; P = 0.005), and HOMA-insulin resistance (r = 0.684; P = 0.001).
4573 20683642 To investigate the role of SOCS3 in porcine adipocyte insulin signaling, we first detected the effect of insulin on SOCS3 mRNA and protein expression in porcine primary adipocytes by real-time RT-PCR and Western blotting.
4574 20683642 The results showed that 100 nM insulin could induce SOCS3 mRNA expression but not protein expression, and overexpression of SOCS3 decreased IRS1 protein level, insulin-stimulated IRS1 tyrosine phosphorylation, PI3K activation, and Akt phosphorylation, but increased IRS1 serine phosphorylation in porcine primary adipocytes.
4575 20683642 These results indicate that SOCS3 is an important negative regulator of insulin signaling in porcine adipocytes.
4576 20942575 The present clinical trial examined the influence of a supplement, containing a combination of antioxidants extracted from fruit, berries and vegetables, on levels of plasma antioxidants (tocopherols, carotenoids and ascorbate), glycaemic control (blood glucose, HbA1c, insulin), oxidative stress biomarkers (F(2)-isoprostane, malondialdehyd, nitrotyrosine, 8-oxo-7, 8-dihydro-2'-deoxyguanosine, formamidopyrimidine glycosylase sites, frequency of micronucleated erythrocytes) and inflammatory markers (interleukin-6, C-reactive protein, prostaglandin F(2?)-metabolite) in type 2 diabetes.
4577 20972737 It has long been proposed that elevation of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and ?-glutamyltransferase (GGT) may be associated with insulin resistance (IR).
4578 20204603 In the weight loss study, the increase in circulating osteocalcin concentration (+70.6?±?29.3 vs. +32?±?13.5%, p?=?0.021) was significantly greater in subjects with the highest decrease in ALT levels, despite similar baseline BMI, insulin resistance and degree of weight loss than remaining subjects.
4579 20547473 To identify the relationship between insulin resistance and sympathetic activity, we examined muscle sympathetic nerve activity (MSNA) in controlled type 2 DM patients with alpha-glucosidase inhibitor (GI).
4580 20849903 Our goals were to study the proposed association of IL-2RA /CD25 with type 1 diabetes in the Belgian population over a broad age range, and to explore possible correlations with disease phenotypes, immune markers, HLA-DQ, INS, and PTPN22.
4581 20878480 Glucokinase is a key enzyme involved in regulating insulin secretion from the pancreatic ß-cell.
4582 20949340 Records were analyzed for patients with type 2 diabetes who had been initiated on biphasic insulin aspart 30 (BIAsp30) (n=632) or biphasic isophane human insulin 30 (BHI30) (n=762) and who had a glycated hemoglobin (HbA?(c)) measurement at baseline (up to 6 months before the index date) and end of study (6-12 months after index date).
4583 21060967 Expression of Ngn3 and NeuroD1 commits the cells to form endocrine pancreas, and to differentiate into subsets of cells that constitute islets of Langerhans. ?-cells in the islets transcribe gene-encoding insulin, and subsequently process and secrete insulin, in response to circulating glucose.
4584 21063111 The data presented show that insulin regulates MAPK, PI3K, PKC and NF-?B pathways, the expression of the inducible enzymes iNOS and COX-2, and the levels of NO, PGE(2) and IL-6 in the early phase of allergic lung inflammation in diabetic rats.
4585 20937249 G protein-coupled receptor (GPR) 119 is highly expressed in pancreatic ?-cells and enhances the effect of glucose-stimulated insulin secretion (GSIS) on activation.
4586 20937249 AS1535907 displayed an EC50 value of 4.8 ?M in HEK293 cells stably expressing human GPR119 and stimulated insulin secretion in rat islets only under high-glucose (16.8 mM) conditions.
4587 20937249 In conclusion, the GPR119 agonist AS1535907 induces a more rapid and physiological pattern of insulin release than glibenclamide, and represents a novel strategy for the treatment of type 2 diabetes.
4588 20952811 Global elevation of O-GlcNAc levels on intracellular proteins can induce insulin resistance, the hallmark of type II diabetes, in mammalian systems.
4589 21076579 The effects of adenovirus-mediated overexpression of TRB3 on insulin, PDX-1 and MafA gene expression in INS-1 cells were measured by Northern blot analysis.
4590 21076579 The treatment of INS-1 cells with tunicamycin and thapsigargin decreased insulin mRNA expression, but increased TRB3 protein expression.
4591 21076579 A transient transfection study showed that TRB3 inhibited insulin promoter activity, suggesting that TRB3 inhibited insulin gene expression at transcriptional level.
4592 21086586 It increases the circulating levels of incretin hormones (GLP-1, GIP), which contributes to amplify the insulin secretory response to meals and to reduce postprandial hyperglycaemia and, subsequently, fasting glycaemia.
4593 20483360 The relationship of psychological states (negative mood, life stress, and stress-responsive hormones) and adiponectin, an adipokine that promotes insulin sensitivity, was investigated in two separate studies.
4594 20648057 We aimed to evaluate the potential role of TCF7L2 gene polymorphisms on sympathovagal response in relation to changes in plasma insulin and/or GLP-1 concentration after glucose ingestion.
4595 20648057 In conclusion, TT genotype of rs12255372 and rs7903146 TCF7L2 gene variants is associated with lower insulin secretion and higher cardiosympathetic activity.
4596 20716056 Glycogen phosphorylase inhibitors that act in hepatocytes either exclusively by dephosphorylating GPa (e.g. indole carboxamides) or by allosteric inhibition of GPa (1,4-dideoxy-1,4-D-arabinitol) are very powerful experimental tools to determine the relative roles of covalent modification of glycogen phosphorylase and/or cycling between glycogen synthesis and degradation in the mechanism(s) by which insulin and neurotransmitters regulate hepatic glycogen metabolism.
4597 20840078 Experiments using specific COX and LOX (lipoxygenase) inhibitors demonstrated the importance of COX-1 activity for acute (20 min) stimulation of insulin secretion, suggesting that AA metabolites may be responsible for the insulinotropic effects.
4598 20847305 To determine whether obesity and insulin resistance associate with changes in the protein content of high-density lipoprotein (HDL) in 2 different groups of men by using targeted proteomics.
4599 21054880 We have examined whether saturated nonesterified fatty acids (NEFA) and insulin, which increase in concentration with developing insulin resistance, can trigger the production of interleukin (IL)-6 and tumor necrosis factor (TNF)-? in human monocytes.
4600 21054880 Monocytes incubated with insulin and palmitate together produced more IL-6 mRNA and protein, and more TNF-? protein, compared to monocytes incubated with palmitate alone.
4601 21054880 Incubation of monocytes with insulin alone did not affect the production of IL-6 or TNF-?.
4602 21084849 Oxygen consumption, insulin secretion, and the degree of central islet necrosis were measured in untreated and transfected islets to test the effects of cytoglobin on islet survival and function in vitro.
4603 21084849 The presence of cytoglobin reduced islet cell loss by reducing hypoxia related central islet necrosis and increased insulin secretion as compared with untreated islets.
4604 21085106 Glucose transporter type 4 (GLUT4) is the major transporter that mediates glucose uptake by insulin sensitive tissues, such as the skeletal muscle.
4605 21085106 Upon binding of insulin to its receptor, vesicles containing GLUT4 translocate from the cytoplasm to the plasma membrane, inducing glucose uptake.
4606 21085106 Reduced GLUT4 translocation is one of the causes of insulin resistance in type-2 diabetes.
4607 20855893 Specific blockade of ATF3 using siRNA or C-terminally deleted ATF3(?C) attenuated ethanol-induced pancreatic ?-cell apoptosis or dysfunction and restored the down-regulation of glucokinase (GCK), insulin, and pancreatic duodenal homeobox-1 induced by ethanol.
4608 20926583 Fasting blood glucose and insulin levels were significantly elevated in IGFBP-3(-/-) mice.
4609 20926583 During hyperinsulinemic clamps, IGFBP-3(-/-) mice had increased basal hepatic glucose production, but after insulin stimulation, no differences in hepatic glucose production were observed.
4610 20932285 Retinol binding protein 4 (RBP4) promotes insulin resistance in mice and is systemically elevated in patients with obesity and type 2 diabetes.
4611 20932285 The strong associations with hepatic and renal function, insulin resistance and acute mortality collectively suggest a role of RBP4 in the pathogenesis of critical illness, possibly as a negative acute phase reactant, and allow a proposition as a potential novel biomarker for ICU patients.
4612 20943795 Animal experiments suggest that circulating palmitoleic acid (cis-16:1n-7) from adipocyte de novo fatty acid synthesis may directly regulate insulin resistance and metabolic dysregulation.
4613 20850340 Genetic and cellular studies of Perk-deficient beta cells showed that PERK was crucially required for ER functions including proinsulin trafficking and quality control, unrelated to the ER stress pathway.
4614 20855122 IH also increased JNK1 activity and insulin receptor substrate 1/2 (IRS-1/2) serine phosphorylation, reduced insulin-stimulated IRS-1/2 tyrosine phosphorylation and Akt serine 473 phosphorylation, and induced hepatic insulin resistance.
4615 20855122 Taurine co-infusion with IH prevented the rise in 8-isoprostaglandin and MDA, inhibited the activation of JNK1, and improved insulin signaling and insulin resistance in liver.
4616 20855122 And this effect may be associated with the inhibition of JNK1 activation and the improvement of insulin signaling.
4617 20888657 A low serum adiponectin is also associated with insulin resistance.
4618 20888782 These findings, together with evidence for the involvement of JNK signaling in other manifestations of the metabolic syndrome such as obesity and insulin resistance, have suggested that JNK could be a novel therapeutic target in this disorder.
4619 20926102 Roscovitine or co-infection of dominant negative Cdk5 (dnCdk5) with p35 increased insulin secretion and inhibited apoptosis.
4620 20926386 We have used Drosophila melanogaster to determine whether O-GlcNAc metabolism plays a role in modulating Drosophila insulin-like peptide (dilp) production and insulin signaling.
4621 20964318 Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator in the process of insulin signaling and a promising drug target for diabetes and obesity.
4622 21094905 More recently, it has been also demonstrated that within the central nervous system, GLP-1 also exerts important metabolic actions inhibiting food intake, increasing insulin secretion, and modulating behavioral responses.
4623 21094906 The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), work together to reduce postprandial hyperglycemia by glucose-dependent insulin secretion and inhibition of glucagon release, as well as inhibition of GI motility and gastric emptying.
4624 21094907 The incretin glucagon-like peptide-1 (GLP-1) is a hormone that facilitates insulin release under high blood sugar conditions.
4625 21094910 The activation of GPR119 increases the intracellular accumulation of cAMP, leading to enhanced glucose-dependent insulin secretion from pancreatic ?-cells and increased release of the gut peptides GLP-1 (glucagon-like peptide 1), GIP (glucose-dependent insulinotropic peptide) and PYY (polypeptide YY).
4626 21103350 SNPs from DGKB, MADD and SLC30A8 were associated with fasting glucose while PROX1 rs340874 was significantly associated with OGTT 2-h glucose (p?=?0.0392?0.0014, adjusted for age, gender and BMI), the glucose-raising allele also showed association to lower insulin secretion.
4627 21105857 Dapagliflozin, a selective inhibitor of sodium glucose transporter 2 (SGLT2), targets hyperglycemia independently of insulin, via decreasing renal glucose reabsorption.
4628 21108535 Indeed, the complementation of NKX6.1 by ectopic PDX-1 expression substantially and specifically promoted insulin expression and glucose regulated processed hormone secretion to a higher extent than that of PDX-1 alone, without increasing the reprogrammed cells.
4629 21109190 Here we demonstrate that in insulin-deficient diabetic mice, there is a reduction in expression of the major transcriptional regulator of cholesterol metabolism, SREBP-2, and its downstream genes in the hypothalamus and other areas of the brain, leading to a reduction in brain cholesterol synthesis and synaptosomal cholesterol content.
4630 21109194 These defects were normalized by expression of a constitutively active form of Akt in the islets of ?DKO mice, preserving insulin secretion in response to glucose.
4631 21109194 The class IA PI3K pathway in ? cells in vivo is important in the regulation of insulin secretion and may be a therapeutic target for type 2 diabetes.
4632 20615270 PTP 1B is the physiological antagonist of the insulin signalling pathway.
4633 20802253 Furthermore, the impact of the interaction between genetic variation in TCF7L2 and glycemia on changes in insulin secretion was tested in 315 individuals taking part in a lifestyle intervention study.
4634 20802253 For the SNPs in TCF7L2 and WFS1, we found a significant interaction between glucose control and insulin secretion (all P ? 0.0018 for glucose × genotype).
4635 20802253 In the longitudinal study, rs7903146 in TCF7L2 showed a significant interaction with baseline glucose tolerance upon change in insulin secretion (P = 0.0027).
4636 20802253 For the diabetes risk genes TCF7L2 and WFS1, which are associated with impaired incretin signaling, the level of glycemia determines SNP effects on insulin secretion.
4637 20823098 Novel low molecular weight pyrimidine-based compounds that activate the GLP-1 receptor and stimulate glucose-dependent insulin secretion are described.
4638 20841609 Possible mechanisms by which high circulating SHBG prevents the development of type 2 diabetes involve regulation of fasting glycemia but not alteration of insulin secretory function.
4639 20841610 This is associated with insulin resistance and higher activation of iNOS and JNK in muscle and liver.
4640 20855545 Toll-like receptor 4 (TLR4) has been reported to induce insulin resistance through inflammation in high-fat-fed mice.
4641 20855545 Further studies showed that TLR4 deficiency had no effect on insulin signaling and muscle proinflammatory cytokine production in response to fasting.
4642 20871975 The incretin hormones gastric inhibitory polypeptide and especially glucagon-like peptide (GLP) have an important physiological function in augmenting postprandial insulin secretion.
4643 20876718 Suppressor of cytokine signaling (SOCS)-3 and protein-tyrosine phosphatase 1B (PTP-1B) are two endogenous inhibitors of tyrosine kinase signaling pathways and suppress both insulin and leptin signaling via different molecular mechanisms.
4644 20876720 Consistent with increased insulin sensitivity, mice with ablated hepatic leptin signaling had increased insulin-stimulated phosphorylation of Akt in the liver.
4645 20876720 These data reveal that unlike a complete deficiency of leptin action, which results in impaired glucose homeostasis, disruption of leptin action in the liver alone increases hepatic insulin sensitivity and protects against age- and diet-related glucose intolerance.
4646 20876720 Thus, leptin appears to act as a negative regulator of insulin action in the liver.
4647 20938636 In both groups, training-induced improvements in insulin-stimulated R(d) (~20%) were associated with increased muscle protein content of Akt, TBC1D4, ?2-AMP-activated kinase (AMPK), glycogen synthase, hexokinase II and GLUT4 (20-75%).
4648 20943756 Intracellular analysis using immunofluorescence showed colocalization of BACE1 with insulin and BACE2 with clathrin-coated vesicles of the plasma membrane in MIN6 cells.
4649 20953578 Our results demonstrate that the targeting of ERK1 could partially protect obese mice against insulin resistance and liver steatosis by decreasing adipose tissue inflammation and by increasing muscle glucose uptake.
4650 21051252 The fasting mean levels of IGFBP-1 were increased in both T1D with normal renal function (geometric mean: 216 ?g/l, range 169-275 ?g/l) and in T2D with CKD5D (geometric mean: 112 ?g/l , range 78-162 ?g/l, p=0.15 compared with T1D patients) in spite of a high mean insulin level (32±5 mU/l).
4651 21051252 Insulin caused a similar decrease (p<0.05 all groups) in IGFBP-1 mean levels for the first 90 min in the T2D patients with CKD5D (73±7% of basal IGFBP-1 values) and the T1D patients (69±6%) with normal renal function.
4652 21051252 After hemodialysis the IGFBP-1 serum levels increased compared with the levels at the end of insulin infusion but the predialysis values remained significantly lower than before the insulin infusion.
4653 21051252 After 90 min of insulin infusion a blunted decrease in IGFBP-1 was seen in T2D patients with CKD5D compared with type 1 diabetes with normal renal function.
4654 21059249 Here we analyzed the interaction of (pre)proinsulin with the best characterized chaperone of the hsp70 family, bacterial DnaK.
4655 21114601 AS1535907, a small molecule agonist of GPR119, was assessed for its glucose-stimulated insulin secretory activity and pancreatic ?-cell function in type 2 diabetes.
4656 21114601 As compared with the vehicle, gene expression analysis revealed that AS1535907 significantly upregulated transcription factors (Nkx 2.2, Nkx 6.1, NeuroD and activin A), responsible for ?-cell regulation and prohormone-converting enzyme 1 responsible for insulin biosynthesis.
4657 21117451 After 15 days treatment with GII (100 mg/kg body weight for 3 weeks) glycosylated hemoglobin came down and insulin increased to normal values in the sub-diabetic, moderately diabetic and severely diabetic rabbits.
4658 20861740 C-reactive protein (CRP) is an inflammatory marker associated with obesity, insulin resistance, and cardiovascular disease.
4659 21044991 Using MR, the authors also observed a positive association of GGT with insulin (? = 0.19, 95% CI: 0.01, 0.37; P = 0.04).
4660 21139139 Insulin and IGF-1 binding stimulates receptor tyrosine kinase activity and blocks apoptosis, whereas unliganded IR and IGF1R, acting through a mechanism independent of their catalytic activity, exert a permissive effect on cell death.
4661 19486109 Glucokinase (GK) in pancreatic beta cells is thought to be involved in insulin secretion and glucose homeostasis.
4662 18765678 Insulin, growth factors, and a variety of cellular stressors regulate mTORC1 by controlling Rheb GTP charging through modulating the activity of the tuberous sclerosis complex, the Rheb GTPase activating protein.
4663 20339002 Activated Rap1A promotes glucose-stimulated insulin secretion, islet cell hypertrophy, and islet cell proliferation, the latter exclusively through mammalian target of rapamycin complex 1, suggesting that Rap1 is an important regulator of beta-cell function.
4664 18155695 Experimentally-induced diabetes can modify the behavioral and neurochemical effects of drugs acting on dopamine systems, possibly through insulin-related regulation of dopamine transporter activity.
4665 20199785 Decreased gene expression of heat shock protein 72 (HSP72) in skeletal muscle is associated with insulin resistance in humans.
4666 20199785 We aimed to determine whether HSP72 protein expression in insulin-sensitive tissues is related to criterion standard measures of adiposity and insulin resistance in a young healthy human population free of hyperglycemia.
4667 20199785 In adipose tissue, HSP72 protein expression was not related to adiposity or insulin sensitivity.
4668 20596035 Parathyroid hormone (PTH) and vitamin D interactively regulate calcium fluxes across membranes, and thereby modulate insulin sensitivity, blood pressure, and arterial calcification.
4669 20736238 Whereas GLP-1 acts in the periphery to inhibit glucagon secretion and stimulate insulin release, it also acts in the central nervous system to mediate autonomic control of feeding, body temperature, and cardiovascular function.
4670 20733269 To investigate the molecular mechanisms of the effect of insulin, the expressions of neutral cholesteryl ester hydrolase (nCEH) and ATP-binding cassette transporter (ABC) G1 were analyzed.
4671 20733269 Insulin also suppressed the expressions of mRNA and protein for ABCG1.
4672 20832065 Changes in RBP4 saturation with retinol may link renal dysfunction and insulin resistance to atherosclerosis.
4673 20947509 We conclude that Igf1r signals primarily through Irs1 and affects insulin secretion, whereas ? cell proliferation is mainly regulated by InsR using Irs2 as a downstream signaling effector.
4674 20951125 GAGVGY increases both basal and insulin-stimulated glucose uptake through enhancement of GLUT1 expression and PI 3-K-dependent GLUT4 translocation, respectively.
4675 21073655 Importantly, decreased glucose-induced insulin expression and secretion in NIT-1 cells could be rescued via siRNA-mediated NOX2 reduction.
4676 21073655 Furthermore, high glucose concentrations led to apoptosis of ?-cells by activation of p38MAPK and p53, and dysfunction of ?-cells through phosphatase and tensih homolog (PTEN)-dependent Jun N-terminal kinase (JNK) activation and protein kinase B (AKT/PKB) inhibition, which induced the translocation of forkhead box O1 and pancreatic duodenal homeobox-1, followed by reduced insulin expression and secretion.
4677 21106865 In addition, unlike insulin or sulfonylureas, treatment with a GLP-1 receptor agonist or a DPP-4 inhibitor has not been associated with substantial hypoglycemia.
4678 21151568 A variant of the CDKAL1 gene was reported to be associated with type 2 diabetes and reduced insulin release in humans; however, the role of CDKAL1 in ? cells is largely unknown.
4679 21151568 Our results indicate that CDKAL1 controls first-phase insulin exocytosis in ? cells by facilitating ATP generation, K(ATP) channel responsiveness and the subsequent activity of Ca(2+) channels through pathways other than CDK5-mediated regulation.
4680 21152070 As shown by transgenic mouse models and by using phosphodiesterase 3 (PDE3) inhibitors, PDE3B has an important role in the regulation of insulin secretion in pancreatic ?-cells.
4681 21152264 Insulin stimulates glucose transport in muscle and adipose cells by stimulating translocation of glucose transporter 4 (GLUT4) to the plasma membrane.
4682 21152264 In a recent Cell Metabolism paper, Stenkula et al. found that insulin controls the spatial distribution of GLUT4 on the surface of isolated adipose cells through regulation of their post-fusion dispersal.
4683 21168694 Eighteen months after the combined graft, the FEV was 52%; the plasma C-peptide reached 0.79 ?g/L, the HbA(1c), 6% and the insulin requirements decreased to 55 U/d in the absence of hypoglycemic events.
4684 20713121 Then we present the current knowledge on how hormones regulate SCD1 expression with a particular interest on the role of insulin and leptin.
4685 20080359 I kappaB kinase-beta (IKK beta) is the upstream kinase that appears to be primarily responsible for NF-kappaB activation in these disorders; moreover, chronic IKK beta activation plays a prominent role in induction of insulin resistance in the metabolic syndrome.
4686 20553219 The objective of this study was to assess the association of serum leptin levels with insulin resistance (IR), metabolic syndrome (MetS), lipid levels, and glucose control in an Iranian type 2 diabetic population.
4687 21036943 The overall results are consistent with a unique Npc1 gene-diet interaction that promotes both weight gain and metabolic features associated with insulin resistance.
4688 21150588 Many recent studies are uncovering a role of des-acyl ghrelin in glucose metabolism specifically in modulating insulin sensitivity and glucose uptake into adipocytes.
4689 21150588 Ghrelin plays a role in regulating glucose homeostasis through the modulation of insulin secretion and insulin sensitivity.
4690 21176750 Inflammation plays an important role in insulin resistance, and adipocytokines, including tumor necrosis factor-alpha and leptin, can induce insulin resistance.
4691 21176750 For improvement in EPO response, insulin resistance may be a new target for treating HD patients.
4692 21179199 Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance.
4693 20943855 Cytomix-mediated mitochondrial dysfunction in INS 832/13 cells was evident by a significant loss of mitochondrial membrane potential (MMP) and upregulated caspase 3 activity.
4694 20962202 Akt phosphorylation following insulin stimulation in soleus muscle was significantly (25%) higher in Hypoxia than Control (P < 0.05).
4695 21088604 Endogenous heat shock proteins (HSP) are decreased in disease states associated with insulin resistance and aging.
4696 20300528 Resistin, secreted from adipocytes, causes insulin resistance in mice.
4697 20849951 Together, these novel findings reveal an important functional role for ?-arrestin-1 in the regulation of insulin secretion and ?-cell survival by GPCRs.
4698 20959116 Glucose-stimulated insulin secretion was enhanced in islets from male null mice as compared to male WT whereas this response in female Irs-2(-/-) islets was identical to that of female controls.
4699 20959116 The ability of ?(2)-adrenoceptor (?(2)-AR) agonists to inhibit insulin secretion was attenuated in male Irs2 null mice.
4700 20959631 Inhibition of Akt signalling leads to insulin resistance and type 2 diabetes, whereas hyperactivation of Akt promotes tumorigenesis.
4701 20959631 In this study, we investigate how modest changes in the activity of the Akt signalling pathway, to an extent that might be achieved by drug treatment, would impact on insulin resistance and tumorigenesis.
4702 20959631 Using insulin-resistant PDK1(K465E/K465E) PH domain knock-in mice, we found that introducing the PTEN(+/-) mutation to slightly stimulate Akt restored normal insulin sensitivity.
4703 21129350 Glucagon-like peptide-1 (GLP-1) and its analogs are associated with a gamut of physiological processes, including induction of insulin release, support of normoglycemia, ?-cell function preservation, improved lipid profiles, and increased insulin sensitivity.
4704 18023664 Myocardial expression of anti-angiogenic proteins, angiostatin and endostatin, showing a 4.3- and 3.6-fold increase in diabetic animals respectively (both P < .01 vs ND), was markedly reduced in insulin-treated animals (2.3- and 1.8-fold vs ND; both P < .01).
4705 20970873 Serum OPG levels were associated with obesity, insulin resistance, serum CRP and carotid IMT.
4706 21074472 Thus, OGT attenuates insulin signal by O-GlcNAcylation of proteins involved in proximal and distal steps in the PI-3 kinase signaling pathway.
4707 21145457 IP7 affects this pathway by potently inhibiting the PDK1 phosphorylation of Akt, preventing its activation and thereby affecting insulin signaling.
4708 21146880 Here we found that the expression of miR-15a was up-regulated in the presence of high glucose for 1h, whereas prolonged periods of high glucose exposure resulted in depressed expression of miR-15a, and the change in expression levels of miR-15a coincided with insulin biosynthesis.
4709 18487451 These data suggest that the arcuate GLP-1 receptors are a key component of the GLP-1 system for improving glucose homeostasis by regulating both insulin secretion and glucose production.
4710 20849865 These studies suggest that NEP plays a role in regulating nerve function in insulin-deficient diabetes and DIO.
4711 20864515 Prep1 overexpression in HepG2 liver cells upregulated SYP and SHP1 and inhibited insulin-induced IR and IRS1/2 phosphorylation and was accompanied by reduced glycogen content.
4712 20864515 In Prep1 overexpressing cells, antisense silencing of SHP1, but not that of SYP, rescued insulin-dependent IR phosphorylation and glycogen accumulation.
4713 20864515 SHP1, a known silencer of insulin signal, is a transcriptional target of Prep1.
4714 20864515 In liver, transcriptional activation of SHP1 gene by Prep1 attenuates insulin signal transduction and reduces glucose storage.
4715 20870970 Suppression of Kinesin-1 by antisense oligonucleotides, or overexpression of dominant-negative acting kinesin heavy chain, has been reported to affect the sustained phase of glucose-stimulated insulin secretion in ?-cells in vitro.
4716 20870970 However, compared with controls, pancreas of Kif5b(fl/)?:RIP2-Cre mice exhibited both reduced islet size and increased islet number, concomitant with an increased insulin vesicle density in ?-cells.
4717 20870970 In addition to being essential for maintaining glucose homeostasis and regulating ?-cell function, Kif5b may be involved in ?-cell development by regulating ?-cell proliferation and insulin vesicle synthesis.
4718 20876716 We generated six class I and two class III VNTR constructs linked to the human insulin basal promoter or SV40 heterologous promoter/enhancer and demonstrated that AIRE protein modulates the insulin promoter activities differentially through binding to the VNTR region.
4719 20876716 Here we show that in the presence of the autoimmune regulator (AIRE), the class III VNTR haplotype is responsible for an average of three-fold higher insulin expression than class I VNTR in thymic epithelial cells.
4720 20876716 Further, the transcriptional activation of the INS-VNTR by AIRE requires the insulin basal promoter.
4721 20876716 These findings demonstrate a type 1 diabetes predisposition encoded by the INS-VNTR locus and a critical function played by AIRE, which constitute a dual control mechanisms regulating quantitative expression of insulin in human thymic epithelial cells.
4722 20876717 Consistent with a role for VAMP8 in the endocytosis of the insulin-responsive GLUT4, sarcolemma GLUT4 protein levels were increased in both the basal and insulin-stimulated states without any significant change in the total amount of GLUT4 protein or related facilitative glucose transporters present in skeletal muscle, GLUT1, GLUT3, and GLUT11.
4723 20921208 These results indicate that TRPM2 is involved in insulin secretion stimulated by glucose and that further potentiated by incretins.
4724 20929976 Insulin-induced egr-1 mRNA in HTC-IR cells was associated with corecruitment of IR signaling cascade (IR, SOS, Grb2, B-Raf, MEK, and ERK) to this gene.
4725 20943749 Interestingly, rosiglitazone treatment improved insulin sensitivity and reduced FTO expression in muscle from type 2 diabetic patients.
4726 20971965 These results indicate that PSGL-1 is a crucial adhesion molecule for the recruitment of monocytes into adipose tissues in obese mice, making it a candidate for a novel therapeutic target for the prevention of obesity-related insulin resistance.
4727 21042792 NR1H2 rs2248949 was nominally associated with OGTT-derived first-phase insulin secretion and proinsulin conversion to insulin and significantly associated with the AUC of insulin levels during the IVGTT (p?=?0.007) after adjustment for age, gender, BMI and insulin sensitivity in the dominant model, with the minor allele conferring reduced pancreatic ?-cell function to the carriers.
4728 21042792 In subjects of European ancestry at increased risk for type 2 diabetes, common variation within the NR1H2 gene impaired insulin secretion, which may facilitate the development of type 2 diabetes.
4729 21047791 Insulin-dependent glucose homeostasis is highly sensitive to the levels of insulin-responsive glucose transporter 4 (GLUT4) expression in adipocytes.
4730 17130482 We report here a stable isotope flux phenotyping study of this "silent" phenotype, in which tissue-specific insulin effects in whole-body Pten(+/-)-deficient mice were dissected in vivo.
4731 20586612 Knockout of SOD1 downregulated the foxhead box A2/pancreatic and duodenal homeobox 1 pathway in a superoxide-dependent fashion at epigenetic, mRNA, and protein levels in islets, but improved insulin signaling in liver and muscle.
4732 20618069 Although knockouts of Gpx1 and Sod1 each alone or together decreased pancreatic ? cell mass and plasma insulin concentrations, these knockouts improved body insulin sensitivity to different extents.
4733 21072680 It also diminished insulin-stimulated tyrosine phosphorylation of IRS-1, PI3K (p85), and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, P38, and JNK.
4734 21076856 IGF I at low doses (0.3 nmol/l and above) or insulin at higher doses (1 nmol/l and above) stimulated 2DG uptake and [(3)H] thymidine incorporation into DNA. 2DG transport was enhanced already after 30 min of IGF I treatment whereas the effect of PTH became significant after 6 h.
4735 21123564 These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes.
4736 21209957 Our results show that palmitate and oleate (0.5 mmol/L, 48 h) induced JNK activation and AKT inhibition which resulted in decreased phosphorylation of FOXO1 following nuclear localization and the nucleocytoplasmic translocation of PDX-1, leading to the reducing of insulin and ultimately dysfunction of pancreatic NIT-1 cells.
4737 20978738 In this study, we tested the relative contribution of dysregulated glucagon secretion and reduced insulin release in the development of hyperglycaemia and type 2 diabetes by using synaptotagmin-7 knockout (KO) mice, which exhibit glucose intolerance, reduced insulin secretion and nearly abolished Ca(2+)-stimulated glucagon secretion.
4738 21039728 Leptin stimulated RBP-4 secretion ex-vivo, whilst insulin did not affect RBP4.
4739 21104068 In previous studies we determined that aristaless-like homeobox 3 (ALX3) is produced in islet cells, binds to the promoter of the insulin gene and regulates its expression.
4740 21104068 ALX3 deficiency resulted in increased blood glucose levels and impaired glucose tolerance in the presence of normal serum insulin concentrations.
4741 21116606 Moreover, they show that metformin enhances the expression of the genes encoding the receptors for both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in mouse islets and also increases the effects of GIP and GLP-1 on insulin secretion from beta cells.
4742 21212525 Butein prevented cytokine-induced NO production, iNOS expression, and NF-?B translocation and inhibition of glucose-stimulated insulin secretion (GSIS).
4743 9775125 OBJECTIVES AND JUSTIFICATION: To describe facilitated diffusion glucose transporters (GLUT) in humans, and particularly the regulation of GLUT4 expression since it is predominantly responsible for insulin-mediated glucose transport in muscle and adipose tissue, and plays a crucial role in whole-body glucose homeostasis.
4744 19822133 We determined by immunoblotting and immunohistochemistry that insulin treatment prevented the decrease of GFAP expression detected in the cerebral cortex, hippocampus, and cerebellum of untreated, diabetic rats.
4745 10756782 IDDM has, because of insulin lack, raised levels of triglycerides and afferent lipoproteins.
4746 12092185 IDDM has, because of insulin lack, increased levels of triglycerides and afferent lipoproteins.
4747 19966034 PPARgamma and PGC-1alpha mRNA expression in both fat depots as well as in skeletal muscle is associated with markers of insulin resistance and cardiovascular risk.
4748 19966034 Gene expression of PPARgamma and PGC-1alpha in human adipose tissue is related to markers of insulin resistance and cardiovascular risk.
4749 19966034 Increased muscle and adipose tissue PPARgamma and PGC-1alpha expression in response to physical training may mediate the beneficial effects of exercise on insulin sensitivity.
4750 20552313 Chronic stress and hypercortisolaemia are conditions, which have been suggested to be causal for Alzheimer's disease (AD) as brain insulin resistance is associated with ?-Amyloid-accumulation and hyperphosphorylation of tau-protein.
4751 20687123 To evaluate the influence of maternal insulin-dependent diabetes mellitus (IDDM) on maternal serum free ß-hCG, pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency (NT) thickness from 11 weeks to 13 weeks 6 days of gestation in a large cohort of women screened prospectively for chromosomal anomalies.
4752 20981553 In contrast, in hearts from HFD-induced insulin resistance rats, EPO decreased infarct size (18.66 ± 1.99 and 34.62 ± 3.41% in EPO-treated and untreated HFD rat hearts, respectively, p < 0.05) and increased phosphorylation of Akt, ERK1/2, and GSK-3?.
4753 21079817 According to the literature in the field, several cell types like ?-cell, myocyte, hepatocyte and/or adipocyte, as well as related complex signaling environment involved in peripheral insulin sensitivity are believed to be central in this pathology.
4754 21162749 Diabetic CAECs have enhanced inflammatory responses to stimulation of TLR2 or TLR4, and insulin alone is insufficient to correct the hyper-inflammatory responses.
4755 21194578 The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 (GLP-1), which are secreted by cells of the gastrointestinal tract in response to meal ingestion, exercise important glucoregulatory effects, including the glucose-dependent potentiation of insulin secretion by pancreatic ?-cells.
4756 21060146 These results suggest that lost cell-extracellular matrix interactions in cell encapsulation systems can lead to decreased insulin secretion and ILK signaling is a target to overcome this phenomenon.
4757 16955209 The aim of this study was to examine whether genetic variation in ADIPOQ, ADIPOR1 and ADIPOR2 may contribute to increased susceptibility to components of the insulin resistance syndrome (IRS).
4758 16955209 Of the eight SNPs examined in the ADIPOQ gene, rs4632532 and rs182052 exhibited significant associations with BMI (p=0.029 and p=0.032), fasting specific insulin (p=0.023 and p=0.026), sum of skin folds (SS) (p=0.0089 and p=0.0084) and homeostasis model assessment of insulin sensitivity (HOMA-%S) (p=0.015 and p=0.016).
4759 17426313 We examined the genetic association of neuropeptide Y receptor Y5 (NPY5R) single nucleotide polymorphisms (SNPs) with measures of the insulin resistance (metabolic) syndrome.
4760 18633101 TLR4 muscle protein content correlated with the severity of insulin resistance.
4761 18633101 CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans.
4762 19633828 TACE expression, and TACE, TNF-alpha, TNFR1 and IL-6R levels were increased in type 2 diabetes, and positively correlated with insulin resistance.
4763 19633828 A 6 h lipid infusion into NGT individuals decreased insulin-stimulated glucose metabolism by 25% with increased TACE, decreased expression of the gene encoding TIMP3 and increased IL-6R release.
4764 19633828 TACE activity was increased in skeletal muscle of obese type 2 diabetes patients and in lipid-induced insulin resistance.
4765 19966211 We sought to incorporate this characteristic into an HLA-transgenic model of the disease and to determine the influence of reduced thymic insulin expression on CD8+ T cell responses to preproinsulin.
4766 19966211 Our results suggest that insulin alleles that predispose to type 1 diabetes in humans do so, at least in part, by facilitating CD8+ T cell responses to the protein.
4767 21138825 Insulin replacement in diabetes often requires prandial intervention to reach hemoglobin A?(c) (HbA?(c)) targets.
4768 20663687 In fact, increased insulin, IGF-I and IGF-II levels are associated with tumor growth in vitro, in animal models, and in epidemiological studies in humans.
4769 20952489 Therefore, the present study addressed the effects of obesity-induced insulin resistance on the activity of the ubiquitin ligases, nuclear factor-B, p38 MAPK and phosphoinositide 3-kinase signalling pathways in the gastrocnemius muscle and compared these with muscle of standard chow-fed control rats.
4770 21070190 Taken together, these results suggest that the FTO protein may play a hitherto unrecognized role in the control of first-phase insulin secretion in pancreatic ?-cells.
4771 21211036 In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS associated with reduced measures of serum insulin at 30 min following an oral glucose load (per allele effect (?) = -3.8% (-6.3%;-1.3%), P = 0.003), reduced incremental area under the insulin curve (? = -3.6% (-6.3%;-0.9%), P = 0.009), reduced acute insulin response (? = -2.2% (-4.2%;0.2%), P = 0.03), and with increased insulin sensitivity ISIMatsuda (? = 2.9% (0.5%;5.2%), P = 0.02).
4772 21211036 The C-allele was not associated with T2D in the case-control analysis (OR 1.07, 95% CI 0.96-1.18, P = 0.21). rs11161510 of ACADM did not associate with any indices of glucose-stimulated insulin release or with T2D.
4773 21246010 The human Rho guanine nucleotide exchange factor 11 (ARHGEF11) functions as an activator of Rho GTPases and is thought to influence insulin signaling.
4774 21130749 Likewise, dysregulation of the fuel-sensing enzyme AMP-activated protein kinase (AMPK) has been proposed as a pathogenetic factor for these abnormalities based on both its links to insulin action and its anti-inflammatory effects.
4775 21249158 In an independent experiment, insulin replacement therapy normalized the expression of some proteins (Dbi, Anxa5) while other proteins (Cp, Cryba3, Lgals3, Stat3) were only partially normalized and Fgf2 and Crybb2 expression remained elevated.
4776 20434290 Insulin use was associated with greater improvements in SBP and DBP.
4777 19350199 Compared with insulin treatment, APS treatment significantly reduced myocardial collagen (type I and III) expression and lowered cardiac MMP-2 activity, myocardial Ang II levels, myocardial chymase expression, and p-ERK1/2 kinase expression.
4778 19350199 In diabetic hamsters, myocardial ACE expression and plasma Ang II levels was not altered by insulin or APS treatment.
4779 19876588 These data show that caloric restriction notably improves the sensitivity to insulin and significantly increases mRNA and protein expression of SIRT1 while decreasing the apoptosis ratio of islet beta cells in diabetic rats.
4780 20153489 Furthermore, changes in plasma leptin (r = -0.432, P < .001) and leptin mRNA (r = -0.298, P = .019) correlated significantly with changes in insulin sensitivity.
4781 20153489 This work shows that exercise training has differing effects on leptin-related variables between women with and without a diabetes family history and suggests that these molecular differences may contribute to the differential effects of exercise training on insulin sensitivity between these 2 groups.
4782 20695765 The adipokine, leptin, regulates blood glucose and the insulin secretory function of beta cells, while also modulating immune cell function.
4783 20979575 In conclusion, obesity alone or obesity associated with Type 2 diabetes alters human periumbilical adipose tissue arterioles in terms of structure, function and biochemsitry, including diminished eNOS expression and reduced levels of IRS-1, IRS-2, PI3K and Akt in the insulin signalling pathway.
4784 21051417 This review focuses on insulin-initiated PI3K-Akt-eNOS survival signalling, with nitric oxide as an 'end effector' delivering cardioprotection in health and disease (especially in ischaemic heart disease), and highlights the impairment of this survival signalling as a key link between insulin resistance and cardiovascular disease.
4785 21139073 Since plasma DPP4 activity demonstrated significant positive correlations with body weight and the fasting plasma insulin level but not with the fasting blood glucose level during the late stage of diabetes, body fat and fasting plasma insulin levels may be useful factors for predicting the control of plasma DPP4 activity.
4786 21143620 These beneficial effects of metformin were associated with increased AMPK and eNOS phosphorylation, as well as reductions in insulin, TGF-?1, basic fibroblast growth factor and tumour necrosis factor-? levels in the circulation and/or myocardium. 4.
4787 21270254 We previously showed that a high-calorie diet and insulin induce Foxc2 in adipocytes; the current findings identify a previously unknown role for Foxc2 as an important metabo-regulator of mitochondrial morphology and metabolism.
4788 21270258 Phosphatidylinositol-4-phosphate-5-kinase (PI4P5K) has been proposed to facilitate regulated exocytosis and specifically insulin secretion by generating phosphatidylinositol-4,5-bisphosphate (PIP(2)).
4789 21270259 Transforming growth factor-?/Smad3 signaling has been implicated in various metabolic processes, including adipogenesis, insulin expression, and pancreatic ?-cell function.
4790 21270259 Smad3-knockout mice exhibited diminished adiposity with improved glucose tolerance and insulin sensitivity.
4791 21270264 In addition, using both MIN-6 cells, a murine ?-cell line, and pancreatic islets isolated from mice, we analyzed the in vitro effects of IL-6 pretreatment on insulin secretion.
4792 21270264 Furthermore, using pharmacological inhibitors and small interfering RNAs, we studied the intracellular signaling pathway through which IL-6 may affect insulin secretion from MIN-6 cells.
4793 21270265 GIP is an incretin, known to modulate glucose-induced insulin secretion.
4794 21270265 Here we studied the role of GIP signaling in insulin-positive differentiation in the embryonic mouse pancreas.
4795 21270265 Morpholine-ring antisense or siRNA against either GIP ligand or GIP receptor both inhibited the differentiation of insulin-positive cells.
4796 21270265 GIP signaling may play a role in early embryonic pancreas differentiation to form insulin-positive cells or ?-cells.
4797 21270272 Although U0126, an ERK inhibitor, enhanced insulin sensitivity and attenuated oxidative stress-induced insulin resistance, LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), worsened the insulin resistance.
4798 21270272 Moreover, insulin increased Nrf2 transcriptional activity, which was blocked by LY294002 but enhanced by U0126.
4799 21270272 Forced activation of Nrf2 by adenoviral over-expression of Nrf2 inhibited the increased ERK activity and recovered the blunted insulin sensitivity on glucose uptake in cardiomyocytes that were chronically treated with H(2)O(2).
4800 21270272 ERK-mediated suppression of Nrf2 activity leads to the oxidative stress-induced insulin resistance in adult cardiomyocytes and downregulated glucose utilization in the diabetic heart.
4801 21274399 The aim of this study was to investigate whether insulin deficiency and increased catabolism may have a role in the regulation of plasma glucagon-like peptide (GLP)-1 and GLP-2 levels in children with diabetic ketoacidosis (DKA) and whether insulin treatment may affect the levels of these polypeptides.
4802 20698813 Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that potentiates nutrient-induced insulin release.
4803 20829805 The ?(2)-adrenergic receptor (ADRB2) mediates obesity, cardiorespiratory fitness, and insulin resistance.
4804 20829805 We examined the hypothesis that ADRB2 Arg16Gly-Gln27Glu haplotype is associated with body composition, glucose tolerance, and insulin sensitivity in obese, postmenopausal women.
4805 20829805 We found that ADRB2 haplotype was independently associated with % body fat, abdominal fat distribution, VO(2(max)), insulin sensitivity (M/?Insulin), and glucose tolerance (ANOVA, P < 0.05 for all).
4806 21050716 Blood CD4(+) cells stimulated to divide in response to GAD65 (in three healthy individuals) or proinsulin (in one type 1 diabetic) were flow sorted into single cells and cultured on feeder cells in the presence of anti-CD3 monoclonal antibody, IL-2 and IL-4.
4807 21122860 PCSK9 mRNA expression may be upregulated by insulin in murine models.
4808 21122860 Individual absolute and relative changes in LDL cholesterol, apolipoprotein B and triglycerides after 24h of insulin were unrelated to changes in PCSK9 (P > 0.15 for all).
4809 21159034 To investigate changes in maternal serum resistin levels during pregnancy and postpartum and clarify their relationship to insulin resistance.
4810 19737522 They maintain insulin sensitivity in liver and fat, without activation of the proinflammatory JNK pathway.
4811 20504094 Compared to the controls, the GDM group had significantly higher mean values for serum glucose, insulin, HOMA-IR, triglyceride, GGT and plasma PAF-AH activity, and a statistically higher prevalence of MS.
4812 20980260 STAT1, but not IRF-1, mediates the cytokine-induced loss of the differentiated ?-cell phenotype, as indicated by decreased insulin, Pdx1, MafA, and Glut2.
4813 21102330 ApoA-I and HDL stimulate insulin secretion by interaction with ABCA1, ABCG1 or SR-BI and also inhibit apoptosis of ?-cells.
4814 18984671 TRIB3 inhibits insulin-stimulated Akt phosphorylation and subsequent insulin action.
4815 21098489 Here, we demonstrate that de novo lipogenesis, an insulin-dependent process driven by the multifunctional enzyme fatty-acid synthase (FAS), maintains endothelial function by targeting endothelial nitric-oxide synthase (eNOS) to the plasma membrane.
4816 21098489 Insulin induced FAS in endothelial cells freshly isolated from humans, and eNOS palmitoylation was decreased in mice with insulin-deficient or insulin-resistant diabetes.
4817 21299122 Protein tyrosine phosphatase 1beta (PTP1beta) acts as a negative regulator of insulin signaling.
4818 15895078 The insulin/IGF-1 (insulin-like growth factor 1) signalling pathway promotes adipocyte differentiation via complex signalling networks.
4819 20144759 Here, we provide evidence that double-stranded RNA-dependent protein kinase (PKR) can respond to nutrient signals as well as endoplasmic reticulum (ER) stress and coordinate the activity of other critical inflammatory kinases such as the c-Jun N-terminal kinase (JNK) to regulate insulin action and metabolism.
4820 20393858 In pancreatic islets isolated from Trpm5 (-/-) -mice, hyperglycemia as well as arginine-induced insulin secretion was diminished.
4821 20844837 Therefore, we hypothesized that sex hormones affect the expression of caveolin-1 and contribute to the development of insulin resistance and hyperglycemia in JYD mice.
4822 20844837 Orchidectomized JYD male mice showed improved glucose and insulin tolerance with a concomitant increase in the expression of insulin-signaling molecules and caveolin-1 in adipose tissue and skeletal muscle.
4823 19237574 In addition, we found that glucose deprivation and various tyrphostins, known inhibitors of insulin-like growth factors/insulin receptor tyrosine kinases, do not modulate the effect of metformin on Abeta.
4824 20439437 Our aims were to determine whether sEH is involved in the regulation of hyperglycemia in diabetic mice and to investigate the reasons for the regulation of insulin secretion by sEH deletion or inhibition in islets.
4825 20439437 We also examined the effects of sEH KO or t-AUCB on glucose-stimulated insulin secretion (GSIS) and intracellular calcium levels in islets.
4826 20439437 More important, when insulin levels were assessed by hyperglycemic clamp study, sEH KO was found to promote insulin secretion.
4827 21094196 Ghrelin can inhibit gluco/lipotoxicity induced insulin resistance by PI3K/AKT pathway.
4828 21099327 Activation of mouse ?-cell CB1 and CB2 receptors resulted in decreased cyclic AMP, increased calcium and potentiation of glucose-stimulated insulin secretion.
4829 21129425 The results of histopathological and immunohistochemical analysis showed that VIP and the VPAC1 agonist improved the structure and cellularity of islets and ameliorated the insulin-secreting activity of islets.
4830 21159853 Instead, leptin action in the brain potently suppresses hepatic glucose production while increasing tissue glucose uptake despite persistent, severe insulin deficiency.
4831 21159853 This leptin action is distinct from its previously reported effect to increase insulin sensitivity in the liver and offers compelling evidence that the brain has the capacity to normalize diabetic hyperglycemia in the presence of sufficient amounts of central nervous system leptin.
4832 21189286 To elucidate the mechanism of how insulin signaling induces RDS, bronchoalveolar epithelium-specific Akt1 transgenic (TG) mice were generated.
4833 21189286 In cultured lung epithelial cells, insulin reduced VEGF expression and transcriptional activity of HIF-2 on VEGF promoter in an mTOR-dependent manner.
4834 21251282 Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis.
4835 19571229 Knockout mice that lack gustducin or the sweet taste receptor subunit T1r3 have deficiencies in secretion of glucagon-like peptide 1 and glucose-dependent insulinotropic peptide and in the regulation of plasma concentrations of insulin and glucose in response to orally ingested carbohydrate-ie, their incretin effect is dysfunctional.
4836 20798476 Retinol-binding protein 4 (RBP4), one of the new adipocytokine, is recently reported to provide a link between insulin resistance and features of metabolic factors.
4837 20827659 The critical role of pdx-1 in stimulating certain endocrine pancreatic properties in RSCs was further confirmed upon the introduction of an expression construct for pdx-1 which markedly induced insulin and somatostatin.
4838 20827661 Moreover, serum resistin was not influenced by insulin resistance in either group examined.
4839 20946008 Fetuin-A has been associated with insulin resistance and inversely related with vascular calcification.
4840 20946008 Serum fetuin-A concentration was not associated with measures of insulin resistance or with preclinical atherosclerosis in Hispanics and NHW.
4841 21031343 Vaspin, adiponectin and interleukin-6 (IL-6) constitute novel adipose-tissue derivatives, known as adipokines, which mediate insulin resistance.
4842 21031343 Both rosiglitazone/metformin combination therapy and metformin monotherapy decreased serum vaspin levels through glucose and insulin sensitivity regulation, while they exerted differential effects on adiponectin, IL-6 and other cardiovascular risk factors in drug-naļve patients with T2DM.
4843 21104585 The lipocalins retinol-binding protein (RBP)-4, lipocalin-2 and lipocalin-type prostaglandin D-synthase (L-PGDS) have been suggested to mediate obesity-associated insulin resistance and other metabolic co-morbidities.
4844 21104585 ?These results suggest that RBP-4, lipocalin-2 and L-PGDS do not regulate insulin sensitivity in healthy men.
4845 21177830 The vasodilator ?-blocker nebivolol reduces nicotinamide adenine dinucleotide phosphate oxidase activity, increases bioavailable nitric oxide, and improves insulin sensitivity.
4846 21177830 Compared with Zucker lean, ZO controls exhibited increased proteinuria and ?-glutamyl transpeptidase, reductions in systemic insulin sensitivity in association with increased renal renin, (pro)renin receptor, angiotensin II type 1 receptor, and mineralocorticoid receptor immunostaining, oxidative stress, and glomerular tubular structural abnormalities that were substantially improved with in vivo nebivolol treatment.
4847 18773087 Only when the parenchymal elements lacked JNK1 could we demonstrate a significant increase in systemic insulin sensitivity.
4848 20199782 Therefore, the maintenance of low levels of circulating fetuin-A may be a novel mechanism contributing to enhanced insulin sensitivity with regular physical activity.
4849 21095180 Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic ? cells.
4850 21134353 In conclusion, CR reduced ER stress and improved hepatic insulin action by suppressing JNK-mediated IRS-1 serine-phosphorylation in ob/ob mice.
4851 21219897 With increasing quartiles of visceral fat, there was a significant increase in insulin resistance (p=0.040); significant decrease in adiponectin (p=0.043) and increase in TNF-alpha (p=0.028), hs-CRP (p=0.043), OX-LDL (p=0.034) and visfatin (p=0.040), and carotid IMT (p=0.047) was observed.
4852 21318185 BrdU incorporation by beta cells, islet size, and circulating insulin levels were significantly increased in Men1-excised mice.
4853 18046409 SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity.
4854 18046409 Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival.
4855 18046409 In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver.
4856 20107110 Sirtuin 1 (SIRT1) is implicated in the regulation of mitochondrial function, energy metabolism, and insulin sensitivity in rodents.
4857 20107110 No studies are available in humans to demonstrate that SIRT1 expression in insulin-sensitive tissues is associated with energy expenditure and insulin sensitivity.
4858 20107110 Adipose tissue SIRT1 mRNA expression was significantly associated with EE (r = 0.289, P = 0.010) and with insulin sensitivity (r = 0.334, P = 0.002) during hyperinsulinemic-euglycemic clamp.
4859 20107110 Impaired stimulation of EE by insulin and low SIRT1 expression in insulin-sensitive tissues is likely to reflect impaired regulation of mitochondrial function associated with insulin resistance in humans.
4860 20603627 However, FABP4 knockdown did not affect plasma glucose and lipid homeostasis in DIO mice; nor did it improve their insulin sensitivity.
4861 21263211 Paired-homeodomain transcription factor 4 (PAX4) functions as a transcriptional repressor and is involved in the differentiation of insulin-secreting ?-cells.
4862 20031167 Expression of cyclin A2, cyclin B1, TERT mRNA, and telomerase activity were decreased in insulin-deficient rats.
4863 20031167 Increased Bax, Daxx, and JNK mRNA expression and decreased Bcl X(L) expression in insulin-deficient rats, led to increased hepatocyte apoptosis than normal rats.
4864 20089385 Insulin is responsible for proteosynthesis control through IRS/AKT/P70S6k/PHAS1 pathways modulation, glucose homeostasis through PKC/Flotillin-2/caveolin-3/Cbl activation and muscle differentiation/hypertrophy via muscle-specific MHC gene transcription control.
4865 20089385 We demonstrated that insulin or conglutin-? cell stimulation resulted in the persistent activation of protein synthetic pathway kinases and increased glucose transport, glut4 translocation and muscle-specific gene transcription regulation.
4866 20089385 Our results indicate that conglutin-? may regulate muscle energy metabolism, protein synthesis and MHC gene transcription through the modulation of the same insulin signalling pathway, suggesting the potential therapeutic use of this natural legume protein in the treatment of diabetes and other insulin-resistant conditions, as well as the potential conglutin-? influence on muscle cells differentiation and regulation of muscle growth.
4867 20215576 These results demonstrate that CaMKII does not regulate insulin-stimulated glucose uptake in skeletal muscle.
4868 20501596 Bone-derived undercarboxylated osteocalcin regulates insulin secretion and sensitivity in mice, and reduced serum total osteocalcin (TOC) is associated with diabetes in humans.
4869 20797821 Butyrylcholinesterase may have a role in a number of metabolic functions and could affect the expression of insulin resistance syndrome.
4870 20886041 Dispersed human pancreatic islets and MIN6 beta-cells were infected with a dual reporter lentivirus containing both eGFP driven by the insulin promoter and mRFP driven by the pdx1 promoter.
4871 20886041 Using this approach and 5 replicate screens, we identified 7 extracts that reproducibly changed insulin and/or pdx1 promoter activity from a library of 1319 marine invertebrate extracts.
4872 21215314 Following chronic administration to db/db mice, EGT1442 dose-dependently reduced HbA(1c) and blood glucose concentration without affecting body mass or insulin level.
4873 21217695 We show that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity.
4874 21217695 Ablation of Nlrp3 in mice prevents obesity-induced inflammasome activation in fat depots and liver as well as enhances insulin signaling.
4875 21217695 Collectively, these data establish that the Nlrp3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.
4876 20579864 Adipocyte-specific fatty acid-binding protein (A-FABP) is a cytoplasmic protein that is expressed in adipocytes and is closely associated with insulin resistance, metabolic syndrome, and Type 2 diabetes.
4877 21115020 Such fibers are thought to improve glycemic control through increased GLP-1 induced insulin secretion.
4878 21115020 PGX® improved glycemic control and reduced protein glycation, most likely due to the insulin secretagogue effects of increased GLP-1.
4879 21143769 All three dose levels dose dependently resulted in decreases in glycated hemoglobin, serum glucose, and nitric oxide, with concomitant increases in serum insulin levels.
4880 21147013 Conversely, G6PD deficiency can promote oxidative stress and impairment of insulin secretion by beta cells.
4881 21219913 Our goal was to test the hypothesis that the histidine-induced activation of calcium sensing receptor (CaR) can regulate calcium channel activity of L-type voltage dependent calcium channel (VDCC) due to increased spatial interaction between CaR and VDCC in ?-cells and thus modulate glucose-induced insulin secretion.
4882 21241662 Phosphorylation of p38 MAPK Thr180/Tyr182 was transiently increased by H2O2 in the presence and absence of insulin at 2 and 4 h, but not at 6 h.
4883 21241662 Selective inhibition of p38 MAPK with A304000 partially rescued the H2O2-induced reduction in insulin-stimulated glucose transport activity.
4884 21241662 These results indicate that direct in vitro exposure of isolated mammalian skeletal muscle to a low-level oxidant stress impairs distal insulin signaling and insulin-stimulated glucose transport activity, at least in part, due to a p38 MAPK-dependent mechanism.
4885 14342522 The results indicate that insulin acts by increasing glucose utilization, and not by exerting a direct effect on citrate-cleavage enzyme or acetate thiokinase.
4886 17575082 Compared with control blastocysts, blastocysts exposed to high concentrations of IGF-I showed a decrease in AMPK activation and insulin-stimulated glucose uptake and an increase in the number of apoptotic nuclei.
4887 19032932 Therefore, expression and/or function of SMIT2, a high affinity transporter specific for DCI and myo-inositol, may be reduced in diabetes mellitus, insulin resistance and polycystic ovary syndrome causing the abnormal DCI metabolism observed in these conditions.
4888 19509018 In this study, we determined whether Mstn disruption could prevent the development of insulin resistance, proatherogenic dyslipidemia, and atherogenesis.
4889 19509018 The effects of high-fat/high-cholesterol diet on body composition, plasma lipids, systemic and tissue-specific insulin sensitivity, hepatic steatosis, as well as aortic atheromatous lesion were characterized in Mstn(-/-)/Ldlr(-/-) mice in comparison with control Mstn(+/+)/Ldlr(-/-) mice.
4890 19509018 Compared with Mstn(+/+)/Ldlr(-/-) controls, Mstn(-/-)/ Ldlr(-/-) mice were resistant to diet-induced obesity, and had greatly improved insulin sensitivity, as indicated by 42% higher glucose infusion rate and 90% greater muscle [(3)H]-2-deoxyglucose uptake during hyperinsulinemic-euglycemic clamp.
4891 19509018 Inactivation of Mstn protects against the development of insulin resistance, proatherogenic dyslipidemia, and aortic atherogenesis in Ldlr(-/-) mice.
4892 19667238 In addition, 1,25(OH)(2)D(3) suppression of macrophage endoplasmic reticulum stress improved insulin signaling, downregulated SR-A1 expression, and prevented oxidized and acetylated low-density lipoprotein-derived cholesterol uptake.
4893 20949640 In addition, LPS stimulation impaired the glucose-mediated insulin secretion in rat islets. ?-GalCer and sulfatide, glycolipids that are related to insulin processing and secretion, are possibly interacting with the CD14 receptor complex. ?-GalCer had an LPS-like, serum- and CD14-dependent effect on the induction of pro-inflammatory cytokines in a human monocyte cell line.
4894 21153603 Exogenous insulin therapy improves endothelial function in insulin resistant patients, indirectly indicating that nitric oxide synthase activity and NO production may be impaired.
4895 21153603 This study investigated whether elevated Angiotensin II influences myocardial insulin resistance, insulin signaling and NO production in a rat model of diet-induced obesity (DIO) by antagonizing the actions of the AT1 receptor with Losartan.
4896 21153603 We conclude that Angiotensin II signaling exacerbates inhibition of NO production in insulin resistance and that this can be improved by AT1 antagonism.
4897 21239445 Nox4 knockdown, which is reportedly to produce ROS in insulin signaling, attenuated IGF-I-induced IGF-IR phosphorylation, indicating that Nox4 is involved in the regulation of IGF-I signaling.
4898 16444902 Insulin and IGF-I may modulate brain levels of insulin degrading enzyme, which would also lead to an accumulation of Abeta amyloid.
4899 19996311 However, the regulation of REDD1 expression in response to insulin remains unknown.
4900 19996311 In the present study, we demonstrate that in murine and in human adipocytes, insulin stimulates REDD1 expression.
4901 19996311 Moreover, using echinomycin, a hypoxia-inducible factor 1 (HIF-1) inhibitor, and HIF-1alpha small interfering RNA, we demonstrate that insulin stimulates REDD1 expression only through the transcription factor HIF-1.
4902 19996311 In conclusion, our study shows that insulin stimulates REDD1 expression in adipocytes.
4903 20022950 To explore the mechanism of insulin resistance, we have developed a novel system to activate Akt independently of its upstream effectors as well as other insulin-responsive pathways such as mitogen-activated protein kinase. 3T3-L1 adipocytes were rendered insulin-resistant either with chronic insulin or dexamethasone treatment, but conditional activation of Akt2 stimulated hemagglutinin-tagged glucose transporter 4 translocation to the same extent in these insulin-resistant and control cells.
4904 20829802 Chemical chaperone tauroursodeoxycholic acid (TUDCA) can reduce FFA-induced adipocyte inflammation and improve insulin signaling whereas overexpression of spliced X-box protein 1 (XBP-1s) only attenuates FFA-induced inflammation.
4905 20829802 Deficiency of PERK attenuates FFA-induced activation of IKK? and deficiency of IKK? alleviates FFA-induced inflammation and insulin resistance.
4906 21241768 In muscle cells and HEK293 cells, downregulation of SIRT1 reduced, while overexpression increased, insulin-induced PKB activatory phosphorylation.
4907 21241768 Our data identify SIRT1 as a positive modulator of insulin signaling in muscle cells through PI3K, and this mechanism appears to be conserved from C. elegans through humans.
4908 21186369 The adipocyte-derived secretory factor adiponectin promotes insulin sensitivity, decreases inflammation and promotes cell survival.
4909 21239612 Insulin-induced intracellular signaling, activation of stress (c-Jun N-terminal kinase) signaling, and glucose metabolism were all normalized by superoxide dismutase 2 overexpression or by pretreatment with antioxidants.
4910 21244702 The link between glucocorticoids and insulin resistance may involve the adiponectin receptors and adrenalectomy might play a role not only in regulate expression and secretion of adiponectin, as well regulate the respective receptors in several tissues.
4911 20731625 No effect was observed on Akt and ERK1/2 phosphorylation. (1) Physiological FFA elevations require at least 120 min to induce insulin resistance, (2) that insulin resistance peaks 360 min after initiation of FFA exposure and (3) ceases 210 min after termination of the FFA infusion.
4912 21163363 Misfolded human islet amyloid polypeptide (hIAPP) in pancreatic islets is associated with the loss of insulin-secreting beta cells in type 2 diabetes.
4913 21185935 These data indicate that exercise training can attenuate oxidative stress and increase mitochondrial DNA content in skeletal muscle in rats with T2DM and that exercise-induced suppression of p53 and TIGAR expression may play a role in preventing oxidative stress in insulin resistance.
4914 21252113 Furthermore, troxerutin significantly inhibited the activation of c-jun N-terminal kinase 1 and I?B kinase ?/nuclear factor-?B induced by endoplasmic reticulum stress and enhanced insulin signalling pathway, which prevented obesity, restored normal levels of blood glucose, fatty acids and cholesterol and increased the phosphorylation of cyclic adenosine monophosphate response element-binding protein and the expression levels of c-fos in the hippocampus.
4915 20577883 GEB-H, mainly as a result of the action of 4-hydroxybenzaldehyde and vanillin, reduces insulin resistance by decreasing fat accumulation in adipocytes by activating fat oxidation and potentiating leptin signaling in diet-induced obese rats.
4916 10909973 Glucagon-like peptide 1 (GLP-1), a hormonal activator of adenyl cyclase, stimulates insulin gene transcription, an effect mediated by the cAMP response element (CRE) of the rat insulin I gene promoter (RIP1).
4917 20032470 SCD knockdown with small interfering RNA caused down-regulation of DNL and of expression of DNL-related genes, with reduced membrane fluidity (p < 0.02) and insulin sensitivity (p < 0.01), compared with scrambled small interfering RNA controls.
4918 20888730 DC260126 could significantly decrease serum insulin levels, improve insulin tolerance and increase Akt phosphorylation levels in liver, suggesting improved insulin sensitivity in DC260126-treated rats.
4919 19761474 Reduced circulating adiponectin levels contribute to the aetiology of insulin resistance.
4920 19761474 The genetic control of HMW adiponectin is shared in part with insulin resistance-related traits and involves, but is not limited to, the ADIPOQ locus.
4921 19959757 Ceramide is now recognized as a negative regulator of insulin signaling by impairing protein kinase B (PKB)/Akt activation.
4922 19959757 We have used different PKCzeta mutant constructs or the PP2A inhibitor, okadaic acid (OKA), to selectively inhibit PKCzeta- and PP2A-dependent pathways in cells expressing different caveolin-1 levels and evaluated the impact of insulin and ceramide on PKB/Akt activity in different PM subdomains.
4923 19996381 The mammalian silent information regulator 2 homolog SIRT1 modulates several physiological processes important for life span, and a potential role of SIRT1 in the regulation of insulin sensitivity has been shown.
4924 19996381 In conclusion, these results define a novel role for SIRT1 as an important regulator of macrophage inflammatory responses in the context of insulin resistance and raise the possibility that targeting of SIRT1 might be a useful strategy for treating the inflammatory component of metabolic diseases.
4925 19996382 Tribbles homolog 3 (TRIB3) was found to inhibit insulin-stimulated Akt phosphorylation and modulate gluconeogenesis in rodent liver.
4926 19996382 We found that 1) skeletal muscle TRIB3 protein levels are significantly elevated in T2DM patients; 2) muscle TRIB3 protein content is inversely correlated with glucose disposal rates and positively correlated with fasting glucose; 3) skeletal muscle TRIB3 protein levels are increased in STZ-diabetic rats, db/db mice, and Zucker fatty rats; 4) stable TRIB3 hyperexpression in muscle cells blocks insulin-stimulated glucose transport and glucose transporter 4 (GLUT4) translocation and impairs phosphorylation of Akt, ERK, and insulin receptor substrate-1 in insulin signal transduction; and 5) TRIB3 mRNA and protein levels are increased by high glucose concentrations, as well as by glucose deprivation in muscle cells.
4927 19996382 These data identify TRIB3 induction as a novel molecular mechanism in human insulin resistance and diabetes.
4928 19996382 TRIB3 acts as a nutrient sensor and could mediate the component of insulin resistance attributable to hyperglycemia (i.e., glucose toxicity) in diabetes.
4929 20009098 RESEARCH DESIGN AND METHODS The associations between ucOC, cOC, total and high-molecular-weight (HMW) adiponectin, and insulin secretion (homeostasis model assessment [HOMA]-beta) were investigated in a population-based sample of healthy prepubertal children (n = 103; 49 boys and 54 girls).
4930 20028942 To define the relationship between these two signaling pathways in the regulation of liver metabolism, we used genetic and pharmacological approaches to study the effects of inhibiting PTP1B on hepatic insulin signaling and expression of gluconeogenic enzymes in IRS2(-/-) mice.
4931 20028942 Additionally, hepatic insulin signaling was assessed in control and IRS2(-/-) mice treated with resveratrol, an antioxidant present in red wine.
4932 20028942 By regulating the phosphorylation state of IR, PTB1B determines sensitivity to insulin in liver and exerts a unique role in the interplay between IRS1 and IRS2 in the modulation of hepatic insulin action.
4933 20092903 To examine whether the GLP-1 agonist exenatide or the inhibitor of the GLP-1-degrading enzyme dipeptidyl peptidase 4 (DPP-4) sitagliptin rescue insulin gene expression in rats infused for 72h with glucose+Intralipid, independently from their glucose-lowering action.
4934 20092903 Neither a GLP-1 agonist nor a DPP-4 inhibitor, at doses that do not alter blood glucose levels, prevented the inhibition of insulin gene expression in this in vivo model of glucolipotoxicity.
4935 20097709 Insulin (5-10 nm) suppressed all TCF7L2 isoforms in SGBS cells but suppressed exon 13a-containing isoforms most significantly (P < 0.001).
4936 15331531 Insulin-stimulated glucose uptake in skeletal muscle was increased by twofold in Syn4 transgenic mice compared with wild-type mice as assessed by hyperinsulinemic-euglycemic clamp analysis, consistent with a twofold increase in insulin-stimulated GLUT4 translocation in skeletal muscle.
4937 15331531 In sum, these data suggest that increasing the number of Syn4-Munc18c "fusion sites" at the plasma membrane of skeletal muscle increases the amount of GLUT4 available to increase the overall rate of insulin-mediated glucose uptake in vivo.
4938 15734838 The disruption of Munc18c binding to syntaxin 4 impairs insulin-stimulated GLUT4 vesicle translocation in 3T3L1 adipocytes.
4939 16638745 Tyrosine phosphorylation of Munc18c was also detected in 3T3L1 adipocytes and increased with insulin stimulation, suggesting that this may be a conserved mechanism.
4940 18285343 Disruption of F-actin-Syntaxin 4 binding correlated with enhanced glucose-stimulated insulin secretion, mediated by increased granule accumulation at the plasma membrane and increased Syntaxin 4 accessibility under basal conditions.
4941 19883376 Brd2 is highly expressed in pancreatic beta-cells, where it normally inhibits beta-cell mitosis and insulin transcription.
4942 21190012 Important glucose-responsive transcription factors, Mafa and Pdx1, regulate genes involved in insulin synthesis and secretion, and have been implicated in late beta cell development.
4943 21190012 After infection with adenovirus expressing MAFA, Pdx1 or green fluorescent protein (Gfp), P2 rat islets were evaluated by RT-PCR and insulin secretion with static incubation and reverse haemolytic plaque assay (RHPA).
4944 21190012 Overexpression of Pdx1 increased Mafa, Neurod1, glucokinase (Gck) mRNA and insulin content but failed to enhance glucose responsiveness.
4945 21190012 Similar overexpression of MAFA resulted in increased Neurod1, Nkx6-1, Gck and Glp1r mRNAs and no change in insulin content but, importantly, acquisition of glucose-responsive insulin secretion.
4946 21319195 The rs738409 C>G patatin-like phospholipase domain-containing 3 (PNPLA3) single nucleotide polymorphism (SNP), encoding for the I148M protein variant, influences liver fat without affecting insulin resistance and body composition.
4947 21336277 Inactivation of the INS promoter by promoter-targeting siRNA reduces SYT8 gene expression.
4948 21336277 These results reveal a nonredundant role for SYT8 in insulin secretion and indicate that the INS promoter acts from a distance to stimulate SYT8 transcription.
4949 21358697 Consequently, SGLT2 inhibitors reduce plasma glucose insulin independently and improve insulin resistance in diabetes.
4950 21358698 Animal studies suggest that reduction of hyperglycemia with SGLT2 inhibitors may also improve insulin sensitivity and preserve ?-cell function.
4951 17971451 Basal but not insulin-stimulated glucose uptake is elevated in isolated soleus muscle from Hfe(-/-) mice (p < 0.03).
4952 17971451 Compared with controls Hfe(-/-) mice exhibit no differences in serum lipid, insulin, glucagon, or thyroid hormone levels; adiponectin levels are elevated 41% (p < 0.05), and the adiponectin message in adipocytes is increased 83% (p = 0.04).
4953 17971451 Insulin action measured by phosphorylation of Akt is not enhanced in muscle, but phosphorylation of AMP-dependent kinase is increased.
4954 20299468 To explore whether the disparate glucagon responses seen were in part due to changes in ventromedial hypothalamus (VMH) exposure to insulin, bilateral guide cannulas were inserted to the level of the VMH and 8 days later rats received a VMH microinjection of either 1) anti-insulin affibody, 2) control affibody, 3) artificial extracellular fluid, 4) insulin (50 microU), 5) insulin receptor antagonist (S961), or 6) anti-insulin affibody plus a gamma-aminobutyric acid A (GABA(A)) receptor agonist muscimol, prior to a hypoglycemic clamp or under baseline conditions.
4955 20820848 Inhibiting DGAT or CPT-1 by using, respectively, amidepsine or etomoxir increased DAG accumulation and sensitized myotubes to palmitate-induced insulin resistance.
4956 20807725 The regulation of insulin exocytosis in rodent ?-cells and responsiveness to incretins are reliant on Rab family members, notably Rab3a and Rab27a, but not Rab3b.
4957 21090814 This approach was used to screen both the c-Jun N-terminal protein kinase Jnk-1 (involved in insulin signaling) and p38? (involved in the formation of TNF? and other cytokines).
4958 21090814 Medicinal chemistry studies resulted in an improved Jnk-1 ligand able to increase adiponectin secretion in human adipocytes and increase insulin-induced protein kinase PKB phosphorylation in human hepatocytes, in similar fashion to Jnk-1 siRNA and to rosiglitazone treatment.
4959 21107520 Plasma glucose, plasma insulin and total pancreatic insulin were determined, and forkhead box O1 protein (FOXO1) phosphorylation and the transcription factors pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 protein (NKX6.1) and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (avian) (MAFA) were monitored by immunohistochemistry for 16 days.
4960 21107520 Hyperglycaemia caused a dramatic dephosphorylation of FOXO1 at day 2, followed by a progressive depletion of insulin stores.
4961 21185820 APOC3 -482TT genotype is associated with high apoC-III concentrations only in the presence of abdominal obesity or insulin resistance, but not in current smokers who remain lean or insulin-sensitive.
4962 21212741 As mis-regulated insulin signaling in peripheral tissues is known to cause similar phenotypes, our data suggest a role for Drosophila IDE in determining the level of insulin-like peptides made by IPCs that systemically activate insulin signaling.
4963 21256171 Preclinical and clinical studies suggest that whey proteins can reduce postprandial glucose levels and stimulate insulin release in healthy subjects and in subjects with type 2 diabetes by reducing dipeptidyl peptidase-4 (DPP-4) activity in the proximal bowel and hence increasing intact incretin levels.
4964 21321316 In conclusion, KTD impairs energy and glucose homeostasis by exacerbating insulin resistance and attenuating hypothalamic leptin signaling in non-obese type 2 diabetic rats.
4965 15517149 Our results add to growing evidence that resistin is associated with variation in weight, fat distribution and insulin resistance.
4966 20085539 Although insulin-induced phosphorylation of IRS (insulin receptor substrate) and Akt remained intact in glycosphingolipid-depleted cells, both in vitro budding of GLUT4 vesicles and FRAP of GLUT4-GFP on GSVs were stimulated.
4967 20085539 Glycosphingolipid depletion also enhanced the insulin-induced translocation of VAMP2 (vesicle-associated membrane protein 2), but not the transferrin receptor or cellubrevin, indicating that the effect of glycosphingolipids was specific to VAMP2-positive GSVs.
4968 21047927 We aimed to determine the impact of insulin resistance and reduced glucose tolerance on postprandial GIP, GLP-1, and glucagon responses in healthy subjects.
4969 21084403 Insulin did not change CRP [4.5 (2.1-11.7) vs. 6.8 (2.4-10.3), P = 0.35], soluble CD40 ligand [402 (191-843) vs. 610 (230-1200), P = 0.68], IL-6 [6.21 (3.1.-10.4) vs. 10.37 (5.9-15.3), P = 0.09], and ET-1 [1.02 (0.7-1.8) vs. 1.10 (0.7-1.9), P = 0.657].
4970 21216462 Impairments in leptin-melanocortin signaling are associated with insulin-deficient diabetes and leptin treatment has been shown to be effective in reversing hyperglycemia in animal models of type 1 diabetes.
4971 21216462 MTII treatment also significantly reduced expression levels of hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) mRNA in white adipose tissue of diabetic mice without a significant change in serum insulin levels.
4972 21263116 Interestingly, the sympathetic response to insulin was eliminated by PVN injection of the melanocortin 3/4 receptor antagonist SHU9119, but was unaffected by the angiotensin II type 1 receptor antagonist losartan.
4973 20424419 Chemerin was recently introduced as a novel adipokine playing a crucial role in adipocyte differentiation and insulin signaling.
4974 18220632 Increased expression of UCP3 in skeletal muscle is associated with protection from diet-induced insulin resistance in mice.
4975 18723371 The proinflammatory cytokine Interleukin 1 beta (IL-1beta) is elevated in obese individuals and rodents and it is implicated in impaired insulin secretion, decreased cell proliferation and apoptosis of pancreatic beta cells.
4976 20380650 JTT-551, a newly developed PTP1B inhibitor, improves glucose metabolism by enhancement of insulin signalling and could be useful in the treatment of type 2 diabetes mellitus.
4977 21123956 Effects of ATR on the insulin resistance of age-matched (13-week-old) and unoperated KK/Ay mice were assessed by the glucose tolerance test, circulating adiponectin concentration, and changes in insulin signaling (IRS-1/Akt phosphorylation).
4978 21414238 The plasma activities and antigens of PAI-1 and tPA and the levels of the tPA/PAI-1 complex as well as serum insulin, parameter of the coronary risk panel and plasma glucose at fasting state were studied in 303 T2D subjects (227 with MetS and 76 without MetS), 131 normal non-diabetic non-metabolic subjects and 101 non-diabetic MetS subjects.
4979 21437074 This increases circulating levels of active GLP-1, stimulates insulin secretion and inhibits glucagon secretion, which results in lowering of glucose levels and improvement of the glycemic control in patients with type 2 diabetes.
4980 21437091 Advantages of these therapies include glucose-dependent enhancement of insulin secretion, infrequent instances of hypoglycemia, weight loss with GLP-1 receptor agonists, weight maintenance with DPP-IV inhibitors, decreased blood pressure, improvements in dyslipidemia, and potential beneficial effects on CV function.
4981 21437093 The nature of this increased accumulation of fat tissue, whether hyperplasia or hypertrophy, local or ectopic, is associated with deleterious perturbations including excess fatty acid secretion, increased production of inflammatory cytokines, and abnormal adipocyte hormone signaling resulting in insulin resistance.
4982 21242957 We generated ?-cell-specific VHL-knockout mice using the Cre-loxP recombination system driven by the rat insulin promoter to assess the role of VHL in glucose homeostasis and ?-cell function.
4983 21242957 VHL deletion in the pancreatic ?-cells led to impaired glucose tolerance due to defects in glucose-stimulated insulin secretion and ?-cell mass with age.
4984 21249428 We sought to evaluate the role of miR-146a expression along with its downstream proinflammatory signals in relation to glycemic control and insulin resistance.
4985 21274633 These findings suggest that CHOP expression is independent of the development of insulitis and diabetes but might affect the early production of insulin autoantibodies in the NOD mouse.
4986 21330636 With GIP alone, glucose was lowered slightly (P = 0.0021); insulin and C-peptide were stimulated to a lesser degree than with GLP-1 (P < 0.001).
4987 21330636 Adding GIP to GLP-1 did not further enhance the insulinotropic activity of GLP-1 (insulin, P = 0.90; C-peptide, P = 0.85).
4988 21346175 Male TPL2KO and wild-type (WT) littermates were fed a low-fat diet or a high-fat diet to investigate the effect of TPL2 deletion on obesity, inflammation, and insulin sensitivity.
4989 21357464 Knockdown of hepatic LIPIN2 in DIO mice reduced fasting hyperglycemia and improved hepatic insulin signaling.
4990 21357464 Conversely, overexpression of LIPIN2 impaired hepatic insulin signaling in a phosphatidic acid phosphatase activity-dependent manner.
4991 21378173 Human skeletal muscle cells were cultured for up to 24 h with tumor necrosis factor (TNF)-? to induce insulin resistance, and mRNA expression for cytokines was analyzed and compared with controls (without TNF-?).
4992 21378177 Mice harboring CD36-specific deletion in hematopoietic-derived cells (HSC CD36KO) fed an HFD displayed improved insulin signaling and reduced macrophage infiltration in adipose tissue compared with wild-type mice, but this did not translate into protection against HFD-induced whole-body insulin resistance.
4993 21386087 Fao or HepG2 cells exposed to TNF, anisomycin, or sphingomyelinase demonstrated rapid transactivation of ErbB receptors leading to PI3-kinase/Akt activation and IRS-1 serine phosphorylation. p38MAPK inhibition either by SB203580, by small interfering RNA, or by DN-p38MAPK? decreased ErbB receptors transactivation and IRS-1 serine phosphorylation and partially restored insulin-stimulated IRS-1 tyrosine phosphorylation.
4994 21411514 Congenital hyperinsulinism in infancy (CHI) is characterized by unregulated insulin secretion from pancreatic ?-cells; severe forms are associated with defects in ABCC8 and KCNJ11 genes encoding sulfonylurea receptor 1 (SUR1) and Kir6.2 subunits, which form ATP-sensitive K(+) (K(ATP)) channels in ?-cells.
4995 21448321 Reduced adiponectin could contribute to insulin resistance in these patients.
4996 21448349 Administration of YQZMT induced dose- and time-dependent changes in insulin resistance, glucose and lipid profile, and reduced levels of FFA, TNF-? and IL-6 in the type 2 diabetic rats.
4997 21448434 Insulin-degrading enzyme (IDE) is a thiol sensitive peptidase that degrades insulin and amyloid ?, and has been linked to type 2 diabetes mellitus and Alzheimer's disease.
4998 21099258 As compared with the diabetic control rats, effects of chitosan oligosaccharide for 12 weeks in the diabetic rats were summarized as follows; (1) the blood glucose concentrations fell significantly and it was confirmed by decreased glycated hemoglobin, (2) the plasma C-peptide was increased and provided elevated degree of insulin secretion, and (3) relatively well reconstructed pancreatic islet with ?-cells and additional insulin-immunolabeled cells in the pancreatic acinus and in the intercalated duct were observed.
4999 21099291 In parallel, we also investigated the subcellular localization of polypyrimidine tract-binding protein 1 (PTBP1), whose nucleocytoplasmic translocation is involved in the rapid posttranscriptional up-regulation of insulin biosynthesis following islet stimulation with glucose and GLP-1.
5000 21099294 Genome wide association studies have identified the islet-restricted zinc transporter ZnT8 (SLC30A8) as a likely player in the control of insulin secretion and the risk of developing type 2 diabetes.
5001 21099304 We have also identified MafA, a potent Insulin gene regulator, as the first direct target of Isl-1 in ?-cells.
5002 21099312 INS-1E cells or primary rat pancreatic islets were used to study the effect of AAT on insulin secretion after glucose, glucagon-like peptide-1 (GLP-1) and forskolin stimulation and on cytokine-mediated apoptosis.
5003 21099312 We found that AAT increases insulin secretion in a glucose-dependent manner, potentiates the effect of GLP-1 and forskolin and neutralizes the inhibitory effect of clonidine on insulin secretion.
5004 21099312 Our findings show that AAT stimulates insulin secretion and protects ?-cells against cytokine-induced apoptosis, and these effects of AAT seem to be mediated through the cAMP pathway.
5005 21099312 In view of these novel findings we suggest that AAT may represent a novel anti-inflammatory compound to protect ?-cells under the immunological attack in T1D but also therapeutic strategy to potentiate insulin secretion in type 2 diabetes (T2D).
5006 21451535 Protein kinase C inhibitors are able to overcome insulin resistance, offering new hopes for the treatment of the condition.
5007 19131467 The aim of this study was to test whether being born small for gestational age (SGA) has an impact on adiponectin and leptin levels and the IGF system in relation to insulin sensitivity, taking into consideration the severity of growth restriction.
5008 21189360 To determine whether serine/threonine ROCK1 is activated by insulin in vivo in humans and whether impaired activation of ROCK1 could play a role in the pathogenesis of insulin resistance, we measured the activity of ROCK1 and the protein content of the Rho family in vastus lateralis muscle of lean, obese nondiabetic, and obese type 2 diabetic subjects.
5009 21189360 Insulin increased ROCK1 activity 2.1-fold in lean and 1.7-fold in obese nondiabetic subjects in muscle.
5010 21189360 However, ROCK1 activity did not increase in response to insulin in muscle of obese type 2 diabetic subjects without change in ROCK1 protein levels.
5011 21099278 Cast (RIP) islets had modestly reduced expression of Rab3a and other critical components in the late steps of insulin exocytosis.
5012 21099282 The role and mechanism of phosphatidylinositol 3-OH (PI3) kinase as a regulator of insulin secretion is much debated.
5013 21099282 More recent studies, including our own recently published work, have begun to investigate PI3 kinase isoform-specific mechanisms regulating insulin secretion.
5014 21099282 Building on our previous work demonstrating that mice lacking a G-protein coupled PI3 kinase catalytic subunit (p110? -/-) lack first phase insulin secretion and display a blunted second phase of secretion, we have now elucidated the mechanism by which this PI3 kinase isoform acts as a positive regulator of insulin secretion.
5015 21353873 Activins signaling, which is mediated by ALK4 and 7 together with ActRIIA and IIB, plays a critical role in glucose-stimulated insulin secretion, development/neogenesis, and glucose homeostatic control of pancreatic endocrine cells; the insulin gene is regulated by these signaling pathways via ALK7, which is a receptor for Activins AB and B and Nodal.
5016 21441927 Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis.
5017 21441927 Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation.
5018 21461562 ZnT-8 has been suggested as a potential candidate in the regulation of insulin secretion in pancreatic ?-cells.
5019 10751221 PKCalpha, PKCdelta, PKCepsilon, and PKCmu isoforms found in preglomerular vessels were upregulated by captopril and high insulin doses, respectively, whereas no such regulation occurred in glomeruli.
5020 15113752 Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) are ligand-activated transcription factors that regulate cell growth, inflammation, lipid metabolism, and insulin sensitivity.
5021 15692059 Eight weeks after the induction of diabetes, renal mRNA levels of B2KR, CTGF, and TGF-beta as well as protein levels of CTGF and TGF-betaRII were measured in control (C), diabetic (D), and insulin-treated diabetic (D+I) rats.
5022 17567939 Insulin increased protein kinase C (PKC) activity and caused G protein-coupled receptor kinase 2 (GRK2) translocation to the membranes.
5023 17567939 Tyrosine kinase inhibitor genistein and phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked insulin-mediated PKC activation and GRK2 membranous translocation.
5024 17567939 In conclusion, insulin-induced D1R desensitization involves PI3K, PKC, and GRK2.
5025 18417539 A lower dose of fatty acids that leads to intracellular lipid accumulation but does not change baseline NHE3 is sufficient to abolish the stimulation of NHE3 by insulin and to partially block the stimulation of NHE3 by glucocorticoid hormones; acid regulation of NHE3 in lipid-loaded OKP cells is not affected.
5026 19452132 Nevertheless, activity of glucose-6-phosphatase in the liver was stimulated by insulin treatment to diabetic and arsenic-fed rats.
5027 20044046 In vitro analysis corroborated a negative effect of insulin on osteoclast recruitment, maturation and the expression levels of c-fos and RANK transcripts.
5028 20051463 EDC3, a component of the mRNA decay and translation repression pathway associated with mRNA processing bodies, was shown to be phosphorylated by AKT downstream of insulin signaling.
5029 20067955 Abnormal cellular cholesterol handling in islets may contribute to beta-cell dysfunction in type 2 diabetes. beta-Cell deficiency for the ATP binding cassette transporter A1 (ABCA1), which mediates the efflux of cellular cholesterol, leads to altered intracellular cholesterol homeostasis and impaired insulin secretion in mice.
5030 20067957 Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity.
5031 20067957 Association of ADIPOQ SNPs with plasma adiponectin was replicated, and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR.
5032 20068130 The present study investigates whether lipocalin-2 deficiency or replenishment with this adipokine has any impact on systemic insulin sensitivity and the underlying mechanisms.
5033 20068130 On the other hand, the expression and activity of 12-lipoxygenase, an enzyme responsible for metabolizing arachidonic acid, and the production of tumor necrosis factor-alpha (TNF-alpha), a critical insulin resistance-inducing factor, are largely inhibited by lipocalin-2 deficiency.
5034 20068130 Moreover, treatment with TNF-alpha neutralization antibody or CDC significantly attenuated the differences of insulin sensitivity between wild-type and Lcn2-KO mice.
5035 20855609 Leptin monotherapy reverses the deadly consequences and improves several of the metabolic imbalances caused by insulin-deficient type 1 diabetes (T1D) in rodents.
5036 20855609 Here, we report that intracerebroventricular (icv) infusion of leptin reverses lethality and greatly improves hyperglycemia, hyperglucagonemia, hyperketonemia, and polyuria caused by insulin deficiency in mice.
5037 20855609 Pancreatic ?-cell regeneration does not underlie these beneficial effects of leptin, because circulating insulin levels were undetectable at basal levels and following a glucose overload.
5038 21207203 Increased protein intake does not increase plasma glucose, but increases the insulin response and results in a significant reduction in hemoglobin A(1c).
5039 21311858 Treatment with TNF-? augmented the activity ratios of both GS and GP, and impaired insulin stimulation of glycogen synthesis in wild-type myocytes, whereas Ptp1b (-/-) myocytes restored this inhibitory effect.
5040 21327868 Circulating SAA and SAP did not decrease in either insulin-treated group, but IL-6 levels fell in the glargine-treated mice.
5041 21327868 While chronic insulin administration did not decrease SAA and SAP, administration of glargine but not detemir insulin improved dyslipidaemia, IL-6 levels and atherosclerosis, and both insulins reduced macrophage accumulation in visceral adipose tissue.
5042 21336532 This suggests that some level of insulin resistance is needed to see deleterious effects of low adiponectin.
5043 21472332 These data indicate that mTOR contributes to insulin resistance and chronic liver inflammation, and may play an important role in the development and progression of NAFLD.
5044 21472564 Defects in the protein-protein interactions involving IRS-1 may lead to the development of insulin resistance and type 2 diabetes.
5045 20374961 Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy balance and glucose homeostasis and express leptin and insulin receptors.
5046 20466847 Genetic and biological studies have shown that reductions in IRS1 and/or IRS2 protein levels are associated with insulin resistance.
5047 20466847 In this study we have shown that proteasome degradation of IRS1, but not of IRS2, is involved in HG-induced insulin resistance in Chinese hamster ovary (CHO) cells as well as in primary hepatocytes.
5048 20466847 In contrast to the insulin-induced degradation of IRS1, HG-induced degradation of IRS1 did not require IR signaling or phosphatidylinositol 3-kinase/Akt activity.
5049 21252242 However, in multivariate analyses, SHBG levels varied significantly with rs1799941 and rs727428 genotype after controlling for body mass index, non-SHBG-bound testosterone, and homeostasis model for insulin resistance.
5050 21252242 Although SHBG SNPs associated with type 2 diabetes mellitus do not appear to be associated with PCOS status, rs1799941 and rs727428 genotypes are associated with SHBG levels independent of the effects of insulin resistance and obesity.
5051 21295117 Administration of insulin to diabetic rats tended to restore the cevimeline-induced translocation of AQP5.
5052 21335550 We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic ? cells and its consequences for preproinsulin (Ins1, Ins2) gene expression.
5053 21393865 Furthermore, striated muscle activator of Rho signaling (STARS), an activator of SRF, was upregulated in T2D and FH(+) and was inversely correlated with insulin sensitivity.
5054 21393865 Overexpression of MKL1 or reduction in G-actin decreased insulin-stimulated Akt phosphorylation, whereas reduction of STARS expression increased insulin signaling and glucose uptake.
5055 21464101 In vitro, PLP protected islets against STZ-induced changes in viability, insulin secretion, prevented increase in free radical levels and normalized mRNA of Insulin and Pdx1.
5056 21479175 Treatment of the isolated fat body with human insulin in an in vitro culture system increased total sugar in the fat body and stimulated Akt phosphorylation.
5057 21479350 The administration of JFEE or JFBE to streptozotocin (STZ)-diabetic rats significantly reduced fasting blood glucose (FBG) from 200 to 56 and 79 mg%, respectively; elevated insulin from 10.8 to 19.5 and 15.1 µU/ml, respectively; decreased lipid peroxides from 7.3 to 5.4 and 5.9 nmol/ml, respectively; decreased %glycosylated hemoglobin A1C (%HbA1C) from 6.8 to 4.5 and 5.0%, respectively; and increased total protein content from 2.5 to 6.3 and 5.7 mg%, respectively.
5058 18974244 Activation of various kinases modulates adipocyte transcription factors, including peroxisome proliferator-activated receptor-gamma and NFkappaB, attenuating insulin signaling and increasing adipocytokine and free fatty acid secretion.
5059 19249087 This study reveals a conserved role for the B56 regulatory subunit in regulating insulin signaling through AKT dephosphorylation, thereby having widespread implications in cancer and diabetes research.
5060 21317886 Our results thus provide the first evidence to our knowledge that XBP-1s, through its interaction with FoxO1, can bypass hepatic insulin resistance independent of its effects on ER folding capacity, suggesting a new therapeutic approach for the treatment of type 2 diabetes.
5061 21321840 This prospective study indicates that change in amount body fat and levels of inflammatory cytokines, such as IL-6, contribute to change in insulin resistance over time in type 1 diabetes patients with and without diabetic nephropathy.
5062 17036923 Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals.
5063 20871474 Propranolol, a ?-adrenergic receptor antagonist, significantly (P<0.04) reduced the stimulatory effect of orexin B on insulin secretion.
5064 21261565 AREAS COVERED: The present review considers: i) the role of leptin, adiponectin, ghrelin and NPY in patients with T2DM, and, ii) the effect of insulin as well as oral hypoglycemic, antihypertensive, hypolipidemic, antiobesity and antiplatelet agents on these peptides in patients with T2DM.
5065 21428694 Since adiponectin expression has been correlated with insulin resistance, obesity and diabetes, GSTK1 expression level which is negatively correlated with obesity in mice and human adipose tissues may be an important factor in these metabolic disorders.
5066 21428694 Furthermore, a polymorphism in the hGSTK1 promoter has been associated with insulin secretion and fat deposition.
5067 20626638 The pancreatic duodenal homeobox-1 (PDX-1) expression might also be different because it links glucose metabolism to the regulation of insulin gene transcription in the pancreas. ?
5068 20651470 Adiponectin has emerged over the last decade as a key adipokine linking obesity, insulin resistance, and Type 2 diabetes.
5069 21161163 We investigated whether oltipraz, a nuclear respiratory factor 2 alpha subunit (NRF2) activator, improves insulin sensitivity and prevents the development of obesity in mice.
5070 21190014 Insulin action is purportedly modulated by Drosophila tribbles homologue 3 (TRIB3), which in vitro prevents thymoma viral proto-oncogene (AKT) and peroxisome proliferator-activated receptor-? (PPAR-?) activation.
5071 21190014 These data suggest that TRIB3 inhibition improves insulin sensitivity in vivo primarily in a PPAR-?-dependent manner and without any change in AKT2 activity.
5072 21194385 Cortical neurons pretreated with insulin, but not glucose or PA, exhibited blunted phosphorylation of Akt, p70S6K, and GSK-3? with no change detected in ERK.
5073 21194385 Inhibition of the phosphatidylinositol 3-kinase (PI3-K) pathway during insulin pretreatment restored acute insulin-mediated Akt phosphorylation.
5074 21210076 These data show that deletion of IL-10 from the haematopoietic system does not potentiate high-fat diet-induced inflammation or insulin resistance.
5075 21229348 Insulin resistance is associated with reduced serum adiponectin and increased albuminuria levels.
5076 21500593 To explore the possible mechanism of nerve growth factor (NGF) mixed insulin on the angiogenesis of burn wounds and the effect on the expressions of Bcl-2 and Bax in diabetic rats.
5077 21159217 Both apoB and apoA1 were significantly associated with obesity when age, sex, diastolic blood pressure, homocysteine, diabetes, and insulin resistance were controlled for.
5078 21325151 Variants of ADRA2A affect gene transcription and expression and are associated with insulin release and risk for type 2 diabetes.
5079 21436039 Mice lacking p110? (Pik3cg(-/-)), the catalytic subunit of PI3K?, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals.
5080 17878241 AdipoR2 mRNA expression in both visceral and subcutaneous fat is positively associated with circulating adiponectin and HDL levels but negatively associated with obesity as well as parameters of insulin resistance, glycemia, and other lipid levels before and after adjustment for fat mass.
5081 19153269 PM(2.5) exposure induced signaling abnormalities characteristic of insulin resistance, including decreased Akt and endothelial nitric oxide synthase phosphorylation in the endothelium and increased protein kinase C expression.
5082 20959527 ANP was investigated for short- and long-term effects on insulin secretion and mechanisms regulating secretion in isolated rat pancreatic islets.
5083 21162119 Factors that regulate PDK4 mRNA expression include plasma corticosterone, insulin and free fatty acids.
5084 21205932 We showed previously that insulin receptor signaling is diminished in retinas of animal models of diabetes and that downstream Akt signaling is involved in insulin-mediated retinal neuronal survival.
5085 21205932 To investigate the mechanism by which PKC impairs insulin-stimulated Akt activity, we assessed various upstream mediators of Akt signaling.
5086 21205932 Thus, we next investigated a biophysical mechanism by which insulin signaling could be disrupted and found that disruption of lipid microdomains via cholesterol depletion blocks insulin-induced Akt activation and reduces insulin receptor tyrosine phosphorylation.
5087 21266328 A defining feature of muscle and fat vis-ą-vis insulin signaling is that they both express the insulin-sensitive glucose transporter Glut4.
5088 21266332 SUMO1 impairs glucose-stimulated insulin secretion by blunting the ?-cell exocytotic response to Ca(2+).
5089 21266332 Conversely, SENP1 knockdown impairs exocytosis at stimulatory glucose levels and blunts glucose-dependent insulin secretion from mouse and human islets.
5090 21266332 The SUMO protease, SENP1, is required for glucose-dependent insulin secretion.
5091 21270239 Knockdown of pericentrin in adipocytes had no effect on proximal insulin signaling but produced a twofold impairment in insulin-stimulated glucose uptake, approximately commensurate with an associated defect in cell proliferation and adipogenesis.
5092 21270239 Partial failure of adipocyte differentiation may contribute to this, but pericentrin deficiency does not impair proximal insulin action in adipocytes.
5093 21282361 Although adipocyte-derived murine resistin links insulin resistance to obesity, the role of human resistin, predominantly expressed in mononuclear cells and induced by inflammatory signals, remains unclear.
5094 21282361 Thus, human resistin may link insulin resistance to inflammatory diseases such as obesity, type 2 diabetes, and atherosclerosis.
5095 21282367 Insulin resistance in diet-induced obesity (DIO) is associated with a chronic systemic low-grade inflammation, and Toll-like receptor 4 (TLR4) plays an important role in the link among insulin resistance, inflammation, and obesity.
5096 21282367 The current study aimed to analyze the effect of exercise on TLR4 expression and activation in obese rats and its consequences on insulin sensitivity and signaling.
5097 21282367 However, both acute and chronic exercise blunted TLR4 signaling in these tissues, including a reduction in JNK and IKK? phosphorylation and IRS-1 serine 307 phosphorylation, and, in parallel, improved insulin-induced IR, IRS-1 tyrosine phosphorylation, and Akt serine phosphorylation, and reduced LPS serum levels.
5098 21282370 Expression of PTRF also is hormonally regulated because treatment of mice with insulin leads to a decrease in expression, whereas isoproterenol increases expression in WAT.
5099 21289205 Adiponectin receptor-1 (AdipoR1) expression in skeletal muscle has been suggested to play an important role in insulin resistance and diabetes.
5100 21289215 Induction of diabetes also increased phosphorylation of tuberin in association with mTOR activation (measured by p70S6K phosphorylation), inactivation of Bcl-2, increased cytosolic cytochrome c expression, activation of caspase 3, and cleavage of PARP; insulin treatment prevented these changes.
5101 21356182 Interestingly, genome-wide transcription profiling identified functional networks of genes, in which key regulators of weight homeostasis (PPARs, glucocoricoids, CEBPs, estradiol), steroid hormone functions (glucocoricoids, estradiol, NCOA3) and insulin signaling (HNF4A, CEBPs, PPARG) occupied central positions.
5102 21357472 SGLT2 knockout mice were protected from HFD-induced hyperglycemia and glucose intolerance and had reduced plasma insulin concentrations compared with controls.
5103 21357472 On the db/db background, SGLT2 deletion prevented fasting hyperglycemia, and plasma insulin levels were also dramatically improved.
5104 21427225 Leptin inhibits insulin secretion from pancreatic ?-cells, and in turn, insulin stimulates leptin biosynthesis and secretion from adipose tissue.
5105 21427225 At the molecular level, leptin acts through various pathways, which in combination confer inhibitory effects on insulin biosynthesis and secretion.
5106 21427225 In addition, glucose-induced insulin secretion was inhibited by nuclear inhibitor of PP-1 and calyculin A, which was in part mediated by a reduction of PP-1-dependent calcium influx into INS-1 ?-cells.
5107 21126901 The present study aimed to assess the prevalence of insulin resistance and T2D, and their association with adiponectin and leptin, in Afro-Caribbean men and women with HIV infection.
5108 21126901 Insulin resistance was independently associated with adiponectin in women and with leptin in men.
5109 21245029 GIP acted synergistically with insulin to increase neutral lipid accumulation during progression of 3T3-L1 preadipocytes to the adipocyte phenotype.
5110 21245029 Taken together, these studies show that GIP and insulin act in a synergistic manner on 3T3-L1 cell development and that adipocyte GIPR expression is upregulated through a mechanism involving interactions between PPAR? and a GIPR promoter region containing an acetylated histone region.
5111 21330367 Transgenic mice that lack neuronal insulin receptor expression in the brain (NIRKO mice) were unable to mount the full hyperthermic response to IGF-1, suggesting that the IGF-1 mediated hyperthermia is partly dependent on expression of functional neuronal insulin receptors.
5112 21330367 These data indicate a novel thermoregulatory role for both IGF-1R and neuronal insulin receptors in IGF-1 activation of BAT and hyperthermia.
5113 21484566 They also reduce the secretion of inflammatory cytokines such as TNF? and increase the plasma level of adiponectin, which increases insulin sensitivity in liver and skeletal muscle.
5114 21484571 Nampt plays an important role in the regulation of insulin secretion insulin secretion in pancreatic ?-cells.
5115 21484573 CNTF is a gp130 ligand that has been found to act centrally and peripherally to promote weight loss and insulin sensitivity in both human and rodent models.
5116 21484576 Inhibitors of FBPase are expected to fulfill an unmet medical need because the majority of current antidiabetic medications act primarily on insulin resistance or insulin insufficiency and do not reduce gluconeogenesis effectively or in a direct manner.
5117 21484579 Consequently, they stimulate insulin biosynthesis and secretion, enhance hepatic glucose uptake, and augment glucose metabolism and related processes in other glucokinase-expressing cells.
5118 21497092 We found that postembryonic antagonism of Ptf1a, a master regulator of pancreatic development and acinar cell fate specification, induced the expression of endocrine genes including insulin in the exocrine compartment.
5119 9166685 A functional role for the beta-cell leptin receptor is indicated by our observation that leptin (100 ng/ml) suppressed the secretion of insulin from islets isolated from ob/ob mice.
5120 9166685 Taken together, these observations indicate an important physiological role for leptin as an inhibitor of insulin secretion and lead us to propose that the failure of leptin to inhibit insulin secretion from the beta-cells of ob/ob and db/db mice may explain, in part, the development of hyperinsulinemia, insulin resistance, and the progression to NIDDM.
5121 9972293 On the basis of this homology, we report the synthesis and initial characterization of a chimeric peptide (Black Widow GLP-1) that stimulates Ca2+ signaling and insulin secretion in human beta-cells and MIN6 insulinoma cells.
5122 10022436 Previously we demonstrated the expression of the long form of the leptin receptor in rodent pancreatic beta-cells and an inhibition of insulin secretion by leptin via activation of ATP-sensitive potassium channels.
5123 10022436 Leptin (6.25 nM) suppressed insulin secretion of normal islets by 20% at 5.6 mM glucose.
5124 10022436 Proinsulin messenger ribonucleic acid expression in islets was inhibited by leptin at 11.1 mM, but not at 5.6 mM glucose.
5125 10022436 Leptin also reduced proinsulin messenger ribonucleic acid levels that were increased in islets by treatment with 10 nM glucagon-like peptide-1 in the presence of either 5.6 or 11.1 mM glucose.
5126 11845326 In INS-1 cells over-expressing the beta-cell GLP-1 receptor (GLP-1-R), we have shown, by radioimmune assay and bioassay of conditioned medium, that an autocrine signaling mechanism of hormone action exists whereby self-secreted GLP-1 acts as a competence factor in support of insulin gene transcription.
5127 11845326 INS-1 cells also exhibit insulin gene promoter activity, as assayed in cells transfected with a rat insulin gene I promoter-luciferase construct (RIP1-Luc).
5128 15671479 Foxo1, a member of the Fox0 subfamily of winged-helix forkhead transcription factors, is a target of insulin and insulin-like growth factor-1 (IGF-1) signal transduction pathways that activate protein kinase B (PKB) in pancreatic beta cells.
5129 20966915 Therefore, we investigated whether genetic variation within the CD36 gene locus affects insulin resistance in a well-phenotyped cohort of white European subjects at increased risk for type 2 diabetes.
5130 20966915 In the long run, genetic variation within the CD36 locus may contribute to metabolic disease via its effect on body adiposity, but not via an independent effect on insulin sensitivity.
5131 21087152 And in vitro, in 3T3-L1 adipocytes, insulin-induced (1.0?mmol/liter) insulin resistance significantly decreased VLDLR mRNA expression.
5132 21219874 Although artepillin C had no effects on the insulin signaling cascade, artepillin C enhanced the expression and plasma membrane translocation of GLUT1 and GLUT4 in mature adipocytes.
5133 20717889 Final maturation to islet-specific cells is achieved by co-culturing the ESC-derived pancreatic endocrine cells with endothelial cells, which resulted in Insulin 1 upregulation in 60% of the cell population, along with high levels of IAPP and Glut2.
5134 21218505 the mechanism by which islet amyloid polypeptide (IAPP) inhibits insulin release is unclear.
5135 21219237 Given that some of the modifications introduced into insulin analogues are located in a domain involved in a potential interaction with the insulin-like growth factor-I receptor (IGF-IR), it has been postulated that certain analogues may display IGF-I-like activities.
5136 21411512 The purpose of the current study was to determine whether leptin treatment has weight loss-independent effects on insulin action in obese subjects with type 2 diabetes.
5137 21441444 The insulinogenic index (the ratio of insulin to glucose) decreased in T1D+ patients during blockade of endogenous GLP-1 receptor action.
5138 21464440 Activin A effects on insulin secretion and inflammation were tested in human pancreatic islet cells. 1) In patients with acute MI, serum levels of activin A were significantly higher in those with abnormal glucose regulation (AGR) compared with those with normal glucose regulation.
5139 21464440 Activin A levels were associated with the presence of AGR 3 months later (adjusted odds ratio 5.1 [95% CI 1.73-15.17], P = 0.003). 2) In endothelial cells, glucose enhanced the release of activin A, whereas activin A attenuated the release of interleukin (IL)-8 and enhanced the mRNA levels of the antioxidant metallothionein. 3) In islet cells, activin A attenuated the suppressive effect of inflammatory cytokines on insulin release, counteracted the ability of these inflammatory cytokines to induce mRNA expression of IL-8, and induced the expression of transforming growth factor-?.
5140 21464445 Pigment epithelium-derived factor (PEDF) is an adipocyte-secreted factor involved in the development of insulin resistance in obesity.
5141 21471511 In HepG2 cells, activation of mitogen-activated protein kinase-extracellular signal-related kinase signaling by nobiletin or insulin increased LDLR and decreased MTP and DGAT1/2 mRNA, resulting in marked inhibition of apoB100 secretion.
5142 21478464 We investigated the roles of hepatic TR4 in the regulation of lipogenesis and insulin sensitivity in vivo and in vitro.
5143 21478464 The results show that the suppression of SCD1 via loss of TR4 resulted in reduced fat mass and increased insulin sensitivity with increased ?-oxidation and decreased lipogenic gene expression.
5144 21517657 Incretin hormones, such as glucagon-like peptide-1 (GLP-1), play a crucial role in modulating insulin and glucagon secretion, as well as regulating appetite, gastric emptying, and pancreatic beta cell function.
5145 21525818 Recently, it has been shown that SIRT1 plays key roles in the regulation of lipid and glucose homeostasis, control of insulin secretion and sensitivity, antiinflammatory effects, control of oxidative stress and the improvements in endothelial function that result due to increased mitochondrial biogenesis and ?-oxidation capacity.
5146 19816414 These data suggest that RBP4 may regulate adiposity, and p85 expression in obese-T2DM, thus providing a link to impaired insulin signaling and diabetes in severely obese patients.
5147 19906798 Pharmacologic studies show that FGF21 has broad metabolic actions in obese rodents and primates that include enhancing insulin sensitivity, decreasing triglyceride concentrations, and causing weight loss.
5148 21281610 Insulin administration restored the blood glucose level in DM rats but suppressed PP-2A activity, resulting in the PHF-1 sites of tau not being dephosphorylated.
5149 20719094 Uncoupling protein 2 (UCP2) is a member of the uncoupling protein family, which is localized to the inner mitochondrial membrane and negatively regulates insulin secretion in the pancreatic ?-cells.
5150 21087662 Ahsg has a second physiological function in regulating how insulin signals through its receptor, a transmembrane tyrosine kinase.
5151 21185419 Although previous animal studies showed that osteocalcin stimulated the expression of insulin in islets and of adiponectin in adipocytes with increased insulin secretion and sensitivity, the associations of serum osteocalcin with those parameters remain unclear in humans.
5152 21400856 These inflammatory mediators inhibit insulin signaling with several mechanisms, such as serine-phosphorylation of IRS-1, the induction of SOCS3 and the activation of JNK or NFkappaB signaling in insulin-target tissues.
5153 21423295 Untreated HFD-STZ rats showed elevated fasting blood glucose, insulin, homeostasis model assessment (HOMA) index, triglycerides (TGs), low-density lipoprotein cholesterol (LDL), and total serum cholesterol (TC), with a decrease in high-density lipoprotein cholesterol (HDL) and adiponectin levels (p < 0.001).
5154 21537421 Recent animal studies highlighted a possible interaction between chronic PDE5 inhibition and glucose homeostasis which occurs through a marked improvement of high fat diet induced insulin resistance.
5155 18487449 Downregulation of PAT proteins also produced insulin resistance, as indicated by decreased insulin stimulation of Akt phosphorylation (P < 0.001).
5156 20032314 Inhibition of G6PD with siRNA led to increased ROS and apoptosis, decreased proliferation, and impaired insulin secretion.
5157 20103738 Hepatic phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser(473) phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW (P < 0.05 vs.
5158 20150287 GSTA4 expression is selectively downregulated in adipose tissue of obese insulin-resistant C57BL/6J mice and in human obesity-linked insulin resistance.
5159 20150287 These results indicate that downregulation of GSTA4 in adipose tissue leads to increased protein carbonylation, ROS production, and mitochondrial dysfunction and may contribute to the development of insulin resistance and type 2 diabetes.
5160 20150288 In the absence of insulin, gAd stimulated AMPK Thr172 phosphorylation, SNAT2 protein expression, and system A activity.
5161 20167843 PTP localized to mitochondrion 1 (PTPMT1) is a recently discovered dual-specificity phosphatase that has been implicated in the regulation of insulin secretion.
5162 20179247 Toll-like receptor 4 (TLR4), a protein integral to innate immunity, is elevated in skeletal muscle of obese and type 2 diabetic humans and has been implicated in the development of lipid-induced insulin resistance.
5163 20185807 Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity).
5164 20185809 Real-time PCR identified a positive correlation between ASK1 expression in skeletal muscle biopsies and in vivo insulin action (P = 0.02, r = 0.23), and the risk allele for rs1570056 was associated with lower ASK1 expression (P = 0.003, r = -0.22).
5165 20185813 Eleven-week-old GIPR(dn) transgenic pigs exhibited significantly reduced oral glucose tolerance due to delayed insulin secretion, whereas intravenous glucose tolerance and pancreatic beta-cell mass were not different from controls.
5166 20185813 The insulinotropic effect of GIP was significantly reduced, whereas insulin secretion in response to the GLP-1 receptor agonist exendin-4 was enhanced in GIPR(dn) transgenic versus control pigs.
5167 20200310 In view of the previously described anti-inflammatory effects of insulin, we investigated the potential suppressive effect of insulin on plasma concentrations and expression of the chemokines, monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normal T-cell expressed and secreted (RANTES) and their receptors, chemokine receptor (CCR)-2 and CCR-5, in mononuclear cells (MNCs).
5168 20200310 Insulin infusion significantly suppressed the plasma concentrations of MCP-1, eotaxin, and RANTES and the expression of RANTES, macrophage inflammatory protein (MIP)-1beta, CCR-2, and CCR-5 in MNCs at 2 and 4 h.
5169 20200310 A low-dose infusion of insulin suppresses the plasma concentration of key chemokines, MCP-1, and RANTES, and the expression of their respective receptors, CCR-2 and CCR-5, in MNCs.
5170 20200310 Insulin also suppresses the expression of RANTES and MIP-1beta in MNCs.
5171 20215429 The primary goal of this study was to determine whether endogenous GLP-1 regulates insulin secretion in type 2 diabetes.
5172 20215429 Blocking the action of GLP-1 suppressed postprandial insulin secretion similarly in the diabetic and nondiabetic subjects (25 +/- 4% vs. 27 +/- 8%).
5173 20215429 However, Ex-9 also reduced the insulin response to intravenous glucose (25 +/- 5% vs. 26 +/- 7%; diabetic vs. nondiabetic subjects), when plasma GLP-1 levels were undetectable.
5174 20215429 These findings indicate that in patients with well-controlled diabetes, the relative effects of enteral stimuli and endogenous GLP-1 to enhance insulin release are retained and comparable with those in nondiabetic subjects.
5175 20388924 In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance.
5176 20513317 A formulation containing 14 kDa polysialic acid (PSA)-recombinant human insulin conjugate was manufactured at Lipoxen PLC and transferred to Glide Pharma.
5177 21161439 Linoleic acid also dose-dependently reduced mitochondrial membrane potential (??m) and significantly promoted cytochrome c release from mitochondria in both 11.1 mM glucose and 25 mM glucose culture medium, further reducing glucose-stimulated insulin secretion, which is dependent on normal mitochondrial function.
5178 21376123 Multivariate logistic regression analysis revealed that the increase of urinary albumin excretion correlated significantly with the homeostasis model assessment of insulin resistance and systolic pressure.
5179 21376123 The rise in insulin resistance and systolic pressure may contribute to the increase of urinary albumin excretion in renal transplant recipients.
5180 10931418 The acute insulin response to intravenous calcium stimulation (CaAIR) was determined in 9 patients <20 years with diffuse hyperinsulinism caused by defective beta-cell sulfonylurea receptor (SUR1(-/-)), 3 patients with focal congenital hyperinsulinism (6 weeks to 18 months), a 10-year-old with insulinoma, 5 with hyperinsulinism/hyperammonemia syndrome caused by defective glutamate dehydrogenase (6 months to 28 years), 4 SUR1(+/-) heterozygotes with no symptoms, and 9 normal adults.
5181 15983036 Murine resistin reduced insulin-stimulated glucose uptake, establishing the heart as a resistin target tissue.
5182 15983036 Notably, human resistin also impaired insulin action in mouse cardiomyocytes, providing the first evidence that human and mouse resistin homologs have similar functions.
5183 15983036 Remarkably, unlike native resistin, monomeric C26A resistin had no effect on basal or insulin-stimulated glucose uptake in mouse cardiomyocytes.
5184 16275148 Using the rat insulinoma RINm5F cell line, we report the first studies in insulin-secreting cells that IGFBP-3 selectively suppresses multiple, key intracellular phosphorelays.
5185 16428347 Streptozotocin-induced insulin-dependent diabetes (4 wk) and fasting (
5186 16428347 Our data expose differential regulation of acsl isoforms and cte1 in the heart, where acsl1 and cte1 are PPARalpha-regulated genes, whereas acsl6 is an insulin-regulated gene.
5187 17823261 Given the important role of insulin signaling in the regulation of myocardial size, we tested the hypothesis that augmentation of myocardial insulin signaling may play a role in PPAR-gamma ligand-induced cardiac hypertrophy.
5188 17823261 These data indicate that cardiac hypertrophy after PPAR-gamma agonist treatment can occur in the absence of myocardial insulin signaling and is likely secondary to the hemodynamic consequences of plasma volume expansion.
5189 18426862 The Q allele of ENPP1 K121Q is associated with hyperglycemia and insulin resistance in whites.
5190 18492747 The prevalence of insulin resistance increased with decreasing tertiles of adiponectin (from 10.9% in the third to 42.5% in the first tertile; P < 0.0001) and increasing tertiles of resistin (from 19.3 to 30.9%; P < 0.0001) and TNFalpha (from 18.8 to 32.0%; P < 0.0001).
5191 19029465 This might be explained by associations of vWF with type 2 diabetes mellitus and insulin resistance.
5192 19846171 Tumor necrosis factor alpha (TNFalpha) is a proinflammatory adipokine hypothesized to link obesity with insulin resistance.
5193 19846171 Functional studies suggest that TNFalpha acts through pathways involving adipokines and fatty acids to induce insulin resistance.
5194 19846171 We tested the hypothesis that the association of measures of TNFalpha activity with insulin resistance is independent of obesity and adipose tissue biomarkers.
5195 19846171 We conclude that, in a representative community sample, measures of TNFalpha activity are associated with insulin resistance, even after accounting for central adiposity and other adipose tissue biomarkers.
5196 20158571 MafA is a pancreatic transcriptional factor that controls ?-cell-specific transcription of the insulin gene.
5197 20158571 Importantly, the expression of MafA in PDMSCs xenotransplanted into immunocompromised mice improved the restoration of blood insulin levels to control values and greatly prolonged the survival of graft cells in immunocompromised mice with STZ-induced diabetes.
5198 20158571 In summary, these data suggest that MafA plays a novel role in the reprogramming of stem cells into pancreatic ?-progenitors, promotes the islet-like characteristics of PDMSCs, as well as functionally enhances insulin production to restore the regulation of blood glucose levels in transplanted grafts.
5199 21060977 We studied SCD1 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbidly obese patients and their association with insulin resistance, sterol regulatory element binding protein-1 (SREBP-1) and ATPase p97, proteins involved in SCD1 synthesis and degradation.
5200 21060977 In the morbidly obese patients, the VAT SCD1 protein levels were decreased in patients with higher insulin resistance (P = 0.007).
5201 21060977 However, SAT SCD1 protein levels were increased in morbidly obese patients with higher insulin resistance (P < 0.05).
5202 21060977 Multiple linear regressions in the morbidly obese patients showed that the variable associated with the SCD1 protein levels in VAT was insulin resistance, and the variables associated with SCD1 protein levels in SAT were body mass index (BMI) and ATPase p97.
5203 21099335 Somatostatin (SST) released from islet ?-cells inhibits both insulin and glucagon secretion but the role of this tonic inhibition is unclear.
5204 21172424 Glucose-stimulated insulin secretion (GSIS) by pancreatic ? cells is regulated by mitochondrial uncoupling protein-2 (UCP2), but opposing phenotypes, GSIS improvement and impairment, have been reported for different Ucp2-ablated mouse models.
5205 21277869 Inhibition of transient receptor potential vanilloid 1 (TRPV1) suppresses calcitonin gene-related peptide (CGRP) secretion in pancreatic nerve fiber cells, thereby stimulating insulin secretion.
5206 21277869 We examined the effects of repeat administration of the TRPV1 antagonist N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamidte monohydrochloride (BCTC) to ob/ob mice, a model of type 2 diabetes with insulin resistance, on whole body glucose and lipid metabolism.
5207 21325461 Recent studies in mice have demonstrated that insulin signaling in osteoblasts stimulates bone formation and reduces osteoprotegerin production; the latter results in an increase in bone resorption, which then leads to the release of undercarboxylated osteocalcin from bone.
5208 21325461 Undercarboxylated osteocalcin, in turn, enhances insulin sensitivity.
5209 21325461 Fourteen subjects underwent a 7-h stepped insulin infusion accompanied by a glucose clamp and somatostatin infusion along with replacement infusions of GH and glucagon, thus isolating possible effects of insulin on bone.
5210 21325461 However, measures of insulin sensitivity (glucose infusion and disappearance rates) correlated positively with C-terminal telopeptide of type I collagen levels.
5211 21325461 Acute changes in insulin levels, as occur during meals, do not regulate bone turnover, undercarboxylated osteocalcin, or osteoprotegerin levels.
5212 21347624 Concurrently, insulin signalling and subsequent insulin action were impaired and levels of gluconeogenic enzymes were increased by lon protein deficiency.
5213 21347624 Overproduction of lon protease restored mitochondrial function and also diminished the insulin resistance induced by treatment with cholesterol and palmitate.
5214 21347624 Here we have demonstrated that reduction of lon protease induced hepatic insulin resistance by lowering mitochondrial function.
5215 21436455 The effects of FGF19 are independent of the activity of either insulin or the protein kinase Akt and, instead, are mediated through a mitogen-activated protein kinase signaling pathway that activates components of the protein translation machinery and stimulates glycogen synthase activity.
5216 10763483 The administration of CCK to intact animals causes increase of insulin content in endocrinocytes of pancreatic islets, but does not affect the level of hypoglycemia.
5217 16814734 Individuals with a family history of type 2 diabetes display skeletal muscle insulin resistance and mitochondrial dysfunction; adiponectin levels strongly correlate with mtDNA content.
5218 16814734 Knockout of the adiponectin gene in mice is associated with insulin resistance and low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle.
5219 18497885 To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling.
5220 18497885 Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression.
5221 18497885 These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes.
5222 18927507 Our recent studies illustrate that the forkhead transcription factor FoxO1 acts in the liver to integrate hepatic insulin action to VLDL production.
5223 18927507 Augmented FoxO1 activity in insulin resistant livers promotes hepatic VLDL overproduction and predisposes to the development of hypertriglyceridemia.
5224 19038471 Combined, these results indicate that body fat, larger adipocytes, failure of insulin to suppress NEFAs, decreased adiponectin levels and inflammation markers in adipose tissue are associated with decreased insulin-stimulated glucose uptake and oxidation, which is an important component of reduced metabolic flexibility.
5225 20417156 Here, we identified dSH2B as the Drosophila homolog of SH2B1. dSH2B bound to Chico and directly promoted insulin-like signaling.
5226 20501674 FoxO1 targeted GRP78 gene for trans-activation via selective binding to an insulin responsive element in the GRP78 promoter.
5227 21454697 Insulin-stimulated translocation of the glucose transporter GLUT4 to the cell surface in fat and muscle cells is the basis for insulin-stimulated glucose transport.
5228 21540554 Unexpectedly, deletion of Glp1r in Gcgr-/- mice did not alter the improved oral glucose tolerance and increased insulin secretion characteristic of that genotype.
5229 21088934 To investigate insulin sensitivity within the liver, serine phosphorylation of IRS-1 (Ser307) and Akt (Ser473) and expression of gluconeogenic genes, PEPCK and G6Pase, were tested.
5230 21157114 Stepwise multiple linear regression analyses for serum HMW adiponectin revealed that the hemoglobin status was independently and significantly associated with serum HMW adiponectin levels as well as sex, age, body mass index (BMI), alcohol consumption, total cholesterol, triglycerides, high density lipoprotein cholesterol, antilipidemic medication, uric acid, serum gamma glutamyltransferase, and insulin resistance.
5231 21157114 In stratified analysis, mean serum HMW adiponectin levels were significantly and similarly decreased as hemoglobin levels increased in men, ages ? 65 years, BMI < 23.0 kg/m(2), alcohol drinkers, and lower insulin resistance, and there were significant interactions between the two groups for BMI, alcohol consumption and insulin resistance.
5232 21157114 Hemoglobin status is inversely associated with serum HMW adiponectin levels in community-dwelling persons, especially those aged ? 65 years, BMI < 23.0 kg/m(2), alcohol drinkers, and lower insulin resistance groups.
5233 21237153 GLP-1 activates pancreatic receptors resulting in improved glycemia through glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion.
5234 21489354 It is well documented that high blood homocysteine (Hcy) levels possibly contribute to insulin resistance through the induction of resistin and inhibition of adiponectin expression in mouce adipose tissue in vitro.
5235 21556362 The logistic regression analysis showed that fetuin-A were associated with elevated HOMA-IR and fasting serum insulin both among the participants with or without type 2 diabetes in the full adjusted analysis.
5236 21556362 Higher fetuin-A concentrations were associated with type 2 diabetes and insulin resistance in middle aged and elderly Chinese.
5237 18285525 Since elevated circulating RBP4 causes insulin resistance and glucose intolerance in mice, these findings suggest that increased TTR or alterations in RBP4-TTR binding may contribute to insulin resistance by stabilizing RBP4 at higher steady-state concentrations in circulation.
5238 18285525 Lowering TTR levels or interfering with RBP4-TTR binding may enhance insulin sensitivity in obesity and type 2 diabetes.
5239 18437353 The RBP4:transthyretin ratio correlated with HOMA-IR and fasting insulin in controls.
5240 19450513 Mice carrying a germline mutation of this CBP phosphorylation site (S436A) demonstrate resistance to the hypoglycemic effect of both insulin and metformin.
5241 20813181 The serum insulin in PPE fed diabetic rats at the dose of 250 mg/kg b.w. was not different from those which had received glibenclamide, and this dose was significantly (p<0.05) more effective than PPE at the doses of 500 and 1000 mg/kg b.w. while PPE increased HDL and decreased TC, TG, LDL, BUN and ALP in the diabetic rats.
5242 21325104 Visfatin and adiponectin are produced by adipose tissue and have opposite effects on insulin resistance.
5243 21356520 Treatment with the incretin hormone glucagon-like peptide-1 (GLP-1) potentiates insulin secretion and improves metabolic control in humans with T2DM.
5244 21356520 Here we show that these incretin-stimulated pathways converge at the level of snapin, and that PKA-dependent phosphorylation of snapin increases interaction among insulin secretory vesicle-associated proteins, thereby potentiating glucose-stimulated insulin secretion (GSIS).
5245 21115832 Here, we identify 9cRA in mouse pancreas by liquid chromatography/tandem mass spectrometry (LC/MS/MS), and show that 9cRA decreases with feeding and after glucose dosing and varies inversely with serum insulin. 9cRA reduces glucose-stimulated insulin secretion (GSIS) in mouse islets and in the rat ?-cell line 832/13 within 15 min by reducing glucose transporter type 2 (Glut2) and glucokinase (GK) activities. 9cRA also reduces Pdx-1 and HNF4? mRNA expression, ?8- and 80-fold, respectively: defects in Pdx-1 or HNF4? cause maturity onset diabetes of the young (MODY4 and 1, respectively), as does a defective GK gene (MODY2).
5246 21205219 In response to CCT diet, a decrease in serum insulin, ?-amylase activity, hepatic glycogen, pancreatic calcium with a concomitant increase in serum glucose, lipid profile (except high-density lipoprotein cholesterol (HDL-C)), pancreatic nitrite and lipid peroxidation and the size of adipocytes along with macrophages infiltration were observed.
5247 21463618 Furthermore, SKLB102 elevated the serum level of adiponectin, reduced the serum level of leptin and prevented insulin resistance.
5248 19456151 Islet amyloid polypeptide (IAPP or amylin) is a 37-residue peptide hormone associated with glucose metabolism that is cosecreted with insulin by beta-cells in the pancreas.
5249 20559724 Nitric oxide (NO), synthesized from LS: -arginine by the enzyme endothelial nitric oxide synthase (eNOS), is a potent vasodilator and has been implicated in mediating insulin-induced uptake and metabolism of glucose in skeletal muscle.
5250 21315740 MTII treatment significantly reduced hepatic expression levels of genes encoding lipid biosynthetic enzymes, stearoyl-CoA desaturase 1 (SCD1), glycerol-3-phosphate acyltransferase 1 (GPAT1), acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), and DGAT2 mRNA without significant changes in serum insulin levels, homeostasis model-assessment of insulin resistance (HOMA-IR) and glucose tolerance in STZ-induced diabetic mice.
5251 21424113 Abnormal secretion of adipocytokines promotes atherosclerosis, diabetes and insulin resistance, and is mainly induced by adipocyte hypertrophy.
5252 21447485 However, inhibition of the conversion of PA to lysophosphatidylcholine (LPC) by calcium-independent phospholipase A? (iPLA?) inhibitors, such as bromoenol lactone (BEL) or palmitoyl trifluoromethyl ketone (PACOCF?), prevented insulin resistance by PA. iPLA? inhibitors or iPLA? small interfering RNA (siRNA) attenuated JNK or IRS-1 Ser307 phosphorylation by PA.
5253 20335584 The polymorphisms C-482T and T-455C in APOC3 are associated with nonalcoholic fatty liver disease and insulin resistance.
5254 20817212 Glucokinase regulates insulin secretion via phosphorylation of glucose.
5255 20332197 These studies provide new evidence that targeting IL-1beta in vivo could improve insulin sensitivity and lead to beta-cell sparing.
5256 20811152 These findings indicate that in adult mouse ? cells, Pcif1 limits Pdx1 protein accumulation and thus the expression of insulin and other gene targets important in the maintenance of ? cell mass and function.
5257 21354306 Insulin and insulin-like growth factor-1 (IGF-1) receptor signaling inhibits glucose-induced caspase-3 activation and apoptotic cell death.
5258 21431099 We have moved from a situation of only having two choices, insulin and sulfonylureas, to a position of myriad choices from 11 categories of medications (insulin, sulfonylureas, biguanides, ?-glucosidase inhibitors, gliptins (dipeptidyl peptidase 4 [DPP IV] inhibitors), bromocriptine, glucagon-like peptide analogues, thiazolidinediones, glinides, amylin analogues and bile acid sequestrants.
5259 21539509 The existing evidence suggests ghrelin primarily inhibits insulin release from the pancreas and we highlight an important mechanism involving AMPK-UCP2 ATP-stimulated potassium channels and intracellular calcium regulation.
5260 21181202 Downregulation of resistin and leptin gene expression after bariatric surgery may play a role in normalizing obesity-associated insulin resistance.
5261 19139117 The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade is an important component of the insulin signaling in normal tissues leading to glucose uptake and homeostasis and for cell survival signaling in cancer cells.
5262 21127832 We investigated associations of allelic variations in the WFS1 gene with insulin secretion and risk of type 2 diabetes in a general population prospective study.
5263 21153532 The Pro12 allele of PPARG2 seems to impair insulin's antilipolytic effect, leading to high NEFA release in the fasting state and IR.
5264 21153532 In addition, the type 2 diabetes risk alleles of KCNJ11 and HHEX, which are known to impair insulin secretion, were associated with increased hepatic insulin sensitivity.
5265 21164503 Under baseline diet conditions, RBP4 was associated with decreased disposition index (D(i)) (? = -2.4% (-4.5%; -0.2%), P = 0.04) and increased basal hepatic glucose production rate (HGP) (? = 0.02 mg kg(-1) min(-1) (0.002; 0.04), P = 0.03), but not associated with peripheral glucose disposal rate or hepatic insulin resistance index.
5266 21164503 In conclusion, plasma RBP4 in young men associates with components of the metabolic syndrome, but is not determined by birth weight and seems not to be involved in short-term high-fat diet-induced insulin resistance.
5267 21508227 Hypothalamic expression of TXNIP is induced by acute nutrient excess and in mouse models of obesity and diabetes, and downregulation of mediobasal hypothalamic TXNIP expression prevents diet-induced obesity and insulin resistance.
5268 21608432 We evaluated the effect of low doses of insulin (1 U/kg/day) and selenium (180 microg/kg/day) in combination on general physiological parameters, and on PI3K and GLUT4 levels in skeletal muscle of streptozotocin (STZ)-induced diabetic rats.
5269 21611153 Minor allele carriers at rs3962158 from DNAJB1 had increased fasting insulin (discovery cohort P?=?0.003), increased HOMA-IR (discovery cohort P?=?0.006; replication cohort P?=?0.036), and increased HOMA-%B (discovery cohort P?=?0.004).
5270 21611153 Carriers of haplotype 2 at DNAJB1 also had increased fasting insulin, HOMA-IR, and HOMA-%B.
5271 20869198 Adiponectin has been proposed as an important regulator of glucose metabolism influencing obesity and insulin resistance, which are important risk factors for the outcome of critically ill patients.
5272 21389141 Supposedly leptin modulates osteocalcin bioactivity, which in turn stimulates insulin and adiponectin secretion, and ?-cell proliferation.
5273 21389141 Linear regression models were used to test independent associations of adiponectin, osteocalcin, and leptin with the indices of insulin resistance and secretion.
5274 21389141 Both adiponectin and osteocalcin were negatively associated with insulin resistance.
5275 21389141 Structural equation modeling revealed a direct inverse association of leptin with osteocalcin; a direct positive association of osteocalcin with adiponectin; and an inverse relationship of osteocalcin with insulin resistance and adiponectin with insulin resistance and secretion, which is cumulatively consistent with the hypothesized model.
5276 21410335 We conducted a systematic review of randomized controlled trials (RCTs) that evaluated the effectiveness of insulin regimens with insulin analogs to reach the glycosylated hemoglobin (HbA1c) target of <7% in patients with type 2 diabetes.
5277 21411544 Insulin infusion significantly suppressed the expression of APP, presenilin-1, presenilin-2, and glycogen synthase kinase-3? in peripheral blood mononuclear cells.
5278 21411544 Insulin infusion also caused significant parallel reductions in nuclear factor-?B binding activity and plasma concentrations of serum amyloid A and intercellular adhesion molecule-1.
5279 21411544 A low dose infusion of insulin suppresses APP, presenilin-1, presenilin-2, and glycogen synthase kinase-3?, key proteins involved in the pathogenesis of Alzheimer's disease, in parallel with exerting its other antiinflammatory effects.
5280 21467195 Peripheral administration of a specific neurokinin-1 receptor (NK-1R) antagonist to mice leads to reduced weight gain and circulating levels of insulin and leptin after high-fat diet (HFD).
5281 21467195 Here, we assessed the contribution of substance P (SP) and NK-1R in diet-induced obesity using NK-1R deficient [knockout (KO)] mice and extended our previous findings to show the effects of SP-NK-1R interactions on adipose tissue-associated insulin signaling and glucose metabolic responses.
5282 21488802 Reduction of the glycemic load by acarbose decreased fasting levels of proinsulin but had no effect on adiponectin and whole-body insulin sensitivity as well as biomarkers reflecting inflammation.
5283 21574956 The age-related central resistance to leptin and insulin does not reduce their inhibitory effects on the activity of NPY and AgRP neurons.
5284 21106280 In streptozotocin-diabetic rats, we hypothesized that insulin negatively modulates liver SIRT1 and activates AMPK-inhibited lipogenic mediators leading to triglyceride accumulation.
5285 21106280 Compared to INS- (P < 0.05), INS+ had low liver SIRT1 with low AMPK activating phosphorylation, low inactivating phosphorylation of its lipogenic target acetyl-CoA carboxylase and high tissue triglycerides.
5286 21106280 Insulin replacement downregulates SIRT1 and AMPK activation in vivo in streptozotocin-diabetic rat liver, likely contributing to insulin-induced liver triglyceride accumulation.
5287 18710472 Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis.
5288 8613527 We have shown previously that chronic exposure of HIT-T15 cells to supraphysiologic glucose concentrations causes decreased insulin gene transcription and decreased binding activities of two beta-cell specific transcription factors, STF-1 and the RIPE3b1 activator, and have suggested that these events may provide a mechanism for glucose toxicity on beta-cell function.
5289 8613527 Mutation of the RIPE3b1 binding site almost completely abolished insulin gene transcription as well as binding activity.
5290 8866550 In contrast to the insulin gene, however, neither the synergistic effect of the Pan1 expression on the IPF1-induced promoter activation nor the glucose responsiveness of the activity was observed for the GK gene promoter.
5291 9000703 Reduction of GLUT2 is associated with loss of glucose-induced insulin secretion in genetic and chemical diabetes and in transplanted islets exposed to chronic hyperglycemia.
5292 9000703 These data suggest that 1) the loss of GLUT2 protein associated with hyperglycemia is at least partially explained by reduced levels of the GLUT2 gene transcripts; 2) the reduction of beta-cell insulin content during chronic hyperglycemia may not be completely due to degranulation (reduced levels of gene transcripts may play a role); and 3) the reduction in the transcription factor IDX-1 raises the possibility that dysregulation of transcription factors may contribute to the abnormal beta-cell function found in states of chronic hyperglycemia.
5293 9022089 In a second study, inclusion of somatostatin in the media-containing 11.1 mM glucose inhibited insulin secretion; however, despite this protection against beta cell exhaustion, dramatic decreases in insulin gene expression, STF-1 and RIPE-3b1 binding, and insulin gene promoter activity still occurred.
5294 9453241 The transcriptional control of the gene in beta-cells involves at least two islet-specific DNA-binding proteins, GTIIa and PDX-1, which also transactivates the insulin, somatostatin and glucokinase genes.
5295 9460079 Notably, three MODY genes encode transcription factors implicated in the regulation of insulin gene transcription: hepatocyte nuclear factors 1 alpha and 4 alpha, and islet duodenum homeobox-1 (IDX-1, also known as IPF-1).
5296 9604866 Furthermore, decreases in insulin gene transcription and binding activity of two essential beta-cell transcription factors, somatostatin transcription factor-1 (STF-1; also known as GSTF, IDX-1, IPF-1, PDX-1, and GSF) and RIPE-3b1 activator, are associated with this glucotoxic effect.
5297 9604866 Since the STF-1, but not the RIPE-3b1 activator, gene has been cloned, we examined its restorative effects on insulin gene promoter activity after reconstitution with STF-1 cDNA.
5298 9604866 Compared with basal levels, we observed a trend toward an increase in insulin promoter activity in intermediate passage cells with STF-1 transfection (1.43-fold) that became a significant increase when E2-5 was cotransfected (1.78-fold).
5299 9604866 In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity.
5300 9604866 Control studies in glucotoxic betaTC-6 cells deficient in RIPE-3b1 activator but not STF-1 did not demonstrate an increase in insulin promoter activity after STF-1 transfection.
5301 9616224 Impaired functions of the transactivating factors islet duodenum homeobox-1 (IDX-1) and RIPE3b-binding proteins have been implicated in the pathological downregulation of insulin gene transcription by high glucose levels in pancreatic beta cell lines in vitro, and, similarly, the exposure of pancreatic islets to fatty acids decreases IDX-1 expression.
5302 9616224 Our findings indicate that the differential dysregulation of both IDX-1 and C/EBPbeta, in response to sustained hyperglycemia or hyperlipidemia, may be involved in the impairment of insulin gene expression during the manifestation of diabetes mellitus.
5303 9637677 These mice develop diabetes with age, and we show that IPF1/PDX1 is required for maintaining the beta cell identity by positively regulating insulin and islet amyloid polypeptide expression and by repressing glucagon expression.
5304 9649577 This circumstance suggests that the mechanism of diabetes in these individuals may be due not only to reduced gene dosage, but also to a dominant negative inhibition of transcription of the insulin gene and other beta cell-specific genes regulated by the mutant IPF-1.
5305 10078550 Islet duodenal homeobox 1 (IDX-1/PF-1/STF-1/PDX-1), a homeodomain protein that transactivates the insulin promoter, has been shown by targeted gene ablation to be required for pancreatic development.
5306 10342809 We also demonstrated that high glucose dramatically lowered the binding activity of pancreatic duodenal homeobox 1 (the glucose-sensitive transcription factor), whereas the transcription factor rat insulin promoter element 3b1 activator was less influenced and insulin enhancer factor 1 remained unaffected.
5307 10499550 The results of electrophoretic mobility shift experiments showed that PDX-1 protein binding to the Al element of the rat insulin II promoter was also increased 2 h post treatment with GLP-1.
5308 10545531 Functional transactivation assays of these IPF-1 mutant isoforms in a beta-pancreatic tumor cell line transfected with a transcriptional reporter and IPF-1 expression plasmids demonstrate a significant inhibition of basal insulin promoter activity (stronger with the InsCCG243 mutant).
5309 10567373 In addition, they exhibit impaired expression of the homeodomain transcription factor PDX1, which is a key component of the signaling pathway linking nutrient metabolism to the regulation of insulin gene expression.
5310 10567702 PDX-1 has been suggested to be involved in the glucose-dependent regulation of insulin gene transcription.
5311 10580420 To investigate if this sensitivity represents an acquired trait during beta-cell maturation, we used two in vitro cultured cell systems: 1) a pluripotent glucagon-positive pre-beta-cell phenotype (NHI-glu) that, after in vivo passage, matures into an insulin-producing beta-cell phenotype (NHI-ins) and 2) a glucagonoma cell-type (AN-glu) that, after stable transfection with pancreatic duodenal homeobox factor-1 (PDX-1), acquires the ability to produce insulin (AN-ins).
5312 10720084 We conclude that variants in IPF-1 are not a common cause of MODY or late-onset type 2 diabetes in the Caucasian population, and that in terms of insulin transcription both the N76 and the T140 mutations are likely to represent functionally normal IPF-1 variants with no direct role in the pathogenesis of MODY or late-onset type 2 diabetes mellitus.
5313 10868963 These effects are partially mediated through the activity of a homeodomain transcription factor, PDX-1, which binds to four sites within the human insulin gene promoter.
5314 10868963 However, in NES2Y cells stably transfected with PDX-1 (NES-PDX-1), glucose exhibited a marked stimulatory effect on both the insulin promoter (5+/-0.2-fold, n = 6) and insulin mRNA levels (4.8+/-0.5-fold, n = 4).
5315 10868963 These results demonstrate that glucose modulation of insulin mRNA levels is dependent on the activity of PDX-1 and that these effects are independent of changes in intracellular Ca2+ concentrations.
5316 10905482 Here, we show that the insulinotropic hormone glucagon-like peptide (GLP)-1, which is produced by the intestine, enhances the pancreatic expression of the homeodomain transcription factor IDX-1 that is critical for pancreas development and the transcriptional regulation of the insulin gene.
5317 10905482 Concomitantly, GLP-1 administered to diabetic mice stimulates insulin secretion and effectively lowers their blood sugar levels.
5318 10905482 Thus, in addition to stimulating insulin secretion, GLP-1 stimulates the expression of the transcription factor IDX-1 while stimulating beta-cell neogenesis and may thereby be an effective treatment for diabetes.
5319 10909415 We demonstrated that PDX-1 is sufficient to activate the endogenous, otherwise silent, mouse insulin 1 and 2 and pro-insulin convertase gene expression in liver.
5320 11108273 Here, we show that continuous infusion of glucagon-like peptide-1 (7-36) (GLP-1; an insulinotropic agent), to young and old animals, had effects on the beta-cell of the pancreas other than simply on the insulin secretory apparatus.
5321 11237222 GLP-1 increases both the number of cells secreting insulin and the amount secreted per cell.
5322 11237222 This response to GLP-1 is retained even in the beta cell of the old (i.e., 22-month), glucose-intolerant Wistar rat, which exhibits a normal, first-phase insulin response to glucose following an acute bolus of GLP-1.
5323 11237222 Preincubation with GLP-1 (24 hours) potentiates glucose- and GLP-1-dependent insulin secretion and increases insulin content in the insulinoma cells.
5324 11237222 Treatment of old Wistar rats for 48 hours with GLP-1 leads to normalization of the insulin response and an increase in islet insulin content and mRNA levels of GLUT 2 and glucokinase.
5325 11237222 Administration of GLP-1 to old rats leads to pancreatic cell proliferation, insulin-positive clusters, and an increase in beta-cell mass.
5326 11316746 It mediates increases in glucose-stimulated insulin secretion by activating adenylyl cyclase and elevating free cytosolic calcium levels in the beta-cell.
5327 11316746 Furthermore, forskolin, (which stimulates adenylyl cyclase and insulin secretion), and 8-Bromo-cAMP, (an analog of cAMP which also stimulates insulin secretion), mimicked the effects of GLP-1 on PDX-1.
5328 11457885 Mutations in the homeodomain transcription factor IDX-1, a critical regulator of pancreas development and insulin gene transcription, confer a strong predisposition to the development of diabetes mellitus in humans.
5329 11457885 Doxycycline-induced impairment of IDX-1 expression reduced activation of the Insulin promoter but activated the Idx-1 promoter, suggesting that pancreatic beta cells regulate IDX-1 transcription to maintain IDX-1 levels within a narrow range.
5330 11574405 Glucose and insulin regulate PDX-1 by way of a signaling pathway involving phosphatidylinositol 3-kinase (PI 3-kinase) and SAPK2/p38.
5331 11574405 Glucose- and insulin-stimulated translocation of PDX-1 to the nucleoplasm was inhibited by wortmannin and SB 203580, indicating that a pathway involving PI 3-kinase and SAPK2/p38 was involved; translocation was unaffected by PD 098959 and rapamycin, suggesting that neither mitogen-activated protein kinase nor p70(s6k) were involved.
5332 11574405 These results demonstrated that PDX-1 shuttles between the nuclear periphery and nucleoplasm in response to changes in glucose and insulin concentrations and that these events are dependent on PI 3-kinase, SAPK2/p38, and a nuclear phosphatase(s).
5333 11697865 We observed an increased mRNA expression of insulin, proendocrine gene neurogenin 3, and beta-cell transcription factor Pdx1 when the cells were grown on bovine collagen I gels.
5334 12011435 Here, we report cloning of the human mafA (hMafA) and demonstrate that it can specifically bind the insulin enhancer element RIPE3b and activate insulin-gene expression.
5335 12099699 Pdx-1 is also able to bind and activate transcription from the A3 element of the human insulin gene promoter in yeast.
5336 12124776 Differentiation to insulin-producing cells was also seen when Capan-1 cells were transfected with pdx-1, with 80% of these cells expressing insulin 3 days after transfection.
5337 12145164 When the PDX-1(+) IEC-6 cells were kept in vitro, treatment with betacellulin could also confer insulin gene expression to them.
5338 12150938 Glucose-regulated transcription of the insulin gene is in part mediated via the homeobox transcription factor PDX-1.
5339 12503852 Glucose, the main physiological regulator of insulin secretion, also regulates insulin gene transcription through PDX-1.
5340 12697734 Mice with 50% Pdx1, a homeobox gene critical for pancreatic development, had worsening glucose tolerance with age and reduced insulin release in response to glucose, KCl, and arginine from the perfused pancreas.
5341 12697734 Surprisingly, insulin secretion in perifusion or static incubation experiments in response to glucose and other secretagogues was similar in islets isolated from Pdx1(+/-) mice compared with Pdx1(+/+) littermate controls.
5342 12697734 These results suggest that an increase in apoptosis, with abnormal regulation of islet number and beta cell mass, represents a key mechanism whereby partial PDX1 deficiency leads to an organ-level defect in insulin secretion and diabetes.
5343 12756298 We explored whether fetal human progenitor liver cells (FH) could be induced to differentiate into insulin-producing cells after expression of the pancreatic duodenal homeobox 1 (Pdx1) gene, which is a key regulator of pancreatic development and insulin expression in beta cells.
5344 12756298 Immortalized FH cells expressing Pdx1 activated multiple beta-cell genes, produced and stored considerable amounts of insulin, and released insulin in a regulated manner in response to glucose.
5345 12869553 We have also demonstrated the expression of upstream genes of Pdx-1, such as HNF3beta and HNF1alpha, as well as its downstream genes, including insulin, Glut2, and Nkx6.1, to be well preserved.
5346 15047618 The results showed that pdx-1 expression clearly enhanced the expression of the insulin 2, somatostatin, Kir6.2, glucokinase, neurogenin3, p48, Pax6, PC2, and HNF6 genes in the resulting differentiated cells.
5347 15047618 Thus, exogenous expression of pdx-1 should provide a promising approach for efficiently producing insulin-secreting cells from human ES cells for future therapeutic use in diabetic patients.
5348 15121856 PCIF1 is expressed in adult pancreatic insulin-producing beta cells, and overexpression of PCIF1 inhibits the rat insulin 1 and rat insulin 2 promoters in the MIN6 insulinoma beta cell line.
5349 15126294 Under diabetic conditions, JNK is activated by oxidative stress and involved in the suppression of insulin gene expression.
5350 15180990 Although chromatin immunoprecipitation assays show that both Pax-6 and Pdx-1 bind to the IGRP promoter within intact cells, in contrast to the critical role of these factors in beta cell-specific insulin gene expression, IGRP gene transcription appears to require Pax-6 but not Pdx-1.
5351 15331541 In vitro treatment of embryonic pancreata with dexamethasone, a glucocorticoid agonist, induced a decrease of insulin-expressing cell numbers and a doubling of acinar cell area, indicating that glucocorticoids favored acinar differentiation; in line with this, expression of Pdx-1, Pax-6, and Nkx6.1 was downregulated, whereas the mRNA levels of Ptf1-p48 and Hes-1 were increased.
5352 15514704 As a possible mechanism underlying the phenomena, expression of pancreatic and duodenal homeobox factor-1 (PDX-1), an important transcription factor for the insulin gene, was more clearly visible in the nuclei of islet cells after the antioxidant treatment.
5353 15561947 We do not however find any expression of the late-stage genes (Pax4, Pax6, Isl-1, and MafA) related to beta-cell development, and the cells do not secrete insulin upon the glucose challenge.
5354 15664997 MafA, a recently isolated pancreatic beta-cell-specific transcription factor, is a potent activator of insulin gene transcription.
5355 15664997 In this study, we show that MafA overexpression, together with PDX-1 (pancreatic and duodenal homeobox factor-1) and NeuroD, markedly increases insulin gene expression in the liver.
5356 15677506 Similarly, Ex-4 failed to increase levels of plasma insulin, pancreatic insulin content, and pancreatic insulin mRNA transcripts in beta-cell(Pdx1-/-) mice.
5357 15677506 Moreover, Ex-4 increased the levels of insulin and amylin mRNA transcripts and augmented glucose-stimulated insulin secretion in islets from beta-cell(Pdx1+/+) mice but not in beta-cell(Pdx1-/-) islets.
5358 15677507 To investigate effects of this synthetic lipid regulator on insulin secretion, we generated transgenic mice overexpressing nuclear SREBP-1c under the insulin promoter. beta-Cell-specific expression of SREBP-1c caused reduction in islet mass and impaired glucose-stimulated insulin secretion and was associated with accumulation of triglycerides, suppression of pancreas duodenal homeobox-1, and upregulation of uncoupling protein 2 gene expression.
5359 15769977 Gastrin, alone or in combination with EGF, but not EGF alone, increased the expression of pancreatic and duodenal homeobox factor-1 as well as insulin and C peptide in the cytokeratin 19-positive duct cells.
5360 15769977 Also, EGF plus gastrin significantly increased beta-cells and insulin content in human islets implanted in immunodeficient nonobese diabetic-severe combined immune deficiency mice as well as insulin secretory responses of the human islet grafts to glucose challenge.
5361 15793239 In this study, we showed that a modified form of the pancreatic and duodenal homeobox factor 1 (PDX-1) carrying the VP16 transcriptional activation domain (PDX-1/VP16) markedly increases insulin biosynthesis and induces various pancreas-related factors in the liver, especially in the presence of NeuroD or neurogenin 3 (Ngn3).
5362 15793239 Thus PDX-1/VP16 expression, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance.
5363 15896300 We previously reported that exogenous PDX-1 protein can permeate cells and induce insulin gene expression in progenitor cells.
5364 15899968 PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner.
5365 15935394 The release of insulin, the expression of preproinsulin (PPI), glucose transporter2 (GLUT2) and pancreatic duodenal homeobox-1 (PDX-1), and levels of intracellular free Ca++([Ca++]i) were measured in rat pancreatic islets treated with or without high concentrations of FFA (0.1 and 1.0 mM oleic acid) for 24 h.
5366 16055439 Insulin gene expression is regulated by pancreatic beta cell-specific factors, PDX-1 and BETA2/E47.
5367 16443759 Although bone marrow cells expressing GFP under the ubiquitously expressed beta-actin promoter efficiently engrafted the pancreas of normal and hyperglycemic mice, virtually all expressed CD45 and Mac-1/Gr-1, demonstrating that they adopt a hematopoietic rather than beta-cell fate, a finding further substantiated by the complete absence of GFP(+) cells expressing insulin and the beta-cell transcription factors pancreatic duodenal homeobox factor-1 and homeodomain protein.
5368 16469158 The aim of the present study was to determine, in weanling Wistar rats, the effect of a maternal high-fat diet (HFD) during defined periods of gestation and lactation, on body weight, circulating glucose and insulin concentrations, and the expression of GLUT-2, GK and Pdx-1.
5369 16504534 A more promising gene therapy approach has been to express pancreatic endocrine developmental factors, such as PDX-1, NeuroD/BETA2 and Neurogenin 3, to promote differentiation of non-endocrine cells towards a beta cell or islet phenotype, enabling these cells to synthesize and secrete insulin in a glucose-regulated manner.
5370 16543365 We found that overexpression of Egr-1 in clonal (INS-1) beta-cells increased transcriptional activation of the rat insulin I promoter.
5371 16543365 In contrast, reductions in Egr-1 expression levels or function with the introduction of either small interfering RNA targeted to Egr-1 (siEgr-1) or a dominant-negative form of Egr-1 decreased insulin promoter activation, and siEgr-1 suppressed insulin gene expression.
5372 16543365 Egr-1 did not directly interact with insulin promoter sequences, and mutagenesis of a potential G box recognition sequence for Egr-1 did not impair the Egr-1 responsiveness of the insulin promoter, suggesting that regulation of insulin gene expression by Egr-1 is probably mediated through additional transcription factors.
5373 16543365 Notably, augmenting Egr-1 expression levels in insulin-producing cells increased the mRNA and protein expression levels of pancreas duodenum homeobox-1 (PDX-1), a major transcriptional regulator of glucose-responsive activation of the insulin gene.
5374 16543365 Increasing Egr-1 expression levels enhanced PDX-1 binding to insulin promoter sequences, whereas mutagenesis of PDX-1-binding sites reduced the capacity of Egr-1 to activate the insulin promoter.
5375 16543365 We propose that changes in Egr-1 expression levels in response to extracellular signals, including glucose, can regulate PDX-1 expression and insulin production in pancreatic beta-cells.
5376 16837621 Induction of WT HNF1beta also inhibited the insulin secretory response to nutrient stimuli, membrane depolarisation or activation of protein kinases A and C and this correlated with a significant decrease in pancrease-duodenum homeobox-1 protein levels.
5377 16921545 However, when hepatocytes were allowed to reaggregate for 4 and 6 days in hydrophobic plates after transduction with NeuroD1, further increases of insulin 2 mRNA were found along with induction of PDX-1, IAPP, NeuroD1, Ngn3, Pax 4, Isl-1, PC1, PC2 and islet glucokinase.
5378 16921545 Ngn 3 and Pax 4 had effects similar to NeuroD1, but did not increase insulin 2 mRNA as much as NeuroD1.
5379 16936190 Islets exposed to sirolimus for 24 h in culture displayed significantly diminished glucose-stimulated insulin release, coinciding with decreased pancreas duodenum homeobox-1 and GLUT2 expression in cultured islets.
5380 16936209 RNA of Pdx-1, Glut-2, and Gck was detectable by RT-PCR in whole thymus but not in the clones, suggesting thymic proinsulin expression is Pdx-1 independent and that Pdx-1, Glut-2, and Gck are likely expressed in the thymus as antigens, not as regulatory molecules.
5381 16996478 In addition, to examine the functional role of Rho/Rho-kinase in beta-cells, we evaluated the effect of Rho-kinase inhibitors on insulin biosynthesis.
5382 16996478 Northern blot analysis showed that insulin mRNA levels were markedly increased by Rho-kinase inhibitors, Y-27632 and fasudil, in beta-cell-derived HIT-T15 cells.
5383 17095531 It has been shown that abnormal O-GlcNAc modification (O-GlcNAcylation) of proteins is one of the causes of insulin resistance and diabetic complications.
5384 17095531 PUGNAc, an inhibitor of O-GlcNAcase, induced an elevation of O-GlcNAc level and a decrease of glucose-stimulated insulin secretion in isolated islets.
5385 17130469 We provide evidence that continued expression of Hnf6 impairs GSIS by altering insulin granule biosynthesis, resulting in a reduced response to secretagogues.
5386 17150967 Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia.
5387 17158802 Insulin treatment was associated with the nuclear localization of Pdx1 and the prosurvival effects of insulin were largely absent in islets 50% deficient in Pdx1, providing direct evidence that Pdx1 is a signaling target of insulin.
5388 17158802 Bridge-1, a Pdx1-binding partner and regulator of beta-cell survival, was increased significantly at low insulin doses.
5389 17158802 Together, these data suggest that insulin can act as a master regulator of islet survival by regulating Pdx1.
5390 17226789 The differentiated PDX-1+ hMSCs expressed multiple islet-cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C-peptide in a weak glucose-regulated manner.
5391 17259388 Inhibition of endogenous SHP gene expression by small interfering RNA partially restored high-glucose-induced suppression of the insulin gene.
5392 17259388 Adenovirus-mediated overexpression of SHP in INS-1 cells impaired glucose-stimulated insulin secretion as well as insulin gene expression.
5393 17259388 SHP downregulates insulin gene expression via two mechanisms: by downregulating PDX-1 and MafA gene expression and by inhibiting p300-mediated pancreatic duodenal homeobox factor 1-and BETA2-dependent transcriptional activity from the insulin promoter.
5394 17299998 Infection with the adenovirus expressing PDX-1, Ngn3, NeuroD, or Pax4 induced the insulin gene expression.
5395 17299998 NeuroD was the most effective inducer of insulin expression in primary duct cells.
5396 17449132 MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription.
5397 17449132 Furthermore, MafA markedly enhances insulin gene promoter activity and ameliorates glucose tolerance in diabetic mice, especially in the presence of PDX-1 and NeuroD.
5398 17467845 In conclusion, with increasing age, insulin secretory function of islets deteriorates accompanied with a decrease in expression of beta cell-specific genes including PDX-1.
5399 17627512 In mature beta-cells, PDX-1 transactivates the insulin gene and other genes involved in glucose sensing and metabolism, such as GLUT2 and glucokinase.
5400 17627512 MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription.
5401 17706592 Insulin promoter assay showed that Pdx1 highly activates insulin promoter when combined with Ngn3.
5402 17709883 The molecular mechanisms responsible for the glucose toxic effect on beta cell function involves disappearance of two important regulators of insulin promoter activity, PDX-1 and MafA.
5403 17785922 It is produced exclusively by pancreatic islet beta-cells. beta-cell-enriched transcription factors, such as Pdx1 and Beta2, have dual roles in the activation of the insulin gene promoter establishing beta-cell-specific insulin expression, and in the regulation of beta-cell differentiation.
5404 17785922 MafA acts synergistically with Pdx1 and Beta2 to activate the insulin gene promoter, and mice with a targeted deletion of mafA develop age-dependent diabetes.
5405 17785922 This review summarizes recent progress in determining the functions and roles of MafA in the regulation of insulin gene transcription in beta-cells.
5406 17900743 Thus, our study demonstrated that pdx-1 is not essential for insulin gene expression, at least in cells differentiated from this population of nestin-expression enriched ES cells, and suggested that the insulin-producing cells derived from ES cells may be different from the pancreatic beta cells in terms of their lineage.
5407 17941991 Expression of either human insulin or the beta cell specific transcription factors PDX-1, NeuroD1 and MafA in the Hepa1-6 cell line or primary liver cells via adenoviral gene transfer, results in production and secretion of insulin.
5408 17949261 The progression of hyperglycemia and the reduction of body weight gain and insulin content of the db/db mouse were significantly suppressed by the TRX expression.
5409 17991758 Prolonged exposure of isolated islets of Langerhans to elevated levels of fatty acids, in the presence of high glucose, impairs insulin gene expression via a transcriptional mechanism involving nuclear exclusion of pancreas-duodenum homeobox-1 (Pdx-1) and loss of MafA expression.
5410 17991758 This was associated with reduced Pdx-1 binding to the endogenous insulin promoter, and an increased proportion of Pdx-1 localized in the cytoplasm versus the nucleus.
5411 18360684 PDX-1 binds to the promoter of insulin, glucose transporter 2, and glucokinase and regulates their expression.
5412 18360684 By protein-protein interaction, PDX-1 acts in concert with other transcription factors or coactivators at the level of the insulin promoter.
5413 18508668 MafA is a recently isolated beta-cell-specific transcription factor and functions as a potent activator of insulin gene transcription.
5414 19062254 Interestingly, immunohistochemistry demonstrated that, the islets from MSC-treated rats expressed high levels of PDX-1 and that these cells were also positive for insulin staining.
5415 19155609 Using this device, we showed that IHG induced more serious impairment in INS-1 cells than did SHG, and adiponectin partially rescued INS-1 cells from glucotoxicity-induced apoptosis, dysfunction and reduction of insulin gene expression.
5416 19168505 In DM control IHBECs started to express some endocrine progenitor genes (Neurog3, NeuroD, Nkx6.1, and Pdx-1) but lacked insulin gene (Ins) mRNA.
5417 19168505 Transduced expression of PDX-1, NEUROD or PDX-1/VP16 led to expression of not only INS but also GLUT2 and prohormone convertase 1 and 2.
5418 19213841 When fed either a low-fat/high-sucrose or high-fat/high-sucrose diet, GPR39(-/-) mice had increased fed glucose levels and showed decreased serum insulin levels during an oral glucose tolerance test in the face of unchanged insulin tolerance.
5419 19213841 Pancreas morphology and glucose-stimulated insulin secretion in isolated islets from wild-type and GPR39(-/-) mice were comparable, suggesting that GPR39 is not required for pancreas development or ex vivo insulin secretion.
5420 19213841 Taken together, our data indicate that GPR39 is required for the increased insulin secretion in vivo under conditions of increased demand, i.e. on development of age-dependent and diet-induced insulin resistance.
5421 19393272 Indeed, PDX-1 binding to the A3 element and NeuroD binding to the E1 element are crucial for insulin gene transcription.
5422 19393272 Recently, C1 element-binding transcription factor was identified as MafA, which is a basic-leucine zipper transcription factor and functions as a potent transactivator for the insulin gene.
5423 19393272 Furthermore, MafA overexpression, together with PDX-1 and NeuroD, markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells.
5424 19604517 Gestational high-fat programming impairs insulin release and reduces Pdx-1 and GK immunoreactivity.
5425 19689288 MafA, PDX-1 and NeuroD directly bind to the insulin gene promoter and function as very important transcription factors in pancreatic beta-cell differentiation and mature beta-cell function.
5426 19689288 The combination of MafA, PDX-1 and NeuroD markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells.
5427 19757377 While stable expression of Pdx1 in ASCs did not induce the pancreatic phenotype in vitro in our experiment, the transplanted stem cells became engrafted in the pancreas, wherein they expressed insulin and C-peptide, which is a marker of insulin-producing cells.
5428 19785038 We explored this possibility by determining whether ectopic expression of transcription factors known to induce transcription of this gene in beta cells, pancreatic and duodenal homeobox factor 1 (Pdx1), V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa), and neurogenic differentiation 1 (Neurod1), would activate INS gene expression in long-term hIPC cultures.
5429 19785038 Coexpression of all three transcription factors had little effect on INS mRNA levels but unexpectedly increased GCG mRNA at least 100,000-fold.
5430 19785038 In contrast to the endogenous promoter, an exogenous rat INS promoter was activated by expression of Pdx1 and Mafa in hIPCs.
5431 19785038 Lastly, ChIP assays show that exogenously expressed Pdx1 and Mafa bind at very low levels to the INS promoter and at 20- to 25-fold higher levels to the GCG promoter in hIPCs.
5432 19855005 Here, we find that Pdx1 is required for compensatory beta cell mass expansion in response to diet-induced insulin resistance through its roles in promoting beta cell survival and compensatory hypertrophy.
5433 19855005 These findings suggest that Pdx1 deficiency leads to a failure of beta cell compensation for insulin resistance at least in part by impairing critical functions of the ER.
5434 19901909 Pancreatic duodenal homeobox 1 (Pdx1) protein is a key transcription factor involved in the regulation of insulin gene expression that is expressed at high levels in the beta-cells of the pancreatic islets.
5435 20349222 Surprisingly, XBP1s overexpression impaired glucose-stimulated insulin secretion and increased beta cell apoptosis, whereas it protected fibroblasts against cell death induced by ER-stress. mRNA expression of Pdx1 and Mafa was inhibited in cells overproducing XBP1s, leading to decreased insulin expression.
5436 20349222 XBP1s knockdown partially restored cytokine/ER-stress-driven insulin and Pdx1 inhibition but had no effect on cytokine-induced ER-stress and apoptosis.
5437 20349222 Prolonged XBP1s production hampers beta cell function via inhibition of insulin, Pdx1 and Mafa expression, eventually leading to beta cell apoptosis.
5438 20360006 Measurement of the 50 most highly regulated genes by quantitative PCR did not reveal a single gene regulated uniquely via the IR or IGF1R using cells expressing exclusively IGF-1 or insulin receptors.
5439 20360006 Thus, IR and IGF1R act as identical portals to the regulation of gene expression, with differences between insulin and IGF-1 effects due to a modulation of the amplitude of the signal created by the specific ligand-receptor interaction.
5440 21285283 These results suggest that with increasing age autocrine effects of resistin in fat tissue may predispose to diabetes in part by impairing insulin action in adipose tissue.
5441 19833886 Actin stabilization prevented nephrin trafficking as well as nephrin-positive effect on insulin release.
5442 20080388 Processed insulin is recognized by alphabeta T cells, which mediate diabetes in non-obese diabetic (NOD) mice.
5443 20299464 However, middle-aged mice fed a high-fat diet were more susceptible to the development of insulin resistance-a condition that could be prevented by limiting skeletal muscle fatty acid transport and excessive lipid accumulation in middle-aged CD36 KO mice.
5444 20299467 Conditional overexpression of E2F1 in mice resulted in a twofold increase of beta-cell proliferation and a 70% increase of pancreatic insulin content, but did not increase beta-cell mass.
5445 20299470 Age- and BMI-adjusted FASN concentrations were significantly increased in association with obesity-induced insulin resistance in two independent cohorts.
5446 20299470 Improved insulin sensitivity induced by therapeutic strategies that decreased fat mass (diet induced, surgery induced, or physical training) all led to decreased FASN levels in blood (P values between 0.02 and 0.04).
5447 20299473 Insulin and contraction increase TBC1D1 phosphorylation on phospho-Akt substrate motifs (PASs), but the function of TBC1D1 in muscle is not known.
5448 20299473 Surprisingly, expression of TBC1D1 mutated to Ala on four conserved Akt and/or AMP-activated protein kinase predicted phosphorylation sites (4P) had no effect on insulin-stimulated glucose transport.
5449 20299475 The mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) pathway is a critical signaling component in the development of obesity-linked insulin resistance and operates a nutrient-sensing negative feedback loop toward the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway.
5450 20299475 The robust induction of the gluconeogenic program in liver of rapamycin-treated rats underlies the development of severe glucose intolerance even in the face of preserved hepatic insulin signaling to Akt and despite a modest reduction in adiposity.
5451 20299477 As increased adipogenesis and insulin sensitivity suggested aspects of augmented peroxisome proliferator-activated receptor-gamma (PPARgamma) response, we investigated Txnip's regulation of PPARgamma function; manipulation of Txnip expression directly regulated PPARgamma expression and activity.
5452 20299477 Txnip deletion promotes adiposity in the face of high-fat caloric excess; however, loss of this alpha-arrestin protein simultaneously enhances insulin responsiveness in fat and skeletal muscle, revealing Txnip as a novel mediator of insulin resistance and a regulator of adipogenesis.
5453 20332343 Thiazolidinedione activation (72 h) of this pathway in normal mouse islets caused a threefold increase of GIP-R protein and a doubling of insulin secretion to 16.7 mmol/l glucose/10 nmol/l GIP.
5454 20354156 We conclude that LKB1 and AMPK play distinct roles in the control of insulin secretion and that the timing of LKB1 deletion, and/or its loss from extrapancreatic sites, influences the final impact on beta-cell function.
5455 20354158 In both hypothalamic cell lines, inflammation was induced by prototypical inflammatory mediators LPS and TNFalpha, as judged by induction of IkappaBalpha (3- to 5-fold) and IL-6 (3- to 7-fold) mRNA and p-IkappaBalpha protein, and TNFalpha pretreatment reduced insulin-mediated p-Akt activation by 30% (P < 0.05).
5456 20393162 Additionally, given that AMPK-activating drugs are widely prescribed for their insulin-sensitizing effects, we sought to determine whether 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR)-stimulated AMPK activation could prevent or reverse the deleterious effects of lipid on insulin signaling.
5457 20393162 We found that a 1-h palmitate incubation in lean myotubes reduced (P < 0.05) insulin-stimulated phosphoprotein kinase B (Akt), Akt substrate 160 (AS160), and inhibitory factor kappaBalpha (IkappaBalpha) mass, all of which were prevented with AICAR inclusion.
5458 20415685 Insulin sensitizers, including pioglitazone and rosiglitazone, and lipid-lowering agents, including statins and fibrates, also upregulate adiponectin and ameliorate liver histology.
5459 21464041 Higher insulin was also associated with an increased risk for cirrhosis diagnosed by ultrasonography and elevated alanine aminotransferase.
5460 19662359 The results showed that in G1, G2 and G3 groups, insulin secretion was enhanced with the increase of glucose concentration, and the NF-kappaB expression was also increased (P<0.05), but Bax activity, Cyt C release and apoptosis rate showed no significant difference among them.
5461 21288303 However, little is known about the regulation of Sirt1 and mir-9 levels in pancreatic ?-cells, particularly during glucose-dependent insulin secretion.
5462 21453786 In addition, in conditions of insulin resistance, i.e., preceding the onset of type 2 diabetes, the phosphatidylinositol (PI) 3-kinase (PI3K)/Akt pathway is selectively inhibited, while the mitogen activated protein (MAP)-kinase pathway remains largely unaffected, thus allowing compensatory hyperinsulinemia to elicit pro-atherogenic events in vascular smooth muscle and endothelial cells, including increased cell proliferation, and the expression of plasminogen activator inhibitor-1, as well as of proinflammatory cytokines and endothelial adhesion molecules.
5463 21549160 GLP-1(28-36)amide inhibited weight gain, accumulation of liver triglycerides, and improved insulin sensitivity by attenuating the development of fasting hyperglycemia and hyperinsulinemia in mice fed VHFD.
5464 18789716 OPG levels significantly correlate with insulin, insulin resistance, CRP, and TNF-alpha.
5465 15774581 Here, we report, for the first time, to our knowledge, the characterization of KLF11 as a glucose-inducible regulator of the insulin gene.
5466 15774581 A combination of random oligonucleotide binding, EMSA, luciferase reporter, and chromatin immunoprecipitation assays shows that KLF11 binds to the insulin promoter and regulates its activity in beta cells.
5467 17130506 Glycosphingolipid inhibitors augmented insulin-stimulated p70 S6kinase activity in the presence of inhibitory concentrations of high glucose or glucosamine.
5468 21226708 Association with adipokines favours the concept that AHSG is involved in atherosclerosis more likely through metabolic pathways (insulin resistance, obesity and adipocyte dysfunction) than by inflammation in patients with post-myocardial infarction.
5469 21264801 Furthermore we examined the association of apelin serum levels with insulin sensitivity/resistance and body fat distribution as probably dependent cardiovascular risk factors.
5470 21264801 Furthermore, neither parameters of insulin sensitivity like insulin sensitivity index (ISI), nor fat distribution like BMI, grade of adiposity, total adipose tissue or VAT were associated with apelin serum levels.
5471 21389296 Glucagon-like peptide-1 agonists are an attractive choice for patients in whom promotion of weight loss is a major consideration and the glycated hemoglobin level is moderately elevated (<8.0%) (ie, insulin is not required).
5472 21073393 MCP-1 was positively correlated with homeostasis model assessment of insulin resistance, homocysteine, and mean pulse wave velocity, but IL-8 was not.
5473 21497640 The pongamol-induced increase in GLUT4 translocation was completely abolished by wortmannin, and pongamol significantly potentiated insulin-mediated phosphorylation of AKT (Ser-473).
5474 21519236 Both cross-sectional and longitudinal studies support osteocalcin as an active regulator of carbohydrate metabolism in humans, being the muscular load of physical activity one of the possible links between the osteoblast and the insulin axis.
5475 18840364 We conclude that SirT1 gain of function primes the organism for metabolic adaptation to insulin resistance, increasing hepatic insulin sensitivity and decreasing whole-body energy requirements.
5476 20938440 Treatment of adipocytes and hSkMC with PEDF induced insulin resistance in adipocytes, skeletal and smooth muscle cells at the level of insulin-stimulated Akt phosphorylation, which was dose dependent and more prominent in adipocytes.
5477 20938440 PEDF is one of the most abundant adipokines and its secretion is inversely regulated by insulin and hypoxia.
5478 20938440 PEDF induces insulin resistance in adipocytes and hSkMC and leads to inflammatory signaling in hSMC.
5479 20938443 Polymorphisms in the gene encoding adiponectin receptor 1 (AdipoR1) are associated with insulin resistance, fatty liver, increased risk for type 2 diabetes and cardiovascular disease.
5480 21289260 The staining of AQP9 in the plasma membrane of adipocytes was reinforced by insulin, whereas isoproterenol induced the translocation of AQP3 and AQP7 from the lipid droplets to the plasma membrane.
5481 21289260 Insulin up-regulated all AQP, whereas leptin up-regulated AQP3 and down-regulated AQP7 and AQP9 in adipocytes and hepatocytes.
5482 21306933 Glycaemic control with insulin reduces ADPN in T2D patients in the short-term, but was ineffective in T1D.
5483 21616080 The formation of hIAPP amyloid plaques near islet cells has been linked to the death of insulin-secreting ?-cells in humans and the progression of type II diabetes.
5484 21620811 Serum BDNF is decreased in young nonobese women with low insulin sensitivity.
5485 21671169 To further examine the related mechanisms, this study was designed to evaluate the association of SUMO4 Met55Val polymorphism with insulin resistance and ? cell function in newly diagnosed type 2 diabetic patients in a Chinese population.
5486 17983584 Here we used reciprocal adoptive transfer experiments to determine whether JNK1 in myeloid cells, such as macrophages, also contributes to insulin resistance and central adiposity.
5487 20221699 MicroRNA375 (miR375) is highly expressed in pancreatic islets of humans and mice and regulates insulin secretion in isolated pancreatic cells.
5488 20221699 The expression of myotrophin (Mtpn) decreased and insulin secretion was reduced in Nit-1 cells transfected with pAAV-miR375.
5489 20221699 We verified that miR375 reduced glucose-induced insulin secretion by down-regulating the expression of Mtpn in Nit-1 cells in vitro, suggesting that miR375 has potential therapeutic applications in type II diabetes.
5490 20233941 Apelin, an adipocyte-secreted factor upregulated by insulin, is increased in adipose tissue (AT) and plasma with obesity.
5491 20233941 However, the regulation of apelin and APJ (apelin receptor) expression in skeletal muscle in relation to insulin resistance or type 2 diabetes is not known.
5492 21265823 In both HF rats and mice, NNC61-5920 treatment attenuated hepatic insulin resistance and decreased expression of stearoyl-CoA desaturase 1, fatty acid translocase protein CD36 and lipoprotein lipase in liver.
5493 21356512 In this issue of Cell Metabolism, Kubota et al. (2011) show that deletion of IRS-2 in endothelial cells in mice causes impaired transcapillary insulin transport, decreased insulin-stimulated glucose uptake in muscle, and mild glucose intolerance.
5494 21356519 Moreover, restoration of insulin-induced eNOS phosphorylation in endothelial cells completely reverses the reduction in capillary recruitment and insulin delivery in tissue-specific knockout mice lacking Irs2 in endothelial cells and fed a high-fat diet.
5495 21478228 In this study, we treated diabetic apolipoprotein E-deficient (apoE-/-) mice with insulin for 20 weeks and studied the effect of insulin treatment on intimal lesion size and matrix metalloproteinase (MMP) 9 expression known to be involved in plaque destabilization.
5496 21478228 Results showed that insulin treatment, which effectively reduced plasma glucose level in diabetic mice, attenuated diabetes-increased intimal lesion size and significantly inhibited diabetes-increased MMP9 expression, but had no effect on tissue inhibitor of metalloproteinase 1 in atherosclerotic plaques.
5497 21478228 Furthermore, we observed that insulin treatment did not reduce diabetes-increased macrophage content but inhibited interleukin 6 expression, a stimulator for MMP expression.
5498 21555344 In this issue of Journal of Endocrinology, Schuyler et al. show that intimal lesions in atherosclerosis-prone diabetic apoE(-/-) mice are reduced by insulin treatment.
5499 21674027 DLBS3233 was also found to enhance the expression of genes associated with increased insulin signaling and sensitivity, such as peroxisome proliferator-activated receptor gamma, phosphatidylinositol-3 kinase, Akt, and glucose transporter 4.
5500 20179357 Studies using RIP-Cre:Vegf(fl/fl) mice revealed that defects in the normal vascular structure are associated with abnormal insulin secretion and concluded that the islet vascular system is essential for normal insulin secretion into the blood stream.
5501 20376319 Omental, but not subcutaneous adipocyte size, correlated with the degree of insulin resistance as measured by HOMA-IR (r = 0.73, p<0.0005), as well as other metabolic parameters including triglyceride/HDL-cholesterol ratio and HbA1c.
5502 20383279 Angiotensin II (Ang II) plays a major role in the pathogenesis of insulin resistance and diabetes by inhibiting insulin's metabolic and potentiating its trophic effects.
5503 20383279 We found Ang II to block insulin-dependent GLUT4 translocation in L6 myotubes in an NO- and O(2)(*-)-dependent fashion suggesting the involvement of peroxynitrite.
5504 20383279 Taken together, our data show that Ang II inhibits insulin-mediated GLUT4 translocation in this skeletal muscle model through at least two pathways: first through the transient activation of ERK1/2 which inhibit IRS-1/2 and second through a direct inhibitory nitration of Akt.
5505 21309058 FGF21 exposure increased basal and insulin-stimulated glucose uptake in human myotubes, coincident with increased glucose transporter 1 mRNA, and enhanced glucose transporter 1 abundance at the plasma membrane.
5506 21309058 In isolated extensor digitorum longus muscle, FGF21 potentiated insulin-stimulated glucose transport, without altering phosphorylation of Akt or AMP-activated protein kinase.
5507 21321189 Here, we demonstrate that adenovirus-mediated overexpression of SIRT1 in the liver of diet-induced insulin-resistant low-density lipoprotein receptor-deficient mice and of genetically obese ob/ob mice attenuates hepatic steatosis and ameliorates systemic insulin resistance.
5508 21321189 Conversely, SIRT1-deficient mouse embryonic fibroblasts challenged with tunicamycin exhibited markedly increased mTORC1 activity and impaired ER homeostasi and insulin signaling.
5509 15855318 Inducible nitric oxide synthase (iNOS) has been implicated in many human diseases associated with inflammation. iNOS deficiency was shown to prevent high-fat diet-induced insulin resistance in skeletal muscle but not in the liver.
5510 21205117 GLP-1 exerts its glucose-regulatory action via stimulation of insulin secretion and glucagon suppression by a glucose-dependent way, as well as by weight loss via inhibition of gastric emptying and reduction of appetite and food intake.
5511 21498783 We hypothesized that an imbalance of ATGL relative to HSL (expression or activity) may contribute to DAG accumulation and insulin resistance.
5512 21498783 We show that selective HSL inhibition induces DAG accumulation and insulin resistance.
5513 21498783 Altogether, the data indicate that altered ATGL and HSL expression in skeletal muscle could promote DAG accumulation and disrupt insulin signaling and action.
5514 21515851 To determine whether insulin reverses gestational diabetes mellitus (GDM)-reduced expression and activity of human equilibrative nucleoside transporters 1 (hENT1) in human umbilical vein endothelium cells (HUVECs).
5515 21515851 Insulin effect was assayed on hENT1 expression (protein, mRNA, SLC29A1 promoter activity) and activity (initial rates of adenosine transport) as well as endothelial nitric oxide (NO) synthase activity (serine(1177) phosphorylation, l-citrulline formation).
5516 21087777 The purpose of this study was to determine if changes in body mass index (BMI) and insulin sensitivity influence circulating OPG in healthy subjects.
5517 21087777 Both OPG and adiponectin were negatively correlated with body weight, BMI, waist circumference, and fasting plasma insulin while being positively correlated with insulin sensitivity (P < .05).
5518 21087777 In contrast to patients with type 2 diabetes mellitus, circulating OPG is lower in obese, but otherwise healthy subjects and is positively correlated with indices of insulin sensitivity.
5519 21129759 In mixed adipocyte populations and adipose tissue pieces from young, but not old, rats, lipolysis inhibition by above antilipolytic stimuli, but not by insulin, was dependent on the function of Gce1-harboring adiposomes.
5520 21178385 These results suggest that inhibition of S6K1 for up to 4 weeks may be therapeutically relevant to induce insulin sensitization and attenuate weight gain with low risk for serious toxicity.
5521 21543335 Recently, Glis3 has been linked to both type I and type II diabetes and shown to positively regulate insulin gene expression.
5522 21543335 We further showed that SUFU is able to inhibit the activation of the insulin promoter by Glis3 but not the activation by a Glis3 mutant deficient in its ability to bind SUFU, suggesting that the inhibitory effect is dependent on the interaction between the two proteins.
5523 21682153 Genetic testing identified the presence of the de nova V59M and E322K activating mutations in the KCNJ11 gene encoding the sulphonylurea/potassium channel (Kir6.2 subunit) of the insulin beta cell.
5524 21686137 Also, induced significantly higher activities of hepatic G6Pase and glycogen phosphorylase compared with controls, while give significant lowered serum insulin, C-peptide level and renal catalase activity.
5525 17915193 Insulin treatment may attenuate the impairment of Bcrp expression and function induced by diabetes.
5526 17915193 All results gave a conclusion that STZ-induced DM may induce the impairment of function and expression of Bcrp in brain cortex, and lower levels of insulin may mainly contribute to Bcrp dysfunction in brain.
5527 20308781 These results suggest that statin use may modulate insulin levels for individuals without an APOE epsilon4 allele.
5528 21263402 These data reflect an association of analyzed PPARG and LPIN1 gene polymorphisms with values of insulin, HDL, LDL and total cholesterol witch indicates an important role of these genes in lipid metabolism and pathogenesis of type 2 diabetes and metabolic syndrome.
5529 21646544 Pharmacological and genetic interventions revealed that insulin regulates GLUT4 and FoxO1 through the PI3-kinase isoform p110?, although FoxO1 showed higher sensitivity to p110? activity than GLUT4.
5530 21646544 Transient down-regulation and overexpression of Akt isoforms in adipocytes demonstrated that insulin-activated PI3-kinase signals to GLUT4 primarily through Akt2 kinase, whereas Akt1 and Akt2 signal to FoxO1.
5531 21646544 We propose that the lower threshold of insulin activity for FoxO1's nuclear exclusion is in part due to its regulation by both Akt isoforms.
5532 21694775 We then assessed the effects of an insulin sensitizer, rosiglitazone (RSG), in treatment naļve T2DM subjects, on circulating visfatin levels.
5533 21694775 Our findings showed that visfatin was reduced post-RSG treatment [vs. pre-treatment (*p<0.05)] accompanied by a reduction in HOMA-IR**, thus implicating a role for insulin in visfatin regulation.
5534 21694775 Following insulin (Ins) and RSG treatment, our in vitro findings highlighted that insulin (100 nM), alone, upregulated visfatin protein expression whereas, in combination with RSG (10 nM), it reduced visfatin*, IKK?** and p-JNK1/2*.
5535 21694775 These data highlight visfatin's regulation by insulin and RSG, potentially acting through NF-?B and JNK mechanisms, with only rh IL-6 modestly affecting visfatin regulation.
5536 21694920 Adiponectin potentiates insulin in its post-receptor signaling resulting in glucose oxidation in mitochondria.
5537 21694920 Fatty acid accumulation and resistin inhibit insulin and adiponectin.
5538 18418065 In particular, we highlight the emerging role for Raf-1 kinase in autocrine insulin signaling and beta-cell fate decisions.
5539 21602511 Overactivity of the Forkhead transcription factor FoxO1 promotes diabetic hyperglycemia, dyslipidemia, and acute-phase response, whereas suppression of FoxO1 activity by insulin may alleviate diabetes.
5540 21602511 Treatment with MEDICA analog resulted in total body sensitization to insulin, suppression of lipopolysaccharide-induced hCRP and interleukin-6-induced acute phase reactants and robust decrease in FoxO1 transcriptional activity and in coactivation of STAT3.
5541 21602512 Cholecystokinin (CCK) is released in response to lipid intake and stimulates insulin secretion.
5542 21602512 We hypothesized that CCK deficiency would alter the regulation of insulin secretion and glucose homeostasis.
5543 21602512 CCK is involved in regulating insulin secretion and glucose tolerance in mice eating an HFD.
5544 21617181 It has been suggested that interleukin (IL)-6 is one of the mediators linking obesity-derived chronic inflammation with insulin resistance through activation of STAT3, with subsequent upregulation of suppressor of cytokine signaling 3 (SOCS3).
5545 19375553 Adiponectin correlated with insulin levels and Homeostasis Model of Assessment 2 (r=-0.653, P=.04 and r=-0.674, P=.032, respectively) in the patients who underwent Roux-en-Y at 24 months.
5546 21487310 Intranasal delivery of insulin was associated with greater preservation of the phosphatidylinositol 3-kinase signaling pathway involving Akt, cyclic AMP response element binding protein,and glycogen synthase kinase 3? but did not alter extracellular signal-regulated kinase, mitogen-activated protein kinase/extracellular signal-regulated kinase, or c-Jun amino-terminal kinase.
5547 21515669 The hemodynamic actions of adiponectin may be an important aspect of its insulin-sensitizing ability by regulating access of insulin and glucose to myocytes.
5548 21515669 Imbalance in the relationship between adiponectin and ET-1 in obesity may contribute to the development of insulin resistance and cardiovascular disease.
5549 21644225 The present study suggests that the rs6025422 polymorphism in (BMP7) gene may be associated with diabetes mellitus and insulin resistance in Uygur men.
5550 21717410 Leptin plays a crucial role in the maintenance of body weight and glucose homeostasis hrough central and peripheral pathways, including regulation of insulin secretion by pancreatic b cells.
5551 21717410 Recent data provides convincing evidence that leptin has beneficial effects on glucose homeostasis in mouse models of insulin-deficient type 1 diabetes mellitus.
5552 18219478 Transgenic mice overexpressing a constitutively active form of human GSK3beta (S9A) under the control of the rat insulin promoter (RIP-GSK3betaCA) were created.
5553 21507882 For Obrq2a1, genetic and functional studies collectively identified the solute receptor Slc35b4 as a regulator of obesity, insulin resistance, and gluconeogenesis.
5554 21620903 In ob/ob islets the insulinotropic peptides glucagon, GLP-1 and GIP suppressed NOS activities and amplified glucose-stimulated insulin release.
5555 21620903 Islets from ob/ob mice existing in a hyperglycemic in vivo milieu maintain elevated insulin secretion and protection from glucotoxicity through a general suppression of islet NOS activities achieved by leptin deficiency, high CO production and insulinotropic cyclic-AMP-generating hormones.
5556 21628999 Glucose and insulin did not affect CPD or CPE expression in an ?-cell line.
5557 21628999 Furthermore, insulin treatment altered the CPD sub-cellular localization, which was distinct from CPE.
5558 20382687 Linear regression was used to explore the association between adiponectin levels and measures of obesity, lipids, and insulin resistance as measured by homeostasis model assessment.
5559 20382687 Circulating adiponectin is significantly associated with measures of obesity, serum lipids, and insulin resistance in this study of West African populations.
5560 21298325 The aims of this study are to address if insulin is anti-inflammatory and attenuates IL-6-induced inflammation in the human hepatoma cell line HepG2 and if this involves signal transducer and activator of transcription 3 (STAT3) signal transduction.
5561 21298325 It was found that insulin significantly reduced IL-6-induced gene transcription of serum amyloid 1 (SAA1), serum amyloid 2 (SAA2), haptoglobin, orosomucoid, and plasmin activator inhibitor-1 (PAI-1).
5562 21298325 However, the authors did not find any evidence that insulin inhibited IL-6 signal transduction, i.e., no effect of insulin was detected on STAT3 phosphorylation or its translocation to cell nucleus.
5563 21298325 Further analysis revealed that insulin regulates nuclear localization of FOXO1, which is an important co-activator for STAT3 mediated transcription.
5564 21332446 GLP-1, GIP, Liraglutide, N-AcGIP(Lys(37)Myr) (N-acetylGIP with myristic acid conjugated at Lys(37)), a simple combination of both peptides and a Lira-AcGIP preparation [overnight preparation of Liraglutide and N-AcGIP(Lys(37)Myr)] were incubated with DPP-IV (dipeptidyl peptidase-IV) to assess peptide stability, and BRIN-BD11 cells were used to evaluate cAMP production and insulin secretion.
5565 21589925 Plasma amylin levels are elevated in individuals with obesity and insulin resistance.
5566 21589925 Monocyte chemoattractant protein-1 (MCP-1, CCL2) is involved in insulin resistance of obesity and type 2 diabetes.
5567 21589925 Amylin upregulation by MCP-1 may contribute to elevation of plasma amylin in obesity and insulin resistance.
5568 21589939 IRS-1 serine phosphorylation was increased (1.30±0.09 vs. 0.22±0.03 OD units, P<0.005) while insulin-stimulated tyrosine phosphorylation decreased (10.97±0.95 vs. 0.89±0.50 OD units, P<0.005).
5569 21589939 This is the first report demonstrating that insulin resistance in non-obese, normoglycemic subjects is associated with activation of the JNK pathway related to increased IMCL and higher total body and abdominal adipose stores.
5570 21590629 Patients with MODY 3 were changed from insulin to repaglinide, those with MODY 2 were recommended discontinuing insulin treatment.
5571 21623861 Insulin signalling in the osteoblasts increases bone formation and resorption as well as the release of undercarboxylated osteocalcin.
5572 21654750 We demonstrate that caveolin-1 is upregulated upon miR-103/107 inactivation in adipocytes and that this is concomitant with stabilization of the insulin receptor, enhanced insulin signalling, decreased adipocyte size and enhanced insulin-stimulated glucose uptake.
5573 21731668 After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum.
5574 21508147 In both the normal-glucose and prediabetes groups, carboxylated osteocalcin was associated with insulin sensitivity (? = 0.26, 0.47, respectively, both P < 0.02).
5575 21510839 Intravenous GLP-1 has been shown to increase insulin secretion in response to elevated glucose levels and offers therapeutic benefit for patients with type 2 diabetes.
5576 21525163 Cultured primary human trophoblasts, exposed to insulin (10 nM) and/or fatty acids mix (1200 ?M) in the absence or presence of an fatty acid binding protein 4 (FABP4) inhibitor or after small interfering RNA-mediated knockdown of FABP4.
5577 9930932 CD38 is involved in the formation of cyclic ADP-ribose and is essential for the glucose sensitivity of beta-cells for insulin secretion.
5578 9930938 CONCLUSION: PFK1-M-deficiency leads to a metabolic state typical for early NIDDM in homozygously affected humans, especially concerning insulin resistance and loss of first phase beta-cell insulin secretion, and may contribute to the manifestation of NIDDM in a subgroup of patients.
5579 11862322 In conclusion, the Arg972 (IRS-1) background produced a marked difference in insulin sensitivity between X/Ala and Pro/Pro (PPARgamma) which was not present in the whole population or against the Gly972 (IRS-1) background.
5580 12436346 It has been suggested that several agents, such as tumor necrosis factor alpha, could mediate their effects on insulin metabolism through modulating adiponectin secretion from adipocytes.
5581 15592805 The role of regulatory polymorphisms in determining susceptibility to a number of complex disease traits is discussed, including variation at the VNTR of INS, encoding insulin, in type 1 diabetes and polymorphism of CTLA4, encoding cytotoxic T lymphocyte antigen, in autoimmune disease.
5582 15821902 CDK4 is involved in the regulation of body weight, pancreatic beta-cell proliferation, insulin responsiveness, and diabetes pathogenesis.
5583 16897074 The aim of this study was to verify whether activation of fatty acid oxidation by PPARbeta agonists in human skeletal muscle cells prepared from type 2 diabetic patients could improve the reduced responses to insulin that characterized this cell model.
5584 16897074 Myotubes from type 2 diabetic patients displayed marked reduction in the effects of insulin on glycogen synthesis and on PKB phosphorylation.
5585 19083193 This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation.
5586 19083193 Taken together these data suggest that HSP70, by affecting ENPP1 expression, may be a novel mediator of altered insulin signaling.
5587 19809796 This study validates and confirms the association of IDE polymorphisms with T2DM risk in the prospective German cohort and provides novel evidence of influences of IDE genetic variants on insulin metabolism.
5588 17130464 Clinical insulin resistance is associated with decreased activation of phosphatidylinositol 3'-kinase (PI3K) and its downstream substrate protein kinase B (PKB)/Akt.
5589 17130464 In the present study, the effect of in vivo insulin action on phosphorylation of the PKB/Akt substrate 40 (PRAS40) was examined.
5590 17130464 In rat and mice, insulin stimulated PRAS40-Thr246 phosphorylation in skeletal and cardiac muscle, the liver, and adipose tissue in vivo.
5591 17130464 In cultured cell lines, insulin-mediated PRAS40 phosphorylation was prevented by the PI3K inhibitors wortmannin and LY294002.
5592 17130464 Phosphorylation of PRAS40 is increased by insulin in human, rat, and mouse insulin target tissues.
5593 20959720 Gut hormone ghrelin and adipokine adiponectin are both decreased in obesity and they share a potent effect on insulin sensitivity: both adiponectin and the combination of acylated (AG) and unacylated ghrelin (UAG) improve insulin sensitivity.
5594 21384500 Furthermore, risk alleles in TCF7L2 have been suggested to account for decreased conversion of proinsulin to insulin and decreased expression of GLP-1.
5595 21384500 Our data demonstrate that TCF7L2 variants are associated with an early age of onset of type 2 diabetes in Caucasians and affects the conversion of proinsulin to insulin.
5596 21478152 Resistin has been suggested to be involved in the development of diabetes and insulin resistance.
5597 21478152 Furthermore, resistin increased serine phosphorylation of insulin receptor substrate (IRS1) through the activation of the apoptosis signal-regulating kinase 1/c-Jun N-terminal Kinase (JNK) pathway, a module known to stimulate insulin resistance.
5598 21478152 These data demonstrate that resistin induces cardiac hypertrophy and myocardial insulin resistance, possibly via the AMPK/mTOR/p70(S6K) and apoptosis signal-regulating kinase 1/JNK/IRS1 pathways.
5599 21600725 The aims of this study were to compare total and high molecular weight (HMW) adiponectin and the ratio of HMW to total adiponectin (S(A)) between dogs and humans and to examine whether total or HMW adiponectin or both are associated with insulin resistance in naturally occurring obese dogs.
5600 21600725 Total adiponectin, HMW adiponectin, and S(A) were not associated with insulin sensitivity in dogs.
5601 21683066 Therefore, inhibition of PTP1B activity or down-regulation of its expression should ameliorate insulin and leptin resistance, and may hold therapeutic utility in type 2 diabetes mellitus and obesity control.
5602 20351753 We tested the hypothesis that the polymorphic residue at position 325 of ZnT-8 determines the susceptibility to cyclosporin A (CsA) suppression of insulin secretion.
5603 20351753 A reduced number of insulin granule fusion events accompanied the decrease in insulin secretion in CsA-treated cells expressing ZnT-8 R325; however, ZnT-8 W325-expressing cells exhibited resistance to the dampening of insulin granule fusion by CsA, and transported zinc ions into secretory vesicles more efficiently.
5604 20351753 These data suggest that the ZnT-8 W325 variant is protective against CsA-induced suppression of insulin secretion.
5605 20498699 Significantly, our results reveal that insulin signaling is normally regulated by IDE activity not only extracellularly but also within cells, supporting the longstanding view that IDE inhibitors could hold therapeutic value for the treatment of diabetes.
5606 20878500 At linear regression analyses, GGT was significantly correlated with admission glycemia (r = 0.172; p = 0.002), uric acid (r = 0.146; p = 0.011), insulin (r = 0.171; p = 0.002) and age (r = -0.129; p = 0.020).
5607 21602604 The aim of this study was to investigate the role of insulin in the regulation of breast cancer resistance protein (BCRP) function and expression using primary cultured rat brain microvessel endothelial cells (rBMECs) as an in vitro model of the blood brain barrier (BBB).
5608 21602604 Further results showed that insulin down-regulated the function and expression of BCRP in rBMECs in a concentration-dependent manner.
5609 21602604 These results indicate that insulin suppressed the function and expression of BCRPs in rBMEC primary cultures.
5610 21644917 Insulin also suppresses lipolysis by down-regulating the expression of the rate-limiting lipolytic enzyme, adipose triglyceride lipase or ATGL.
5611 16203173 Other studies have shown defects in insulin signaling possibly secondary to activation of Protein Kinase C resulting from the accumulation of active fatty acyl CoA's.
5612 16226915 Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1.
5613 16226915 Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling.
5614 16951716 Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components.
5615 16951721 Our preliminary studies found that the extracts of American ginseng inhibit UCP-2 expression which may contribute to the ability of ginseng protecting beta cell death and improving insulin synthesis.
5616 16951721 Therefore, we hypothesized that ginseng extracts suppress UCP-2 in the mitochondria of pancreatic beta cells, promoting insulin synthesis and anti-apoptosis (a programmed cell-death mechanism).
5617 16951721 We found that ginseng suppresses UCP-2, down-regulates caspase-9 while increasing ATP and insulin production/secretion and up-regulates Bcl-2, reducing apoptosis.
5618 16951721 These findings suggest that stimulation of insulin production and prevention of beta cell loss by American ginseng extracts can occur via the inhibition of mitochondrial UCP-2, resulting in increase in the ATP level and the anti-apoptotic factor Bcl-2, while down-regulation of pro-apoptotic factor caspase-9 occurs, lowering the occurrence of apoptosis, which support the hypothesis.
5619 18763075 In the present study, we investigate effect of amylin on the insulin sensitivity of rat skeletal muscle extensor digitorum longus (EDL) using in vitro intact muscle incubation in combination with metabolic radioactive labeling.
5620 18763075 We found that amylin significantly decreased the insulin-stimulated glucose incorporation into glycogen (p < 0.01) and produced a protein spot of approximately 20 ku in size.
5621 18763075 In conclusion, our results showed that in vitro amylin concomitantly evoked the production of ARP1 and caused insulin resistance in EDL muscle.
5622 19096709 Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in the regulation of insulin resistance and adipogenesis.
5623 19423844 Western blot analysis of extracts of Akita mice demonstrated that insulin treatment increased the expression of GIRK1, SREBP-1, and I(KAch) activity in atrial myocytes from these mice to levels in wild-type mice.
5624 19423844 Insulin treatment of cultured atrial myocytes stimulated GIRK1 expression 2.68+/-0.12-fold (P<0.01), which was reversed by overexpression of dominant negative SREBP-1.
5625 19423844 These results support a unique molecular mechanism for insulin regulation of GIRK1 expression and parasympathetic response via SREBP-1, which might play a role in the pathogenesis of DAN in response to insulin deficiency in the diabetic heart.
5626 19707284 The low risk of hypoglycemia, and beneficial or neutral effects on body weight, render GLP-1 agonists and DPP-4 inhibitors suitable alternatives to insulin secretagogues and insulin in overweight and elderly patients.
5627 19709445 Therefore, we found it of interest to investigate whether IL-8 is involved in the insulin action in human adipocytes.
5628 19709445 The IL-8 inhibited insulin-induced Akt phosphorylation.
5629 19709445 These data suggest that IL-8 is a main adipocytokine producing insulin resistance via the inhibition of insulin-induced Akt phosphorylation in adipocytes.
5630 20184722 Serum HER-2 concentrations were positively associated with BMI and waist circumference (both r = 0.18, p = 0.02), post-load glucose (r = 0.28, p = 0.001) and fasting triglycerides (r = 0.26, p = 0.001); and negatively associated with insulin sensitivity (r = -0.29, p = 0.002, n = 109).
5631 20184722 In different multivariate regression models, fasting triglycerides emerged as the factor that independently contributed to 10-11% of serum HER-2 variance.Serum HER-2 concentrations correlated significantly with fasting triglycerides and insulin sensitivity index in subjects from cohort 2.
5632 20431808 These 50 functional genes are responsible for diabetic nephropathy; of these 50, some of the genes which are more expressed and responsible are AGXT: Alanine-glyoxylate aminotransferase, RHOD: Ras homolog gene family, CAPN6: Calpain 6, EFNB2: Ephrin-B2, ANXA7: Annexin A7, PEG10: Paternally expressed 10, DPP4: Dipeptidyl-peptidase 4 (CD26, adenosine deaminase complexing protein 2), ENSA: Endosulfine alpha, IGFBP2: Insulin-like growth factor binding protein 2, 36kDa, CENPB: Centromere protein B, 80kDa, MLL3: Myeloid/lymphoid or mixed-lineage leukemia 3, BDNF: Brain-derived neurotrophic factor, EIF4A2: Eukaryotic translation initiation factor 4A, isoform 2, PPP2R1A: Protein phosphatase 2 (formerly 2A), regulatory subunit A, alpha isoform.
5633 20678967 Insulin resistance, but not the body mass index, was associated with increased macrophage infiltration in the omental adipose tissue, as was adipocyte size, in these morbidly obese subjects.
5634 21484150 GLUT4 gene expression was highly down-regulated in SIT-treated adipocytes, compared to insulin-treated adipocytes, which was up-regulated.
5635 11435467 To address whether these latter changes were caused by glucose toxicity, we treated muscle GLUT4 KO mice with phloridzin to prevent hyperglycemia and found that insulin-stimulated whole body and skeletal muscle glucose uptake were decreased substantially, whereas insulin-stimulated glucose uptake in adipose tissue and suppression of hepatic glucose production were normal after phloridzin treatment.
5636 17724080 Because adiposity affects insulin sensitivity, the extent to which PTP1B directly regulates glucose homeostasis has been unclear.
5637 17724080 Nevertheless, muscle-specific PTP1B(-/-) mice exhibit increased muscle glucose uptake, improved systemic insulin sensitivity, and enhanced glucose tolerance.
5638 18840786 FGF21 also reduced blood glucose, insulin, and lipid levels and reversed hepatic steatosis.
5639 18952837 Skeletal muscle triglyceride was 38% lower, and insulin-stimulated phosphorylated Akt (Ser473) was twofold greater in SMLPL(-/-) mice without changes in IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase activity.
5640 18952837 LPL deletion in skeletal muscle reduces lipid storage and increases insulin signaling in skeletal muscle without changes in body composition.
5641 19841069 These data demonstrate that JNK1 in muscle contributes to peripheral insulin resistance in response to diet-induced obesity.
5642 20444420 The increased insulin sensitivity in the VLCAD(-/-) mice were protected from diet-induced obesity and insulin resistance due to chronic activation of AMPK and PPARalpha, resulting in increased fatty acid oxidation and decreased intramyocellular and hepatocellular diacylglycerol content.
5643 21296137 PA-evoked inflammation impaired insulin signaling cascades and mSMS improved insulin signaling transduction by modification of Ser/Thr phosphorylation of IRS-1 and downstream Akt (T308), thereby improved insulin sensitivity in hepatocytes. mSMS also improved glucose intolerance induced by inflammatory cytokines in normoglycemic mice, which further demonstrated its modulation toward insulin sensitivity in vivo.
5644 21389182 The rs2953171 polymorphism at the CAPN10 gene locus may influence insulin sensitivity by interacting with the plasma fatty acid composition in subjects with MetS.
5645 21412813 In cultured hepatocytes, PANDER overexpression induced lipid deposition, increased FOXO1 expression, and suppressed insulin-stimulated Akt activation and FOXO1 inactivation.
5646 21412813 CONCLUSION: PANDER promotes lipogenesis and compromises insulin signaling in the liver by increasing FOXO1 activity.
5647 21722517 LPL is an interesting enzyme that contributes in a pronounced way to normal metabolism, including insulin action, body weight regulation, energy balance, and atherosclerosis.
5648 21760856 We evaluated the effects of insulin-induced improved glycaemic control on leptin, adiponectin, ghrelin, neuropeptide Y (NPY) levels and patient characteristics.
5649 21760856 In both genders, insulin therapy (Group A) was associated with significant (p = 0.003 to <0.001) increases in weight, body mass index and leptin levels and significant decreases in glucose, HbA(1c) and NPY levels.
5650 21760856 Changes in leptin, adiponectin and NPY levels may occur after insulin-induced improved glycaemic control.
5651 9621990 This study aimed at investigating whether serum angiogenin levels are elevated in children and adolescents (youngsters) with insulin-dependent diabetes mellitus and whether angiogenin levels are affected by duration and metabolic control of the disease.
5652 18431372 Pegvisomant, a recombinant growth-hormone-receptor antagonist, suppresses production of insulin-like growth factor I.
5653 11015588 Agouti but not insulin significantly increased leptin secretion, indicating that insulin enhances leptin synthesis but not secretion while Agouti increases both leptin synthesis and secretion.
5654 11015611 We further investigated the mechanism responsible for the agouti-induced FAS expression in these cells and demonstrated that both insulin (3-fold increase) and agouti (2-fold) increased FAS gene expression at the transcriptional level.
5655 11245612 We hypothesize that agouti increases adiposity and promotes insulin sensitivity by acting directly on adipocytes via PPAR-gamma.
5656 11359864 We proceeded to analyze whether insulin or leptin played the greater role in the regulation of AGRP using Zucker fa/fa rats.
5657 20338842 Results suggest increasing mitochondrial density while decreasing UCP activity may be an effective way to increase glucose-stimulated insulin secretion while decreasing oxidative stress.
5658 21754917 Additionally, Akt activation and neurite outgrowth in response to insulin were significantly decreased in DRG cultures from diabetic ob/ob mice.
5659 21754921 We aimed to investigate whether CNTO 530, a novel Epo receptor agonist, could affect glucose tolerance and insulin sensitivity.
5660 21555853 Here we have employed a rat insulin II promoter-driven (RIP-driven) Cre recombinase to disrupt the GH receptor in ? cells (?GHRKO). ?GHRKO mice fed a standard chow diet exhibited impaired glucose-stimulated insulin secretion but had no changes in ? cell mass.
5661 21576825 Mice with global or liver-specific inactivation of the Prkcd gene displayed increased hepatic insulin signaling and reduced expression of gluconeogenic and lipogenic enzymes.
5662 20128800 Thus, the effects of GLP-1 receptor stimulation are not based upon insulin replacement but an apparent repair of the pancreas.
5663 21274504 In addition to improving insulin resistance and preventing ?-cell inflammatory damage, there is evidence of genetic association between diabetes and histone deacetylases (HDACs); and HDAC inhibitors (HDACi) promote ?-cell development, proliferation, differentiation and function and positively affect late diabetic microvascular complications.
5664 21306745 The Asp299Gly polymorphism in TLR4 was associated with increased insulin, homeostasis model assessment of insulin resistance (P < .05), and homeostasis model assessment of ?-cell function (P < .05) and family history of diabetes (P = .0002).
5665 21306748 The purpose of this study was to clarify the association of the angiotensinogen gene (AGT) with insulin sensitivity using single nucleotide polymorphism (SNP) and haplotype analyses in a white cohort.
5666 21776823 Receptor inhibitor studies indicated that p53 activation was mediated through insulin receptor (IR), not insulin-like growth factor-1 receptor (IGF-IR).
5667 21779625 Uncoupling protein 2 (UCP2) is expressed in several tissues, and acts in the protection against oxidative stress; in the negative regulation of insulin secretion by beta cells, and in fatty acid metabolism.
5668 21779631 Previous studies have suggested that Retinol Binding Protein 4 (RPB4), a protein produced by the adipose tissue, is associated with insulin resistance (IR).
5669 21411097 Adiponectin levels were negatively correlated with insulin and HOMA in both boys and girls, and remained significant after adjustment for BMI z-score in girls.
5670 21428745 Transgenic deletion of scavenger receptor type B CD36 in rodents has suggested a pivotal role for CD36 in mediating inflammation, insulin resistance, and atherogenesis through transport of fatty acids and uptake of oxidized lipids, respectively.
5671 21428745 CD36 signaling pathways involving c-Jun N-terminal kinase (JNK) activation and Toll-like receptors have been implicated in the induction of insulin resistance.
5672 21501070 Higher concentrations of CRP appear to be associated with greater skeletal muscle AT infiltration, lower subcutaneous AT, hyperinsulinemia, and insulin resistance.
5673 21646388 Despite the reported role of SOCS1 in inhibiting insulin signaling, it is surprising that a SOCS1 polymorphism that increases SOCS1 promoter activity is associated with enhanced insulin sensitivity despite obesity.
5674 21646388 In the current study, we investigated the physiological role of myeloid and lymphoid cell SOCS1 in regulating inflammation and insulin sensitivity.
5675 21646388 The expression of SOCS1 in hematopoietic cells protects mice against systemic inflammation and hepatic insulin resistance potentially by inhibiting LPS and palmitate-induced TLR4 signaling in macrophages.
5676 21677282 Our objective was to investigate whether exogenous ET-1 affects glucose uptake in the forearm of individuals with insulin resistance and in cultured human skeletal muscle cells.
5677 21677282 ET-1 decreased insulin-stimulated Akt phosphorylation and increased phosphorylation of insulin receptor substrate-1 serine 636.
5678 21677282 ET-1 not only induces vascular dysfunction but also acutely impairs FGU in individuals with insulin resistance and in skeletal muscle cells from type 2 diabetic subjects.
5679 7983784 It is important to investigate variations or mutations in the hCaCN4 gene, causing insufficient insulin secretion, leading to NIDDM.
5680 9200953 This finding suggests that PPAR gamma contributes regulation of insulin action.
5681 9648485 Besides the deficiency of insulin and insulin-like growth factor-I, we demonstrated that sustained hyperglycemia alone causes suppression of osteoblast proliferation and its response to parathyroid hormone and 1 alpha, 25-dihydroxyvitamin D, Hyporesponse of osteoblast to 1 alpha, 25-dihydroxyvitamin D, was also confirmed in diabetic patients as reflected by a reduction in an incremental response of serum osteocalcin during 1 alpha, 25-dihydroxyvitamin D administration.
5682 10199130 Regarding mechanism of obesity-induced insulin resistance, the increased expression of Tumor necrosis factor alpha and abnormality in PTPase are postulated.
5683 10199138 In addition, we have reported that reactive oxygen intermediates, advanced glycation end products and insulin-like growth factor-1, also all, may participate in the pathogenesis of DR through their ability to increase VEGF production.
5684 18018580 AdipoR1 expression was increased approximately 2.5-fold in muscle tissues from insulin-deficient diabetic mice, but normalized with insulin administration.
5685 19202909 Increasing evidence indicates that altered secretion of adipocytokines such as adiponectin, tumor necrosis factor alpha, monocyte chemoattractant protein-1 and free fatty acids are contributing factors to insulin resistance in obese states.
5686 19348235 On the other hand, RAA system activates the insulin resistance by angiotensin II (Ang II) blocking effects of the intracellular signal transduction system of insulin, by oxidative stress and by reduction of adiponectin level, which effects are induced by Ang II.
5687 19783811 In this study, we investigated the effect of FXR activation by 6-ethyl-chenodeoxycholic acid, (6E-CDCA, 10 mg/kg) on insulin resistance and liver and muscle lipid metabolism in fa/fa rats and compared its activity with rosiglitazone (10 mg/kg) alone or in combination with 6E-CDCA (5 mg/kg each).
5688 19783811 FXR activation protected against body weight gain and liver and muscle fat deposition and reversed insulin resistance as assessed by insulin responsive substrate-1 phosphorylation on serine 312 in liver and muscles.
5689 20103703 The family of glycoprotein 130 (gp130) cytokines could influence insulin action.
5690 20103705 Moreover, neither the phosphorylation of insulin signaling intermediates nor expression of gluconeogenic enzymes were altered in the lipid-infused iNOS(-/-) mice compared with their saline-infused controls.
5691 20103705 These findings demonstrate that iNOS induction is a novel mechanism by which circulating lipids inhibit hepatic insulin action.
5692 20103705 Our results further suggest that iNOS may cause hepatic insulin resistance through tyrosine nitration of key insulin signaling proteins.
5693 20107106 While hepatic insulin resistance was similar in the fasting state, carriers of the minor G allele had lower hepatic glucose output (per-allele effect: -16%, P(add) = 0.004) during high physiological insulin infusion. rs361072 did not associate with insulin-stimulated peripheral glucose disposal despite a decreased muscle p85alpha:p110beta protein ratio (P(add) = 0.03) in G allele carriers.
5694 20107106 Our study suggests that the minor G allele of PIK3CB rs361072 associates with decreased muscle p85alpha:p110beta ratio and lower hepatic glucose production at high plasma insulin levels.
5695 20107108 Here, we studied OPN effects in obesity-induced inflammation and insulin resistance by targeting OPN action in vivo.
5696 20107108 Moreover, we report OPN as a novel negative regulator for the activation of hepatic signal transducer and activator of transcription 3 (STAT3), which is essential for glucose homeostasis and insulin sensitivity.
5697 20107108 These findings demonstrate that antibody-mediated neutralization of OPN action significantly reduces insulin resistance in obesity.
5698 20107108 OPN neutralization partially decreases obesity-associated inflammation in adipose tissue and liver and reverses signal transduction related to insulin resistance and glucose homeostasis.
5699 20107109 The aim of this study was to determine whether the type 2 diabetes-associated T-allele of transcription factor 7-like 2 (TCF7L2) rs7903146 associates with impaired insulin secretion to compensate for insulin resistance induced by bed rest.
5700 20158103 Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcription factor that has a central role in the regulation of insulin sensitivity and adipocyte differentiation.
5701 20350970 Moreover, these macrophage Ad-TG mice exhibit enhanced whole-body glucose tolerance and insulin sensitivity with reduced proinflammatory cytokines, MCP-1 and TNF-a (both in the serum and in the metabolic active macrophage), adipose tissue, and skeletal muscle under the high-fat diet condition.
5702 20446576 Since insulin regulates the eNOS activity through the phosphorylation by AKT, insulin resistance is one of major factors associating with the endothelial dysfunction in obesity and diabetes.
5703 20446595 GIP and GLP-1 potentiate glucose-induced insulin secretion by binding GIP receptor and GLP-1 receptor, respectively, on pancreatic beta-cell and increasing intracellular cAMP concentration (incretin effect).
5704 20446595 GIP and GLP-1 have not only pancreatic effect, such as potentiation of insulin secretion, but also many extrapancreatic effects.
5705 21595261 Incretin hormones, GLP-1 and GIP, contribute to whole body glucose homeostasis by modulating secretion of islet hormones, insulin, glucagon and somatostatin.
5706 21595261 Both GLP-1 and GIP stimulate insulin and somatostatin secretion.
5707 21595264 GIP and GLP-1 have not only pancreatic effect, such as potentiation of insulin secretion but also many extrapancreatic effects.
5708 21595271 Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide(GIP) function as incretin and stimulate glucose-mediated insulin production by pancreatic beta cells.
5709 21595282 GLP-1(7-36)NH2 is a major molecular form that stimulates insulin release, reduces food intake, and has a potential to promote beta-cell regeneration.
5710 21595282 Intranasal administration of GLP-1 increased its plasma level, stimulated postprandial insulin release, and suppressed glucagon release.
5711 21595285 Glucose-dependent insulinotropic polypeptide(GIP) has been known as a peptide hormone with the effects not only of the augmentation of glucose induced insulin secretion but of the fat accumulation in adipocytes, of the bone formation and of the modulation of brain function.
5712 21699724 After controlling for age and BMI, Ang-2 levels were associated with levels of sTie-2, diastolic blood pressure, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), creatinine, glomerular filtration rate (GFR), and gamma-glutamyl transferase (GGT) (all p < 0.02).
5713 21699724 Presence of diabetic macrovascular complications, polyneuropathy and insulin therapy were associated with higher Ang-2 levels (p < 0.05).
5714 21699724 Ang-2 is independently associated with levels of GGT while sTie-2 is independently associated with levels of HbA(1c), plasma insulin and HOMA-IR in type 2 diabetic subjects.
5715 21736747 Decreased adiponectin is associated with insulin resistance and predicts T2DM, and therefore may mediate this ethnic difference.
5716 21769255 Plasma ACTH did not increase with insulin loading.
5717 21321479 Cathepsin L also enhances insulin-induced glucose uptake into 3T3-L1 adipocytes, suggesting cathepsin L plays the roles in adipogenesis and glucose tolerance in type 2 diabetes.
5718 21584282 The SLC2A9 gene encodes the glucose transporter 9, with the abilities of transporting both glucose and uric acid and is involved in the pancreatic glucose-stimulated insulin secretion.
5719 21603234 These results suggest that the extract from A. indicum L. may be beneficial for reducing insulin resistance through its potency in regulating adipocyte differentiation through PPAR? agonist activity, and increasing glucose utilization via GLUT1.
5720 21603268 Evidence from Ucp((-/-)) mice revealed a role of UCP2 in the pancreatic ?-cell, because ?-cells without UCP2 had increased glucose-stimulated insulin secretion.
5721 9267149 The activities and levels of F-VII, F-X, and PAI-1 correlated with triglycerides in serum and also with fasting insulin levels in hyperlipidemic patients with atherosclerotic vascular disease.
5722 10689893 As suggested by the genetic studies in C. elegans, it was recently demonstrated that FKHR, FKHRL1 and AFX, which are mammalian homologues of daf-16 forkhead transcription factor, function downstream of insulin signaling and Akt/PKB under cellular conditions.
5723 21471167 The changes in plasma vaspin levels were positively associated with the amelioration of insulin resistance (IR) shown by the changes in homeostasis model assessment of IR.
5724 21486111 We aimed to investigate the relationship between serum osteoprotegerin (OPG) level and glycemic control, lipids, renal function, microalbuminuria, insulin resistance and markers of atherosclerosis including C-reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate (ESR) in patients with type 2 diabetes mellitus (DM).
5725 16123338 Mice with heart-specific overexpression of peroxisome proliferator-activated receptor (PPAR)alpha showed a metabolic and cardiomyopathic phenotype similar to the diabetic heart, and we determined tissue-specific glucose metabolism and insulin action in vivo during hyperinsulinemic-euglycemic clamps in awake myosin heavy chain (MHC)-PPARalpha mice (12-14 weeks of age).
5726 17351147 Insulin improved Akt phosphorylation in the EX group and increased mTOR/S6 kinase 1 phosphorylation and muscle protein synthesis (EX group: 49 +/- 11 to 89 +/- 23; CTRL group: 58 +/- 8 to 57 +/- 12 nmol x min(-1) x 100 ml leg(-1)) in the EX group only (P < 0.05).
5727 20197055 Thus, deletion of p110alpha in liver results in markedly blunted insulin signaling with decreased generation of PIP(3) and loss of insulin activation of Akt, defects that could not be rescued by overexpression of p110beta.
5728 20197055 Together, these data indicate that the p110alpha isoform of PI3K plays a fundamental role in insulin signaling and control of hepatic glucose and lipid metabolism.
5729 20498376 In wild-type littermate mice, PPARgamma activation (i.e. treatment with rosiglitazone) restored euglycemia and reversed high fat diet-induced insulin resistance and glucose intolerance.
5730 20498376 In contrast, PPARgamma activation did not reduce high fat diet-induced hyperglycemia and failed to reverse insulin resistance and glucose intolerance in PFKFB3(+/-) mice.
5731 20498376 Upon inhibition of excessive fatty acid oxidation in PFKFB3/iPFK2-knockdown adipocytes, PPARgamma activation was able to significantly reverse inflammatory signaling and proinflammatory cytokine expression and restore insulin signaling.
5732 21572040 However, a model that additionally includes insulin effects on blood flow in the adipose tissue and GLUT4 translocation due to cell handling can explain all data, but neither of these additions is sufficient independently.
5733 21613223 Modulation of intracellular Ca²? and insulin secretion with pharmacological agents (tolbutamide and diazoxide) suggested a possible role for changes in these parameters in the regulation of Slc39a6 and Slc39a7 but not Slc39a8, nor metallothionein expression.
5734 21628466 Interestingly, treatment of naļve INS-1 cells or murine organotypic islet cultures with recombinant human BMP-3 potently increased their insulin levels and restored the decrease in SMAD2 phosphorylation and insulin gene expression induced by the HNF1A frameshift mutation.
5735 21635764 In the control arteries treated with endothelial nitric oxide synthase inhibitor L-NAME, insulin induced vasoconstriction that was exacerbated in DH rats.
5736 21738894 The adenovirus-mediated overexpression of PDX-1, BETA2/NeuroD and MafA induced insulin gene expression in NPCCs, but not in adult pig pancreatic cells.
5737 21747826 Glucagon-like peptide 1 (GLP-1), whose activity is reduced in insulin resistance, has been implicated in central nervous system function, including cognition, synaptic plasticity, and neurogenesis.
5738 21128120 Insulin sensitivity tended to improve after 6 months; M-value from 5.7 (±1.8) to 7.8 (±2.6) mg/kg/min, P = 0.083 and per cent improvement in M-value was correlated to per cent reduction in PRL levels (r = -0.85, P = 0.034).
5739 21487412 Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate glucose-dependent insulin secretion.
5740 21512962 Peptides of proinsulin and GAD shown to be recognized by CD4+ T cells of type 1 diabetes patients have been selected from the literature and modified with Ii-Key.
5741 21665040 Pharmacologic modulation of incretin pathophysiology by GLP-1 receptor agonists and DPP-4 inhibitors significantly improved glycemic control, benefited ?-cell function, improved dyslipidemia, and lowered the risk of hypoglycemia compared with insulin and sulfonylureas.
5742 2677442 Infusion of insulin did not affect plasma levels of acetaminophen and gastrin, while it produced a dose-dependent suppression of postprandial PP rise in STZ diabetic dogs.
5743 21572010 Our main aim was to investigate whether and how insulin might negatively regulate Akt/eNOS activities via G protein-coupled receptor kinase 2 (GRK2) in aortas from ob/ob mice.
5744 21572010 Akt (at Thr(308)) phosphorylation and eNOS (at Ser(1177)) phosphorylation, and also the ?-arrestin2 protein level, were markedly decreased in the membrane fraction of insulin-stimulated ob/ob aortas (vs. insulin-stimulated lean ones).
5745 21808585 Adiponectin increases insulin sensitivity and ameliorates obesity.
5746 21808585 Resistin, another protein secreted by the adipose tissue, derived its name due to its involvement in the development of insulin resistance.
5747 21808585 Leptin resistance has been associated with development of obesity and insulin resistance.
5748 11179781 Insulin replacement was also associated with a return of hypothalamic AGRP mRNA (111.7+/-8.3% of controls) and NPY mRNA (125.0+/-8.9% of controls) from the elevated levels that were observed in untreated diabetic rats.
5749 11179781 These data indicate that AGRP is a mediator of diabetic hyperhpagia and suggest that insulin can directly influence hypothalamic AGRP and NPY mRNA expression.
5750 16046291 CORT increased plasma insulin levels 50-fold in Pomc-/- versus 14-fold in wild-type mice (P < 0.01) and increased hypothalamic agouti-related protein (AgRP) expression by more than 200% in Pomc-/- versus 40% in wild type (P < 0.05).
5751 17550779 To define the insulin-responsive neurons that mediate these effects, we generated mice with selective inactivation of the insulin receptor (IR) in either pro-opiomelanocortin (POMC)- or agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus.
5752 17550779 While neither POMC- nor AgRP-restricted IR knockout mice exhibited altered energy homeostasis, insulin failed to normally suppress hepatic glucose production during euglycemic-hyperinsulinemic clamps in AgRP-IR knockout (IR(DeltaAgRP)) mice.
5753 17596403 Cultured islets expressing Ang-1 displayed improved viability and enhanced glucose-stimulated insulin secretion in the presence of cytokines.
5754 20371735 To these ends, the following questions are addressed. 1) How is PGC-1alpha regulated, 2) what adaptations are indeed dependent on PGC-1alpha action, 3) is PGC-1alpha altered in insulin resistance, and 4) are PGC-1alpha-knockout and -transgenic mice suitable models for examining therapeutic potential of this coactivator?
5755 20371735 In contrast, a modest ( approximately 25%) upregulation of PGC-1alpha, within physiological limits, does improve mitochondrial biogenesis, fatty acid oxidation, and insulin sensitivity in healthy and insulin-resistant skeletal muscle.
5756 20424219 Insulin glargine significantly reduced endothelin-1 by 7%.
5757 20460426 Our previous studies suggest that the SNARE protein synaptosomal-associated protein of 23 kDa (SNAP23) is involved in the link between increased lipid levels and insulin resistance in cardiomyocytes.
5758 20460426 The objective was to determine whether SNAP23 may also be involved in the known association between lipid accumulation in skeletal muscle and insulin resistance/type 2 diabetes in humans, as well as to identify a potential regulator of SNAP23.
5759 20484013 Moreover, the reduction of ADFP impaired the ability of palmitate to increase insulin secretion.
5760 20484013 These findings demonstrate that ADFP is important in regulation of lipid metabolism and insulin secretion in beta-cells.
5761 20484139 Insulin-induced phosphatidylinositol 3-kinase (PI3K)/Akt signaling and interleukin-6 (IL-6)-instigated JAK/STAT3-signaling pathways in the liver inhibit the expression of gluconeogenic genes to decrease hepatic glucose output.
5762 20484139 Insulin-induced IR-beta-subunit Y1162/Y1163 phosphorylation and PI3K/Akt signaling and IL-6-induced STAT3 phosphorylation were also enhanced in isolated Ptpn2+/- hepatocytes.
5763 20484139 The increased insulin and IL-6 signaling resulted in enhanced suppression of G6pc and Pck1 mRNA.
5764 20484139 Liver TCPTP antagonises both insulin and STAT3 signaling pathways to regulate gluconeogenic gene expression and hepatic glucose output.
5765 20484460 Single-nucleotide polymorphisms in the SH2B1 loci and chromosomal deletions of the SH2B1 loci associate with obesity and insulin resistance in humans.
5766 20501667 We found that, when the ability of insulin to inactivate FoxO1 is blocked after adenoviral delivery of constitutively active FoxO1, glucose increased serum VLDL triglyceride when given both by ip glucose tolerance testing (3.5-fold increase) and by a hyperglycemic clamp (4.6-fold).
5767 20501667 Under both experimental conditions in which insulin signaling to FoxO1 was impaired, we found increased activation of carbohydrate response element binding protein.
5768 20501667 These data suggest that glucose more potently promotes increased serum VLDL when insulin action is impaired, with either low insulin levels or disrupted downstream signaling to the transcription factor FoxO1.
5769 20504897 We set out to determine whether plasma Gas6 levels are associated with altered glucose tolerance, insulin sensitivity, inflammation, and endothelial dysfunction.
5770 20534724 In summary, CCK is up-regulated by islet cells during obesity and functions as a paracrine or autocrine factor to increase beta-cell survival and expand beta-cell mass to compensate for obesity-induced insulin resistance.
5771 20649587 Furthermore, pioglitazone reduced the expression of suppressor of cytokine signalling (SOCS)-3 - considered to be a key link between inflammation and insulin resistance.
5772 20659093 Insulin independent patients had no further hypoglycemic events, hemoglobin A1c levels decreased and renal function remained stable.
5773 21799686 EA stimulated the expression of IRS1 and AKT2 and atropine treatment blocked the EA-induced expression of those insulin signaling proteins.
5774 21799688 This effect may possibly be involved in enhancing beta-cell regeneration and promoting insulin secretion by targeting PPAR? and PDX-1.
5775 21280205 Insulin increases the extraction of glucose from circulation into adipose tissue by recruiting the glucose transporter GLUT4 to the plasma membrane.
5776 21395400 Forced expression (between days 16 and 25) of MafA, a pancreatic maturation factor, resulted in enhanced expression of insulin genes, glucose transporter 2 and glucokinase, and glucose-responsive insulin secretion.
5777 21812222 Understanding of physiopathology increased this last decade, as many mutations in genes playing critical roles in the development of pancreas, have been described: the most common are chromosome 6q anomalies in the case of TND, and mutations in KCNJ11 and ABCC8 genes encoding the subunit of the insulin cell potassium channel in the case of PND.
5778 16814726 A recent paper (Mao et al., 2006) shows that the APPL1 adaptor protein binds to the intracellular domain of adiponectin receptors and mediates some of adiponectin's actions, identifying a novel mechanism linking adiponectin to insulin sensitization.
5779 21294661 In cultured primary hepatocytes, combined DEX and insulin significantly upregulated the transcription of the genes for FAS (1.34-fold) and malic enzyme (1.72-fold).
5780 21294661 Insulin-activated gene expression for SREBP-1 is suggested to be involved in stress-augmented hepatic lipogenesis.
5781 21593184 Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone considered a promising therapeutic agent for type 2 diabetes because it stimulates beta cell proliferation and insulin secretion in a glucose-dependent manner.
5782 21606930 Subjects with chronic SCI develop abnormal platelet function, resulting in the production of atherogenic and thrombogenic factors for the following reasons: (1) the PGI(2) and insulin receptors on their platelets are impaired; (2) thrombin generation and platelet-derived growth factor release are elevated; (3) insulin-induced nitric oxide production by platelets is markedly impaired; and (4) a circulating antibody (immunoglobulin G (IgG)) blocks the antithrombotic effect of both insulin and PGI(2) receptors.
5783 21632533 Our data therefore suggest that activation of FXR with synthetic agonists is not useful for long term management of the metabolic syndrome, as it reduces the BA pool size and subsequently decreases energy expenditure, translating as weight gain and insulin resistance.
5784 21677040 A recent study has suggested that selenoprotein P (SeP), a novel hepatokine, may play a role in the regulation of glucose metabolism and insulin sensitivity.
5785 21804540 Combined haploinsufficiency of FoxO1 and Notch1 markedly raises insulin sensitivity in diet-induced insulin resistance, as does liver-specific knockout of the Notch transcriptional effector Rbp-J?.
5786 21804540 Conversely, Notch1 gain-of-function promotes insulin resistance in a FoxO1-dependent manner and induces glucose-6-phosphatase expression.
5787 21368653 In diabetic rats, STAT3 activation was strongly reduced, as was postC cardioprotection, suggesting that the inability of insulin to restore postC may be attributed to diabetes-induced STAT3-mediated inhibition of PI3K signaling.
5788 21742977 Deletion of BLT-1 prevented high fat-induced loss of insulin signaling in liver and skeletal muscle.
5789 21521748 Confocal microscopy revealed GPR30 expression in islet insulin, glucagon, and somatostatin cells.
5790 21540283 Pancreatic and duodenal homeobox 1 (PDX1), a key pancreatic transcription factor, regulates insulin along with targets involved in insulin processing and secretion.
5791 21586562 Here, we demonstrate that the expression of Angptl2 in epididymal adipose tissue of C57BL/6J mice shows pulsatility and circadian rhythmicity and that the rhythmicity was disrupted in high-fat-fed and leptin receptor-deficient diabetic db/db mice with insulin resistance.
5792 21586562 In cultured adipocytes, recombinant Angptl2 increased adiponectin expression and stimulated insulin sensitivity partially by reducing the levels of tribbles homolog 3, a specific Akt kinase inhibitory protein.
5793 21586562 Conversely, Angptl2 small interfering RNA reduced adiponectin expression, resulting in insulin resistance.
5794 21829703 Endocrine islets from mice with reduced Sox9 gene dosage exhibited normal glucose stimulated insulin secretion.
5795 21412280 Animals injected with the TNC chitosan 92-10-5 (DDA-MW-N:P) showed GLP-1 plasma levels of about fivefold higher than that in non-treated animals and the insulinotropic effect of recombinant GLP-1 was shown by a threefold increase in plasma insulin concentration when compared with untreated animals.
5796 21454245 Angiotensin II has been implicated in a number of pathophysiologic processes with the potential to indirectly or directly influence the pathogenesis of insulin resistance and type 2 diabetes.
5797 21539943 Glucose-dependent insulinotropic polypeptide (GIP) is an insulinotropic incretin hormone that stimulates insulin secretion during a meal.
5798 21647634 After the application of anti-STEAP4 antibodies at 0.002 mg/mL, adipocytes exhibited reduced insulin-stimulated glucose transport by attenuating the phosphorylation of IRS-1, PI3K (p85), and Akt.
5799 21647634 In conclusion, (i) STEAP4 regulates the function of IRS-1, PI3K, and Akt and decreases insulin-induced GLUT4 translocation and glucose uptake; (ii) ROS-related mitochondrial dysfunction may be related to a reduced IRS-1 correlation with the PI3K signaling pathway, leading to insulin resistance.
5800 21669879 In this study, we investigated the physiological function of sphingomyelin synthase 2 (SMS2) using SMS2 knock-out mice, and we found that SMS2 deficiency prevents high fat diet-induced obesity and insulin resistance.
5801 21778879 Ghrelin attenuates insulin secretion through the AMP-activated protein kinase-uncoupling protein 2 pathway.
5802 21778879 An exciting new report describes that leptin can influence insulin release by osteoclastin, a hormone produced by osteoblasts.
5803 21778879 In addition, leptin also mediates insulin secretion through the sympathetic system and via pro-opiomelanocortin neurons, which could serve as the cross-road for leptin and melanocortin signaling pathways.
5804 21447495 However, in this group, serum resistin was not correlated with age, gender, body mass index (BMI), total cholesterol, FBG, insulin, CK, LDH, and the calculated homeostasis model for insulin resistance (HOMA-IR) (p>0.05).
5805 21475143 Examined were the effects of intravenously infused glucose and/or lipids on proximal ER stress sensor activation (PERK, eIF2-?, ATF4, Xbox protein 1 (XBP1s)), unfolded protein response (UPR) proteins (GRP78, calnexin, calreticulin, protein disulphide isomerase (PDI), stress kinases (JNK, p38 MAPK) and insulin signaling (insulin/receptor substrate (IRS) 1/2 associated phosphoinositol-3-kinase (PI3K)) in rat liver.
5806 21562757 The cytokine osteopontin (OPN) was recently shown to be involved in obesity-induced adipose tissue inflammation and reduced insulin response.
5807 21704843 Insulin and VDAC expression were reduced in the ZDF animals in comparison to the lean control rats, while no significant change was seen in glucagon and Ki67 expression at week 17.
5808 21163347 Several recent studies are reviewed that support the concept that direct exposure of mammalian skeletal muscle to an oxidant stress (including hydrogen peroxide) results in stimulation of the serine kinase p38 mitogen-activated protein kinase (p38 MAPK), and that the engagement of this stress-activated p38 MAPK signaling is mechanistically associated with diminished insulin-dependent stimulation of insulin signaling elements and glucose transport activity.
5809 21304221 After binding to its receptor and activating the ?-subunit, insulin is faced with two divergent pathways: one is phosphatidylinositol 3-kinase (PI 3-K) dependent, while another is dependent upon activation of mitogen-activated protein kinase (MAP-K).
5810 21514684 Our data suggest that EGCG treatment ameliorated FFAs-induced peripheral insulin resistance in vivo, and this might be through decreasing oxidative stress and PKC? membrane translocation, activating the AMPK pathway and improving insulin signaling pathway in vivo.
5811 21602124 APN may decrease tyrosin phosphorylation of IRS-1 via the IKK/NF?B pathway and inhibit insulin signaling pathway in the liver, which contributes to hyerlipidemia, hyperglycemia and development of type 2 diabetes.
5812 21635197 Knockout of sphingomyelin synthase 1, which converts ceramide to sphingomyelin, leads to impairment of insulin secretion.
5813 21198995 At baseline, a high serum adiponectin concentration correlated positively with high levels of insulin sensitivity and insulin secretion.
5814 21198995 Low adiponectin concentrations were associated with future diabetes independently of insulin secretion and sensitivity, as well as IGT, IFG, smoking and abdominal obesity.
5815 21213617 Both apoB and apoA1 were significantly associated with obesity when age, sex, diastolic blood pressure, homocysteine, diabetes, and insulin resistance were controlled for.
5816 21506889 Transgenic overexpression of NGN3 and/or PDX1 proteins not only induced direct target genes, such as NEUROD1 and insulin, and but also triggered parts of the gene expression cascade that is involved in pancreatic endocrine differentiation.
5817 21519329 In a recent study, PGE(2) produced in Kupffer cells attenuated insulin-dependent glucose utilization by interrupting the intracellular signal chain downstream of the insulin receptor in hepatocytes.
5818 21519329 OSM in turn attenuated insulin-dependent Akt activation and, as a downstream target, glucokinase induction in hepatocytes, most likely by inducing suppressor of cytokine signaling 3 (SOCS3).
5819 21519329 Thus, induction of OSM production in Kupffer cells by an autocrine PGE(2)-dependent feed-forward loop may be an additional, thus far unrecognized, mechanism contributing to hepatic insulin resistance and the development of NASH.
5820 21824265 Finally, glucagon has a key role in promoting the catabolic consequences associated with states of deficient insulin action, which supports the therapeutic potential in developing glucagon receptor antagonists or inhibitors of glucagon secretion.
5821 21825133 CRH stimulated both cellular content and release of insulin in rat islet and insulinoma cells.
5822 21586696 In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling.
5823 21586696 Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin.
5824 21744283 After 2 years, remission was achieved in 13 of 20 patients (65%), and hemoglobin A1c decreased from 8.1?±?1.8% to 5.9?±?1.1% and homeostasis model assessment of insulin resistance from 5.7?±?3.2 to 1.9?±?0.8 after 12 months.
5825 21771299 ADPN correlated positively with MMRglu (P < 0.05), which, in multiple regression analysis, was dependent of whole-body insulin sensitivity, HbA1c and waist.
5826 21348862 We report that MK-2206 potently inhibits Thr308Akt and Ser473Akt phosphorylation in 3T3-L1 adipocytes (IC50 0.11 and 0.18 ?M respectively) as well as downstream effects of insulin on GLUT4 (glucose transporter 4) translocation (IC50 0.47 ?M) and glucose transport (IC50 0.14 ?M).
5827 21567076 After 4 weeks, the diabetic rats exhibited bone loss, low levels of osteocalcin, insulin-like growth factor-I (IGF-I) and bone alkaline phosphatase (ALP) activity with normal levels of bone tartrate-resistant acid phosphatase (TRAP) and cathepsin K activity, and urinary excretion of deoxypyridinoline (Dpd).
5828 21598304 In obese mice L-4F increases adiponectin levels, improving insulin sensitivity, and reducing visceral adiposity.
5829 21617842 It was recently demonstrated that uncarboxylated OC improves glucose tolerance and insulin sensitivity in mice by increasing the expression and secretion of insulin in ?-cells and of adiponectin in adipocytes.
5830 21664358 To test this hypothesis, we compared four groups of rats to examine whether an increase in galanin secretion stimulated by swimming may reduce insulin resistance.
5831 21664358 These observations suggest that endogenous galanin reduces insulin resistance by increasing GLUT4 contents and promoting GLUT4 transportation from intracellular membranes to plasma membranes in adipocytes.
5832 21744143 Telmisartan, an angiotensin II receptor blocker (ARB), selectively activates peroxisome proliferatoractivated receptor (PPAR)-gamma, and this effect is considered to markedly improve insulin resistance in obese patients with hypertension.
5833 21663979 We have recently shown that GPR120 acts as a physiological receptor of ?3 fatty acids in macrophages and adipocytes, which mediate potent anti-inflammatory and insulin sensitizing effects.
5834 11369711 In addition, oral IL-10 combined with oral myelin oligodendrocyte glycoprotein (MOG) 35-55 reduced relapses in MOG-induced EAE in the NOD mouse, as well as enhanced the protective effect of oral insulin in the NOD model of diabetes.
5835 21527868 Specifically, we found that the native Cx36 does not alter islet size or insulin content, whereas the Cx43 isoform increases both parameters, and Cx32 has a similar effect only when combined with GH.
5836 21647189 Glucagon-like peptide 1 (GLP-1), a peptide secreted from the intestine in response to nutrient ingestion, is perhaps best known for its effect on glucose-stimulated insulin secretion.
5837 21519965 We subsequently assessed the effect of aldosterone on insulin secretion in vitro in the presence or absence of mineralocorticoid receptor antagonists in isolated C57BL/6J islets and in the MIN6 beta cell line.
5838 21519965 This was not attributable to differences in potassium or angiotensin II, as glucose-stimulated insulin secretion was enhanced in As (-/-) mice even during high sodium intake.
5839 21519965 In islet and MIN6 beta cell studies, aldosterone inhibited glucose- and isobutylmethylxanthine-stimulated insulin secretion, an effect that was not blocked by mineralocorticoid receptor antagonism, but was prevented by the superoxide dismutase mimetic tempol.
5840 21538175 The mechanism(s) behind this glucose intolerance in PSEN1 and APP/PSEN1 mice appeared to involve increased levels of brain retinol-binding protein 4 and basal phosphorylation of S6 ribosomal protein, and decreased insulin-stimulated phosphorylation of Akt/protein kinase B and extracellular signal-regulated kinase 1/2 in the brain.
5841 21614569 This effect was accompanied by a significant increase in insulin content and Pdx1 expression, and a significant decrease of apoptosis and Bax expression in pancreatic islets from db/db mice.
5842 21618241 FFAR1 facilitates glucose-stimulated insulin secretion from pancreatic ?-cells, whereas GPR120 regulates the secretion of glucagon-like peptide-1 in the intestine, as well as insulin sensitivity in macrophages.
5843 21771884 GLP-1 regulates blood glucose through multiple mechanisms, principally inhibition of glucagon and stimulation of insulin secretion.
5844 21771891 Because GLP-1 is known to stimulate insulin secretion and to have effects on energy balance, we mated LGsKO mice with germline GLP-1 receptor (GLP-1R) knockout mice (Glp1r(-/-)) and compared LGsKO to double-knockout (LGs/Glp1r(-/-)) mice to determine the contribution of excess GLP-1R signaling to the LGsKO phenotype.
5845 11375341 Insulin stimulation of phosphatidylinositol 3-kinase activity and phosphorylation of protein kinase B were not decreased by indinavir.
5846 21547502 Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well as CD36 to translocate to the sarcolemma.
5847 21658378 Oral administration of ?-sitosterol (20 mg/kg body weight) once daily for 21 days in STZ-induced diabetic rats resulted in a significant decrease in blood glucose and glycosylated hemoglobin with a significant increase in plasma insulin level, body weight and food intake.
5848 21658378 A significant decrease in the activities of alanine aminotransaminase, aspartate aminotransaminase, alkaline phosphatase and acid phosphatase in ?-sitosterol treated rats when compared to diabetic control rats indicated its protective role against liver damage. ?-Sitosterol increased insulin secretion in response to glucose.
5849 21611789 The diabetogenic role of CDKAL1 variants is suggested to consist in lower insulin secretion probably due to the insufficient inhibition of the CDK5 activity.
5850 21715553 Insulin resistance was measured by hyperinsulinemic euglycemic clamps in mice injected with mimetics of meso-diaminopimelic acid-containing PGN or the minimal bioactive PGN motif, which activate NOD1 and NOD2, respectively.
5851 21715553 Conversely, direct activation of NOD1 protein caused insulin resistance.
5852 21715553 NOD1 ligand elicited minor changes in circulating proinflammatory mediators, yet caused adipose tissue inflammation and insulin resistance of muscle AS160 and liver FOXO1.
5853 21715553 Ex vivo, NOD1 ligand caused proinflammatory cytokine secretion and impaired insulin-stimulated glucose uptake directly in adipocytes.
5854 21715553 NOD1 ligand also caused inflammation and insulin resistance directly in primary hepatocytes from WT, but not NOD1(-/-), mice.
5855 21715553 Acute activation of NOD proteins by mimetics of bacterial PGNs causes whole-body insulin resistance, bolstering the concept that innate immune responses to distinctive bacterial cues directly lead to insulin resistance.
5856 21756351 We conducted a cross-sectional study in 6,720 subjects from the Twins UK Registry to evaluate the association between 18 single nucleotide polymorphisms (SNPs) in five genes (TLR4, IL1A, IL6, TNFA, and CRP) along the innate immunity-related inflammatory pathway and biomarkers of predisposition to T2DM [fasting insulin and glucose, HDL- and LDL- cholesterols, triglycerides (TGs), amyloid-A, sensitive C-reactive protein (sCRP) and vitamin D binding protein (VDBP) and body mass index (BMI)].
5857 21756351 Fasting insulin was associated with SNPs in IL6 and TNFA, serum HDL-C with variants of TNFA and CRP and serum sCRP level with SNPs in CRP.
5858 21810595 By analogy to pancreatic ?-cells where GLP-1 activates protein kinase C (PKC) to stimulate insulin secretion, we postulated that PKC enzymes would be molecular targets of brain GLP-1 signaling that regulate metabolic and vascular function.
5859 21810601 In addition, OPN stimulated cell proliferation in insulin-secreting cells.
5860 21816980 Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycemia by increasing urinary glucose excretion independent of insulin and may cause fewer of these adverse effects.
5861 21680774 Similarly, inhibition of JNK1 kinase by expression of dominant-negative JNK1 also resulted in improved hepatic insulin signaling, indicating that IKK and JNK1 kinases contribute to critical illness-induced insulin resistance in liver.
5862 21876979 Postprandial secretion of peptide YY and Glucagon-like peptide-1 were enhanced, whereas hemoglobin A1c, fasting and postprandial glucose, insulin, and triglyceride levels were significantly reduced.
5863 20511357 This study investigated the associations of plasma leptin levels with insulin resistance (IR) and prediabetes in relatively lean, rural Chinese men and women.
5864 21111773 Aromatase inhibitors, the most effective endocrine agents of breast carcinoma, retinoids, metabolites of vitamin A, and synthetic peroxisome proliferator-activated receptor (PPAR) gamma ligands, used for the treatment of insulin resistance in type II diabetes mellitus, may be the important candidates for possible endocrine treatment of endometrial carcinoma.
5865 21364956 Utilizing an in vitro system, we show that insulin stimulates heparanase secretion by kidney 293 cells, and even higher secretion is observed when insulin is added to cells maintained under high glucose conditions.
5866 21679097 INTRODUCTION: Inhibition of dipeptidyl peptidase IV (DPP-4) augments glucose-dependent insulin release and is a new approach to the treatment of type 2 diabetes (T2DM).
5867 21841312 Mice with pancreatic ? cell-specific KO of Cdkal1 (referred to herein as ? cell KO mice) showed pancreatic islet hypertrophy, a decrease in insulin secretion, and impaired blood glucose control.
5868 21435176 Whereas the density of brain insulin receptor decreases during age, IGF-1 receptor increases, suggesting that specific insulin-mediated signals is involved in aging and possibly in cognitive decline.
5869 21886784 Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells.
5870 21887289 The diabetogenic alleles of DGKB and PROX1 were nominally associated with reduced insulin secretion.
5871 21887289 Nominally significant effects on insulin sensitivity could be found for MADD and PROX1.
5872 20530740 As shown in the in vitro analysis, the low-grade proinflammatory environment and the insulin resistance associated with obesity may contribute to downregulate LPIN1 in adipose tissue, leading to a worse metabolic profile.
5873 21557442 In addition, low-dose prolactin decreased hepatic glucose output in hyperinsulinaemic states, indicating an improvement in hepatic insulin resistance.
5874 21564460 The role of cannabinoid receptors in human islets of Langerhans has not been investigated in any detail, so the current study examined CB1 and CB2 receptor expression by human islets and the effects of pharmacological cannabinoid receptor agonists and antagonists on insulin secretion.
5875 21564460 RT-PCR showed that both CB1 and CB2 receptors are expressed by human islets and immunohistochemistry indicated that receptor expression co-localized with insulin-expressing ?-cells.
5876 21564460 Perifusion experiments using isolated human islets showed that insulin secretion was reversibly stimulated by both CB1 and CB2 receptor agonists, with CB1 receptor activation associated with increased basal secretion whereas CB2 receptors were coupled to initiation and potentiation of insulin secretion.
5877 21564460 Antagonists at CB1 (N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) and CB2 (N-(1,3-Benzodioxol-5-ylmethyl)-1,2-dihydro-7-methoxy-2-oxo-8-(pentyloxy)-3-quinoline carboxamide) receptors failed to inhibit the stimulatory effects of the respective agonists and, unexpectedly, reversibly stimulated insulin secretion.
5878 21652728 Leptin-induced NS proliferation was significantly greater than that induced by insulin, although both effects were blocked by Notch, extracellular signal-regulated kinase, or signal transducer and activator of transcription 3 inhibition.
5879 21673097 Both estradiol and G-1 induced insulin secretion under low- and high-glucose conditions, which was inhibited by pretreatment with GPER antagonist G15 as well as depletion of GPER by small interfering RNA.
5880 21673097 Insulin secretion in response to estradiol and G-1 was dependent on epidermal growth factor receptor and ERK activation and further modulated by phosphatidylinositol 3-kinase activity.
5881 21673097 In islets isolated from wild-type mice, the GPER antagonist G15 inhibited insulin secretion induced by estradiol and G-1, both of which failed to induce insulin secretion in islets obtained from GPER knockout mice.
5882 21673097 Our results indicate that GPER activation of the epidermal growth factor receptor and ERK in response to estradiol treatment plays a critical role in the secretion of insulin from ?-cells.
5883 21750415 An immunofluorescence technique was used to examine the expression of resistin and its co-localization with insulin and glucagon in pancreatic islet cells.
5884 21750415 Resistin co-localized with insulin but not glucagon in pancreatic islet cells of both normal and diabetic patients.
5885 21765243 Moreover, hPL-A induced PDX-1 intracellular expression, improving beta cell activity and ameliorating insulin secretion in response to high glucose stimulation.
5886 21586699 To investigate the effect of specific Kv1.3 inhibition on insulin sensitivity in vivo, PAP-1 was administered to hyperglycemic mice either acutely or for 5 days prior to an insulin tolerance test.
5887 21586699 Insulin sensitivity was increased only when plasma concentrations of PAP-1 were sufficient to inhibit other Kv1 channels.
5888 21615774 Upregulated expression of TRX and insulin and downregulated expression of TXNIP were observed in probucol-treated diabetic rats.
5889 21675944 Thiazolidinediones (TZDs) are potent exogenous agonists of PPAR-gamma, which augment the effects of insulin to its cellular targets and mainly at the level of adipose tissue.
5890 21904679 We tested the hypothesis that TAG accumulation in the liver induced by short-term high-fat diet (HFD) in rats leads to the dysregulation of endogenous TAG degradation by lysosomal lipase (LIPA) via lysosomal pathway and is causally linked with the onset of hepatic insulin resistance.
5891 21255422 GLP-1 increased serum insulin at 270 minutes (GLP-1: 23.4 ± 6.7 vs. placebo: 16.4 ± 5.5 mU/l; P < 0.05), but had no effect on the change in plasma glucagon.
5892 21255422 Given the modest magnitude of the reduction in glycaemia the effects of GLP-1 at higher doses and/or when administered in combination with insulin, warrant evaluation in this group.
5893 21544727 PPAR?, which is abundant in adipose tissue, stimulates adipocyte differentiation and adipogenesis, and results in an increase in insulin sensitivity.
5894 21554520 To study the effect of dipeptidyl peptidase-4 (DPP-4) inhibition with saxagliptin on ?-cell function as reflected by the stimulated insulin secretion rate after an enteral glucose load in patients with type 2 diabetes.
5895 21653675 CD34(+)KDR(+) and CD34(+)CD133(+)KDR(+) cells were inversely correlated with the area-under-the-glucose-curve (p<0.005, for both) and positively to insulin secretion-sensitivity index (p<0.05, for both).
5896 21784843 We have used an insulin-secreting cell line with inducible expression of dominant negative (DN) HNF1?, a transcription factor vital for correct ?-cell development and function, to show that HNF1? is required for Xbp1 transcription and maintenance of the normal ER stress response.
5897 21784843 Rat insulin 2 promoter-DN HNF1? mouse islets express lower levels of BiP mRNA, synthesize less insulin, and are sensitized to ER stress relative to matched control mouse islets, suggesting that this mechanism is also operating in vivo.
5898 21811961 In morbid obesity: (1) Subcutaneous adipose tissue releases interleukin-6 which could then mediate insulin resistance in skeletal muscle. (2) Although there is increased secretion of leptin by the subcutaneous adipose tissue, leptin levels are not correlated to the sensitivity of glucose metabolism to insulin in muscle.
5899 21816162 In this study, we examined whether CETP affected the insulin-mediated responses in adipocytes.
5900 21816162 Human CETP expression increased cellular cholesterol levels and enhanced insulin-stimulated Akt phosphorylation and glucose uptake in adipocytes.
5901 21821372 This study aimed to evaluate the association of serum inflammatory markers (C-reactive protein (CRP) and uric acid (UA)), magnesium and other CVD risk factors with insulin resistance (IR) among Chinese postmenopausal women with prediabetes.
5902 21839662 Although insulin-like growth factor-I (IGF-I) and dehydroepiandrosterone-sulfate (DHEA-S) are involved in age-related diseases such as cardiovascular disease and diabetes mellitus, the association of these hormones with serum adiponectin level is still unclear.
5903 21907143 The protein kinase B(?) (Akt2) pathway is known to mediate insulin-stimulated glucose transport through increasing glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane (PM).
5904 21907143 Interestingly, CDP138 is dynamically associated with the PM and GLUT4-containing vesicles in response to insulin stimulation.
5905 19807652 Insulin sensitizers such as biguanides or AMP-activated protein kinase activator, but not glitazones, afforded cytoprotection through preventing (Deltapsi(m) collapse and activation of caspase-9 that was independent of cellular GSH.
5906 19903374 It has been recently reported that blockade of type 1 cannabinoid (CB1) receptors by specific antagonists or genetic manipulation alleviates dyslipidaemia, hyperglycaemia and insulin resistance in animal models of obesity and type 2 diabetes.
5907 21518259 There was a minor but significant postprandial decrease in ICAM, CRP and vWF on both insulin regimens and a decrease in fibrinogen on NPH insulin.
5908 21677415 Retinol-binding protein 4 (RBP4) has been shown to be associated with insulin resistance and fatty acid metabolism.
5909 19019231 Exercise training significantly (p < .05) increased plantaris muscle cytochrome oxidase, significantly improved glycosylated hemoglobin (sed: 7.33 +/- 0.56%; train: 6.1 +/- 0.18%), ad improved insulin sensitivity.
5910 21705657 RNAi knockdown experiments established that HIP14 is an antiapoptotic protein required for ?-cell survival and glucose-stimulated insulin secretion.
5911 21829168 Here, we show that an early response transcription factor Egr-1 could tilt the signalling balance by blocking PI3K/Akt signalling through PTEN and augmenting Erk/MAPK signalling through GGPPS, resulting in insulin resistance in adipocytes.
5912 21829168 Therefore, we have revealed, for the first time, the mechanism by which Egr-1 induces insulin resistance under hyperinsulinism stress, which provides an ideal pharmacological target since inhibiting Egr-1 can simultaneously block MAPK and augment PI3K/Akt activation during insulin stimulation.
5913 21876517 Our findings point to that hyperprolactinemia due to 1st and 2nd generation antipsychotics may decrease insulin sensitivity, whereas other mechanisms probably underlie insulin resistance induced by PRL-sparing antipsychotics such as clozapine and olanzapine.
5914 21746792 This insulin sensitivity profile was in agreement with glucose transporter 4 expression and translocation in skeletal muscle, and insulin signaling, phosphoenolpyruvate carboxykinase/glucose-6-phosphatase expression and glycogen storage in the liver.
5915 21795304 The aim of this study was to identify mechanisms which switch processing of proglucagon to generate GLP-1 in the pancreas, given that GLP-1 can increase insulin secretion and ?-cell mass.
5916 21814547 TCF7L2 variants have been associated with type 2 diabetes, body mass index (BMI), and deficits in proinsulin processing and insulin secretion.
5917 18846471 Co-incubation with insulin had no additional effect, but the cellular uptake was decreased by wortmannin and SB 203580, specific inhibitors of phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (p38 MAPK), respectively.
5918 20957006 The level of fasting insulin was higher in OLETF rats than that of LETO rats only at the age of 28 weeks [(68.17±13.35)×10(-3) vs (19.61±0.20)×10(-3) U/L, P<0.01]. (2) Glycerol released from epididymal adipose tissues of OLETF rats was increased by 34.7% compared with LETO rats at the age of 18 weeks [(213.0±12.5) vs (158.2±11.7) nmol/(g×h), P<0.05], whereas at the age of 28 weeks, it was reduced by 33.5% [(210.2±37.8) vs (315.9±25.0) nmol/(g×h), P<0.05]. (3) In OLETF rats, HSL protein level was not altered at the age of 18 weeks, but down-regulated at the age of 28 weeks.
5919 21395477 Apelin and its receptor have emerged as promising targets for the treatment of insulin resistance.
5920 21395477 Indeed, peripheral administration of apelin stimulates glucose utilization and insulin sensitivity via a nitric oxide (NO) pathway.
5921 16968811 In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance.
5922 18098039 Peroxisome proliferator-activated receptors (PPAR) are involved in the pathogenesis of insulin resistance, diabetes, and related complications.
5923 21183729 Protein content for membrane glucose transporters (GLUT-1 and GLUT-4) was depressed in diabetic heart; the observed alteration in GLUT-4 was partially prevented by both sarpogrelate and insulin, whereas that in GLUT-1 was attenuated by sarpogrelate only.
5924 21539480 Because physical inactivity may share elevated pro-inflammatory (tumor necrosis factor-alpha and inducible nitric oxide synthase) and insufficient stress response (insulin-like growth factor-1 [IGF-1], heat-shock protein 25 [HSP25], NAD-dependent deacetylase sirtuin-3 [SIRT-3], and peroxisome proliferator-activated receptor-gamma coactivator 1[PGC-1?]) signaling with aging and chronic disease, it is critical to distinguish true aging from chronic inactivity or underlying disease.
5925 21820611 There was no difference between groups in adipokines; however, in women with a healthy pregnancy, RBP4 was associated with insulin resistance (r = 0.47, p <0.05).
5926 21820611 RBP4 was associated with insulin resistance only in women with a previous healthy pregnancy (r = 0.51, p <0.05).
5927 21819598 We propose that higher dynamics in glycated insulin could prevent the formation of the rigid cross-? core structure found in amyloid fibrils, thereby contributing to the reduction in the ability to form fibrils and to the population of different aggregation pathways like the formation of native-like aggregates.
5928 21865331 In NASH, the LOX-1 polymorphism is associated with liver disease severity and may predispose to CVD through modulation of postprandial small TRLPs and adipokine balance and to diabetes by affecting both insulin secretion and insulin sensitivity.
5929 21932576 Leptin and adiponectin levels were significantly correlated with anthropometric parameters, HOMA-IR and insulin in all subjects and with fasting glucose in girls only.
5930 21935427 We demonstrated that oligomannuronate, especially its chromium (III) complexes, enhanced insulin-stimulated glucose uptake and increased the mRNA expression of glucose transporter 4 (GLUT4) and insulin receptor (IR) after their internalization into C2C12 skeletal muscle cells.
5931 21935427 Additionally, oligosaccharides treatment also significantly enhanced the phosphorylation of proteins involved in both AMP activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways in C2C12 cells, indicating that the oligosaccharides activated both the insulin signal pathway and AMPK pathways as their mode of action.
5932 21569294 The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is an important candidate for causing insulin resistance.
5933 21757715 GLUT4 dramatically changes its distribution upon insulin stimulation, and insulin-resistant diabetes is often linked with compromised translocation of GLUT4 under insulin stimulation.
5934 21810948 More importantly, acute insulin stimulation after chronic insulin treatment resulted in blunted phosphorylation of Akt, p70S6K, and glycogen synthase kinase-3?.
5935 21810948 Interestingly, when the cells were treated with phosphatidylinositol 3-kinase pathway inhibitor, but not MAPK pathway inhibitor, chronic insulin treatment did not block acute insulin treatment-induced Akt phosphorylation.
5936 21846802 After weight loss, skeletal muscle NIK protein was significantly reduced in association with increased plasma adiponectin and enhanced AMP kinase phosphorylation and insulin sensitivity in obese subjects.
5937 21846802 The decrease in insulin-stimulated glucose uptake was associated with a significant decrease in PI3 kinase activity and protein kinase B/Akt phosphorylation.
5938 21846802 Overexpression of NIK kinase-dead dominant negative did not affect insulin-stimulated glucose uptake.
5939 21846802 Adiponectin treatment inhibited NIK-induced NF-?B activation and restored insulin sensitivity by restoring PI3 kinase activation and subsequent Akt phosphorylation.
5940 21846802 These results indicate that NIK induces insulin resistance and further indicate that adiponectin exerts its insulin-sensitizing effect by suppressing NIK-induced skeletal muscle inflammation.
5941 21912382 The improved insulin release and glucose tolerance after GBP were shown by others to be blocked by the administration of a GLP-1 antagonist, demonstrating that the favorable metabolic changes after GBP are, in part, GLP-1 dependent.
5942 19521344 Consistent with impaired insulin signaling, we found that insulin-stimulated 3T3-L1 adipocytes exhibited decreased IRS-1(Tyr) phosphorylation, increased IRS-1(Ser) phosphorylation, and impaired Akt phosphorylation when treated with 12/15-LO product.
5943 21834910 Animal studies have shown that the peroxime proliferator-activated receptor delta (PPARD) gene regulates glucose metabolism and insulin sensitivity.
5944 15277534 The acute effect of insulin on GLUT4 translocation and glucose uptake was diminished in 3T3-L1 adipocytes exposed to a physiological level of insulin (5 nm) for 12 h.
5945 15685173 Insulin resistance was improved by systemic neutralization of IL-6 or salicylate inhibition of IKK-beta.
5946 15919791 Concomitant with a time-dependent loss of insulin sensitivity, ET-1 caused a parallel reduction in plasma membrane PIP(2).
5947 15919791 Despite decreased insulin-stimulated PI 3-kinase activity and PIP(3) generation, ET-1 did not diminish downstream signaling to Akt-2.
5948 15919791 Furthermore, addition of exogenous PIP(2), but not PIP(3), restored insulin-regulated GLUT4 translocation and glucose transport impaired by ET-1.
5949 16240321 Endothelin-1 (ET-1) disrupts insulin-regulated glucose transporter GLUT4 trafficking.
5950 16240321 Since the negative consequence of chronic ET-1 exposure appears to be independent of signal disturbance along the insulin receptor substrate-1/phosphatidylinositol (PI) 3-kinase (PI3K)/Akt-2 pathway of insulin action, we tested if ET-1 altered GLUT4 regulation engaged by osmotic shock, a PI3K-independent stimulus that mimics insulin action.
5951 16240321 Both insulin and hyperosmotic stress signaling to Cbl were impaired by ET-1.
5952 16240321 In addition to showing for the first time the important role of PIP2-regulated cytoskeletal events in GLUT4 regulation by stimuli other than insulin, these studies reveal a novel function of PIP2/actin structure in signal transduction.
5953 17174134 Serum retinol binding protein 4 (RBP4) was recently described as a new adipokine that reduced peripheral and hepatic insulin sensitivity and increased hepatic gluconeogenesis.
5954 17174134 Hence, sequence variants that alter RBP4 expression or function could increase T2DM susceptibility and reduce insulin sensitivity.
5955 17914034 The apoE(-/-) mice exhibited lower body weight and insulin levels than apoE(+/+) mice when fed the diabetogenic diet.
5956 18220662 Following current considerations of insulin signals regulating GLUT4, this review will focus on in vitro and in vivo evidence that supports an essential role for phosphoinositides and actin filaments in the control of glucose transport.
5957 18450419 These include genes of the major histocompatibility complex (MHC), polymorphisms 5' of the insulin gene, and PTPN22, as well as more recently defined loci from genome-wide association studies.
5958 18653708 Insulin replacement prevented the decrease in IRS-1/Akt phosphorylation, the increase in proteolysis, and attenuated the increase in ubiquitin mRNA.
5959 18716158 Adiponectin (adipoQ) gene variants have been associated with type 2 diabetes mellitus and insulin resistance.
5960 18716158 Our aim was to examine whether the presence of several polymorphisms at the adipoQ gene locus (-11391 G > A, -11377 C > G, 45 T > G, and 276 G > T) influences the insulin sensitivity to dietary fat.
5961 18769905 Overexpression of PC in INS-1 cells led to an elevation of insulin secretion and cell proliferation, whereas inhibition of PDH activity by overexpressing Pdk4 in INS-1 cells did not reduce insulin secretion.
5962 19423845 We previously showed that CRP inhibits eNOS activation by insulin by blunting Ser1179 phosphorylation.
5963 19423845 We first show in mice that CRP inhibits insulin-induced eNOS phosphorylation, indicating that these processes are operative in vivo.
5964 19423845 In endothelial cells we find that CRP attenuates insulin-induced Akt phosphorylation, and CRP antagonism of eNOS is negated by expression of constitutively active Akt; the inhibitory effect of CRP on Akt is also observed in vivo.
5965 19423845 Furthermore, we find that endothelium express SHIP-1 (Src homology 2 domain-containing inositol 5'-phosphatase 1), that CRP induces SHIP-1 stimulatory phosphorylation in endothelium in culture and in vivo, and that SHIP-1 knockdown by small interfering RNA prevents CRP antagonism of insulin-induced eNOS activation.
5966 19423845 Thus, CRP inhibits eNOS stimulation by insulin via FcgammaRIIB and its ITIM, SHIP-1 activation, and resulting blunted activation of Akt.
5967 20956025 In contrast, incubation of iDCs with proinsulin partially suppressed CD86 co-stimulatory factor mediated DC activation, while incubation of iDCs with CTB-INS fusion protein completely suppressed iDC biosynthesis of both CD86 and CD83 costimulatory factors.
5968 20956025 Taken together, the experimental data suggests Toll like receptor 2 (TLR-2) plays a dominant role in CTB mediated INS inhibition of DC induced type 1 diabetes onset in human Type 1 diabetes autoimmunity.
5969 21352888 In the pituitary, insulin treatment prevented diabetes-induced apoptosis (P<0.01), as well as the decline in prolactin and GH mRNA levels (P<0.05).
5970 8995188 The two functional members are contained within an area of the MHC which has been associated with increased susceptibility to autoimmune diseases such as insulin-dependent diabetes mellitus and also rapid progression to AIDS following HIV-1 infection.
5971 21585522 On the basis of a specific radioimmunoassay, insulin secretion was found to be more strongly reduced in the clones expressing hMT2 than in INS-1 controls, when incubated with 1 or 100 nm melatonin.
5972 16126724 In liver, insulin suppresses gluconeogenesis by inhibiting the transcriptions of phosphoenolpyruvate carboxylase (PEPCK) and glucose-6-phosphatase (G6Pase) genes.
5973 16126724 The mitogen-activated dual specificity protein kinase phosphatase 3 (MKP-3) was identified as a candidate gene that antagonized insulin suppression on PEPCK gene transcription from this screen.
5974 16126724 Therefore, dysregulation of MKP-3 expression and/or function in liver may contribute to the pathogenesis of insulin resistance and type II diabetes.
5975 21635674 Glucagon-like peptide-1 (GLP-1) is an incretin hormone that induces glucose-dependent insulin secretion and may have neurotrophic properties.
5976 21775499 Gene expression of NDUFA5, NDUFA10, COX11, and ATP6V1H correlated positively with glucose-stimulated insulin secretion (P<0.03).
5977 21802961 Plasma vaspin levels were positively associated with the fasting insulin and the homeostasis model assessment of IR (HOMA-IR).
5978 21802961 And rosiglitazone therapy decreased plasma vaspin levels through glucose and insulin sensitivity regulation.
5979 21852673 Apical GLUT2 location was absent in lean subjects but was observed in 76% of obese subjects and correlated with insulin resistance and glycemia.
5980 21873554 On an HFD, adipocyte-specific ARNT knockout mice and adipocyte-specific HIF1? knockout mice exhibit similar metabolic phenotypes, including reduced fat formation, protection from HFD-induced obesity, and insulin resistance compared with similarly fed wild-type controls.
5981 21873554 The improvement of insulin resistance is associated with decreased expression of Socs3 and induction of adiponectin.
5982 21873554 Inhibition of HIF1 in adipose tissue ameliorates obesity and insulin resistance.
5983 21885870 We studied their role in the control of the free ER Ca(2+) concentration ([Ca(2+)](ER)) and the role of SERCA3 in the control of insulin secretion and ER stress. ?-Cell [Ca(2+)](ER) of SERCA3(+/+) and SERCA3(-/-) mice was monitored with an adenovirus encoding the low Ca(2+)-affinity sensor D4 addressed to the ER (D4ER) under the control of the insulin promoter.
5984 21885870 SERCA3 deficiency neither impairs Ca(2+) uptake by the ER upon cell metabolism acceleration and insulin release nor induces ER stress.
5985 21937027 Although palmitate did not impair insulin signaling as shown by the immunoblotting analysis of AKT phosphorylation, it did inactivate AMP-activated protein kinase (AMPK).
5986 21940780 Id1 expression plays an essential role in the etiology of glucose intolerance, insulin secretory dysfunction, and ?-cell dedifferentiation under conditions of increased lipid supply.
5987 21949805 Bone morphogenetic protein 4 (Bmp4)-Bmp receptor 1A signaling in ? cells has recently been reported to be required for insulin production and secretion.
5988 21962514 Saturated FA, but not unsaturated FA, activate Jun N-terminal kinase (JNK), which has been linked to obesity and insulin resistance in mice and humans.
5989 21962515 Protein tyrosine phosphatase 1B (PTP1B) plays important roles in downregulation of insulin and leptin signaling and is an established therapeutic target for diabetes and obesity.
5990 21966330 Activation of PPAR-gamma receptors leads to a decrease in insulin resistance and modification of adipocyte metabolism.
5991 21966330 Dual or pan PPAR ligands stimulate two or more isoforms of PPAR and thereby reduce insulin resistance and prevent short- and long-term complications of diabetes including micro-and macroangiopathy and atherosclerosis, which are caused by deposition of cholesterol.
5992 21966368 BMI, plasma insulin levels and HOMA-IR correlated negatively with LPL expression in both VAT and SAT as well as with FABP4 expression in VAT.
5993 20813966 This Commentary discusses how suppressor of glucose by autophagy (SOGA) contributes to adiponectin-mediated insulin-dependent inhibition of autophagy during the activation of adenosine monophosphate kinase (AMPK).
5994 20880397 However, these PI3K inhibitors all abolished insulin-induced Na(+) absorption and inactivated PI3K, SGK1 and PKB fully.
5995 20880397 GSK650394A, on the other hand, selectively inhibits SGK1 and the finding that GSK650394A suppressed insulin-induced Na(+) absorption suggests that this response is dependent upon signalling via PI3K/SGK1.
5996 21703998 Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and low-density lipoprotein receptor and suppression of bile salt export pump.
5997 21864757 Moreover, insulin seems to augment cardiomyocyte contraction, while it affects favorably myocardial relaxation, increases ribosomal biogenesis and protein synthesis, stimulates vascular endothelial growth factor (VEGF) and thereby angiogenesis, suppresses apoptosis, promotes cell survival and finally ameliorates both myocardial microcirculation and coronary artery resistance, leading to increased blood perfusion of myocardium.
5998 21838054 In our CMG-based study of their impact on glycemic variations, it was demonstrated that BGs and TZDs improve hyperglycemia during nighttime and before breakfast more effectively than they do postprandial glycemic excursions; that, of the insulin secretagogues, glinides reduce daily glycemic variations as do alpha-glucosidase inhibitors, while SUs do not affect them very much; and that DPP-4 inhibitors lower not only mean glucose levels which are deemed equivalent to HbAlc values but also narrow the range of glycemic variations.
5999 19794064 However, at day 16 mothers carrying H19(Delta13)-null pups had a significantly higher area under the glucose tolerance test curves than controls (1,845 +/- 378 vs. 1,386 +/- 107 mmol * min * l(-1) [P = 0.01]) in association with increasing pregnancy-related insulin resistance.
6000 21822931 During oral glucose tolerance and hyperglycaemic arginine stimulation tests, the plasma AUC for GLP-1 (730?±?69 vs 1,334?±?288 pmol/l?×?min, p?=?0.0002) and basal and stimulated levels of serum insulin and plasma glucagon were ?50% decreased (p?
6001 21822931 Re-sequencing of GCG revealed a low frequency intronic variant, rs4664447, and follow-up physiological studies suggest that this variant in homozygous form may cause decreased fasting and stimulated levels of insulin, glucagon and GLP-1.
6002 21847584 Pharmacological blockade of nNOS was unable to modify beta cell response to glucose in fa/fa rats and in islets from obese individuals, suggesting an abnormal control of insulin secretion by the enzyme.
6003 21850561 We used HPLC-electrospray ionisation (ESI)-MS/MS to quantify IRS-1 phosphorylation basally and after insulin infusion in vastus lateralis muscle from lean healthy, obese non-diabetic and type 2 diabetic volunteers.
6004 21850561 Insulin increased IRS-1 phosphorylation at Ser527 (1.4?±?0.17, p???0.01, fold change, 60 min after insulin infusion vs basal) and Ser531 (1.3?±?0.16, p???0.01, fold change, 60 min after insulin infusion vs basal) in the lean controls and suppressed phosphorylation at Ser348 (0.56?±?0.11, p???0.01, fold change, 240 min after insulin infusion vs basal), Thr446 (0.64?±?0.16, p???0.05, fold change, 60 min after insulin infusion vs basal), Ser1100 (0.77?±?0.22, p???0.05, fold change, 240 min after insulin infusion vs basal) and Ser1142 (1.3?±?0.2, p???0.05, fold change, 60 min after insulin infusion vs basal).
6005 21850561 However, some IRS-1 phosphorylation sites do not respond to insulin, whereas other Ser/Thr phosphorylation sites are either increased or decreased in insulin resistance.
6006 21853325 The screen suggested with high confidence the involvement of several novel genes in cytokine-induced beta cell death, including Camkk2, Epn3, Foxp3 and Tm7sf3, which encodes an orphan seven transmembrane receptor. siRNAs to Tm7sf3 promoted cytokine-induced death of MIN6 cells and human pancreatic islets, and abrogated insulin secretion in these cells.
6007 21861178 Non-cytotoxic MGO concentrations inhibited insulin-induced IRS tyrosine phosphorylation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) pathway activation independently from reactive oxygen species (ROS) production.
6008 21596547 SNAP23 is involved in the insulin dependent translocation of GLUT4 to the plasma membrane, and has an important role in the development of insulin resistance.
6009 21622157 Our results suggest that genistein might be a useful dietary supplement to control insulin-independent diabetes mellitus by inducing the SHARP-2 expression via a bypass of the insulin-dependent signaling pathway.
6010 21839831 We observed an elevation of all biomarkers for oxidative stress, generation of ROS and activation of NFkB and down regulation in expression of insulin, GLUT2 and glucokinase in hyperglycemic mice.
6011 21940282 Whereas somatostatin and insulin both suppressed the increase in glucagon secretion stimulated by high levels of glucose, leptin had no such effect.
6012 21982711 These data show that insulin signaling through Akt2 promotes anabolic lipid metabolism independent of Foxa2 or FoxO1 and through pathways additional to the mTORC1-dependent activation of SREBP1c.
6013 21803028 In corresponding Ang-IV treated animals, insulin induced IRAP and PI3K interaction, activation of pAkt and GLUT4 translocation, but no corresponding activation of IR, IRS-1 and IRS-1-PI3K coupling were observed.
6014 21803028 Ang-IV acts via IRAP, which couples PI3K and activates the later part of the insulin pathway.
6015 21977024 In conditions of over-nutrition, increased insulin (INS) and angiotensin II (Ang II) activate mammalian target for rapamycin (mTOR)/p70 S6 kinase (S6K1) signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue.
6016 21977024 Conversely, alcohol-mediated inhibition of mTOR/S6K1, down-regulation of INS receptor and growth-inhibitory mir-200 family, and upregulation of mir-212 that promotes fetal gene program may exacerbate CRS-related cardiomyopathy.
6017 21985371 Activation of TLR-5 in islets lead to a marked reduction of both stimulated and basal secretion of insulin, as well as an increase in production of nitric oxide, proinflammatory cytokines, anti-inflammatory heat-shock protein and major histocompatibility complex (MHC) class I transporter.
6018 21985371 We suggest that this regulation by TLR-5 might be beneficial during serious infection such as sepsis by limiting the activity of beta cells during peaks of insulin demand to counteract beta cell damage.
6019 21770819 Vaspin is a novel adipocytokine that may link obesity, insulin resistance (IR), and type 2 diabetes mellitus.
6020 21851286 Exogenous GIP enhanced (p < 0.05) glucose-lowering in all groups of rats accompanied by insulin releasing (p < 0.001) effects in insulinoma-bearing and control rats.
6021 21892557 Two studies found a positive association between physical exercises and adequacy of glycemic control on long-term, determining by glycated hemoglobin (HbAlc) and increase the insulin sensitivity, whereas three articles didn't found relations between exercises and glucose, insulin sensitivity and formation of ketone bodies.
6022 15111493 The direct regulation of perilipin and S3-12 by PPAR-gamma therefore is likely to be an important mediator of the in vivo effects of prolonged treatment with PPAR-gamma activators: insulin sensitization, fatty acid trapping in adipose tissue, reduced basal adipose lipolysis, and weight gain.
6023 15182363 Depletion of cholesterol from the cells using beta-cyclodextrin blocked insulin stimulation of glucose uptake, insulin inhibition of perilipin phosphorylation in response to isoproterenol, and insulin stimulation of protein kinase B and Map-kinases extracellular signal-related kinase (ERK)1/2 phosphorylation.
6024 15197189 Despite increasing insulin resistance with age, plin(-/-) mice at different ages maintained a normal glucose response during an intraperitoneal glucose tolerance curve, being compensated by the increased beta-oxidation and reduced hepatic glucose production.
6025 17445544 In conclusion, increased perilipin expression in subcutaneous fat after rosiglitazone treatment is likely to be a mediator of reduced lipolysis, resulting in lipid storage in subcutaneous fat, fat redistribution, and insulin sensitization.
6026 17684441 We showed that insulin inhibited beta-agonist-induced lipolysis at least in part by inhibiting phosphorylation of perilipin and hormone-sensitive lipase (HSL) in 3T3-L1 adipocytes.
6027 18341822 Insulin induced significantly higher CD83 and CD86 expressions on MoDCs in a dose-dependent manner.
6028 18460341 Via reduced release of fatty acids into the circulation, the anti-lipolytic effect could be a mechanism through which FGF21 promotes insulin sensitivity in man.
6029 18972582 The purpose of the present study was to examine the effects of AS-IV on the lipolysis and insulin resistance induced by tumor necrosis factor-alpha (TNFalpha) in cultured 3T3-L1 adipocytes.
6030 21571864 Glucokinase (GK) plays a critical role in controlling blood glucose; GK activators have been shown to stimulate insulin secretion acutely both in vitro and in vivo.
6031 21675944 Dysfunction of peroxisome proliferator activated receptor-gamma (PPAR-gamma) has been implicated in the development of insulin resistance, while a reduce expression of many PPAR-gamma regulated genes has been observed in an obese diabetic state.
6032 21779873 We found that increasing dosage of the C risk allele at SLC30A8 rs13266634 was significantly associated with higher proinsulin levels at baseline (p?=?0.002) after adjustment for baseline insulin.
6033 21779873 At the 1 year analysis, proinsulin levels decreased significantly in all groups receiving active intervention and were no longer associated with SLC30A8 genotype (p?=?0.86) after adjustment for insulin at baseline and 1 year.
6034 21821034 In all three species protein expression of zinc transporter ZnT8 was detected in most of the insulin producing beta cells whereas Zip14 expression was widely expressed in alpha and beta cells.
6035 21945929 In comparison to both the SHG and control groups, IHG conditions induced a more significant impairment of insulin release and calcium influx in response to 1nM GLP-1 treatment.
6036 22001674 These findings suggest that improvements in glucose tolerance and insulin resistance following RYGB surgery are associated with upregulation of IRS-1.
6037 21668495 Omentin-1 and chemerin have been identified as interesting novel adipokines that may modulate insulin action.
6038 21957263 The restorative effect of insulin was prevented by brefeldin A, suggesting that insulin induced TRPV1 receptor trafficking to the terminal membrane.
6039 22019747 Adipose tissue is now regarded as a source of proinflammatory mediators which may contribute to vascular injury, insulin resistance (IR), and atherogenesis, however, some of them have a protective role against vascular inflammation and/or IR; namely adiponectin and nitric oxide (NO).
6040 19586041 Further, the GLP-1 immobilized PEG hydrogels enhance the survival and insulin secretion of encapsulated islets.
6041 21705951 After calcium injection into the artery supplying the insulinoma, a significant 8-fold increase in insulin (range, 2.3-117; P < 0.001), a 3.8-fold increase in C-peptide (1.7-32.4; P < 0.001), and a 1.9-fold increase in proinsulin (0.7-5.3, P < 0.001) were detectable whereas NSE and CgA did not increase.
6042 21928201 Adiponectin is a protein produced by the adipose tissue, exhibits potential antiatherogenic properties and is involved in the pathogenesis of insulin resistance.
6043 10077007 Overexpression of IRS-1 led to a 2-fold increase in cell surface GLUT4-HA in cells incubated in the absence of insulin; overexpression of either IRS-3 or IRS-4 elicited a larger increase in cell surface GLUT4-HA.
6044 10077007 Because phosphatidylinositol (PI) 3-kinase is essential for insulin-stimulated translocation of GLUT4, we also studied a mutant IRS-3 molecule (IRS-3-F4) in which Phe was substituted for Tyr in all four YXXM motifs (the phosphorylation sites predicted to bind to and activate PI 3-kinase).
6045 10077007 Our data suggest that IRS-3 and IRS-4 are capable of mediating PI 3-kinase-dependent metabolic actions of insulin in adipose cells, and that IRS proteins play a physiological role in mediating translocation of GLUT4.
6046 11641236 In fact, IRS-1 appears to have its major role in skeletal muscle whereas IRS-2 appears to regulate hepatic insulin action as well as pancreatic beta cell development and survival.
6047 12606503 Here, we show that forkhead transcription factor FKHR contributes to mediating the effects of insulin on PGC-1 promoter activity.
6048 12606503 Reporter assays demonstrate that insulin suppresses the basal PGC-1 promoter activity and that coexpression of protein kinase (PK)-B mimics the effect of insulin in HepG2 cells.
6049 12606503 Insulin response sequences (IRSs) are addressed in the PGC-1 promoter as the direct target for FKHR in vivo.
6050 12606503 These results indicate that signaling via PKB to FKHR can partly account for the effect of insulin to regulate the PGC-1 promoter activity via the IRSs.
6051 18510434 Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis.
6052 18510434 In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin.
6053 22028710 Present therapies to minify hyperglycaemia and insulin resistance mainly target ATP-sensitive K(+) channels (K(ATP)) of pancreatic cells and PPAR-? to enhance the insulin secretion and potential for GLUT expression, respectively.
6054 22028710 Inhibition of CDK5 averts the decrease of insulin gene expression through the inhibition of nuclear translocation of PDX-1 which is a transcription factor for the insulin gene.
6055 9568691 IL-1beta inhibits insulin secretion from pancreatic beta-cells by stimulating the expression of inducible nitric oxide synthase (iNOS) that generates the free radical nitric oxide.
6056 9691088 Treatment of human islets with a combination of tumor necrosis factor (TNF) + lipopolysaccharide (LPS) + interferon-gamma (IFN-gamma) stimulates inducible nitric oxide synthase (iNOS) expression, nitric oxide production, and inhibits glucose-stimulated insulin secretion.
6057 9691088 The IL-1 receptor antagonist protein (IRAP) prevents TNF + LPS + IFN-gamma-induced iNOS expression and nitrite production, and attenuates the inhibitory effects on glucose-stimulated insulin secretion by human islets.
6058 9691088 Inhibition of iNOS activity by aminoguanidine also attenuates TNF + LPS + IFN-gamma-induced inhibition of insulin secretion by human islets.
6059 9691088 These findings support the hypothesis that activated islet macrophages may mediate beta cell damage during the development of insulin-dependent diabetes by releasing IL-1 in human islets followed by cytokine-induced iNOS expression by beta cells.
6060 11211190 We compared insulin secretion, islet cell death and survival, inducible nitric oxide synthase (iNOS) mRNA expression, nitrite production, and Bcl-2 and Bax mRNA expression in isolated human and large mammal (bovine) islets exposed to 50 U/ml recombinant human interleukin-1, 1,000 U/ml recombinant human tumor necrosis factor-alpha and 1,000 U/ml recombinant human interferon-gamma.
6061 11272138 Furthermore, the genetic absence of PKR did not affect dsRNA + IFN-gamma-induced iNOS expression, nitric oxide production, or the inhibitory actions of these agents on glucose-stimulated insulin secretion.
6062 11272138 These results suggest that 1) NF-KB activation is required for dsRNA + IFN-gamma-induced iNOS expression, 2) PKR is not required for either dsRNA-induced NF-kappaB activation or dsRNA + IFN-y-induced iNOS expression by islets, and 3) PKR is not required for dsRNA + IFN-gamma-induced inhibition of glucose-stimulated insulin secretion by islets.
6063 11593036 IL-1beta and IFN-gamma alone, or potentiated by TNF-alpha, are cytotoxic to the insulin producing pancreatic beta-cells and beta-cell lines in vitro and suggested to contribute to the specific beta-cell destruction in Type-1 diabetes mellitus (T1DM).
6064 12031968 The presence of cFLIP prevented the weak TNF-alpha-induced reduction in cellular insulin content and secretion; however, it did not prevent the decrease in glucose-stimulated insulin secretion induced by the combined cytokines, in agreement with our previous data demonstrating that interferon-gamma alone could induce these beta-cell dysfunctions.
6065 12176727 Platelet-derived growth factor (PDGF) increased VSMC migration, which was inhibited by pretreatment with insulin in a dose-dependent manner.
6066 12176727 Insulin also caused a 60% decrease in PDGF-stimulated mitogen-activated protein kinase (MAPK) phosphorylation and activation.
6067 12176727 Insulin inhibition of MAPK was accompanied by a rapid induction of MAPK phosphatase (MKP-1), which inactivates MAPKs by dephosphorylation.
6068 12176727 Pretreatment with inhibitors of the nitric oxide (NO)/cGMP pathway, blocked insulin-induced MKP-1 expression and restored PDGF-stimulated MAPK activation and migration.
6069 12176727 Expression of antisense MKP-1 RNA prevented insulin's inhibitory effect and restored PDGF-directed VSMC migration and MAPK phosphorylation.
6070 12176727 We conclude that insulin inhibition of VSMC migration may be mediated in part by NO/cGMP/cGK Ialpha induction of MKP-1 and consequent inactivation of MAPKs.
6071 12898012 Interleukin-1beta (IL-1beta) has been reported to cause suppression of insulin secretion from pancreatic islets via induction of inducible nitric oxide synthase (iNOS) followed by nitric oxide (NO) production.
6072 12898012 We measured insulin secretion and insulin content of the islets by ELISA, iNOS mRNA expression by reverse transcription-polymerase chain reaction, and NO generation by Griess Reagent System.
6073 15351621 To investigate the role of C-peptide alone or in conjunction with insulin on the expression of nitric oxide synthase (NOS) in human corpus cavernosum smooth muscle cells (HCSMCs).
6074 15351621 Increased expression of eNOS and iNOS was found after treatment with insulin or hrC-peptide alone, and the maximal expression of eNOS and iNOS was detected in HCSMCs exposed to both insulin and hrC-peptide.
6075 15351621 Our results demonstrated that C-peptide, in the presence of insulin, increases the expression of iNOS and eNOS in HCSMCs.
6076 15459112 Treatment of human islets with a combination of IL-1beta and IFN-gamma (IL-1beta+IFN-gamma), for 48 h and 5 d, resulted in an increase of NO production and the impairment of glucose-stimulated insulin secretion, respectively.
6077 19347338 Recent data suggest that the proinsulin cleavage product C-peptide could play a causal role in atherogenesis by promoting monocyte and CD4-positive lymphocyte recruitment in early arteriosclerotic lesions and by inducing the proliferation of vascular smooth muscle cells.
6078 21633404 We analyzed whether common variants in the gene encoding CB1, CNR1, are associated with insulin resistance, risk of type 2 diabetes (T2D) or coronary heart disease (CHD).
6079 21734192 Glucagon-like peptide-1 (GLP-1) elevates intracellular concentration of cAMP ([cAMP]) and facilitates glucose-dependent insulin secretion in pancreatic ?-cells.
6080 21791620 In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition.
6081 21840999 Additionally, when livers were perfused in the absence of insulin, 4E-BP1 phosphorylation in the livers of diabetic mice was normalized to the control value, yet O-GlcNAcylation and the association of 4E-BP1 with eIF4E remained elevated in the liver of diabetic mice.
6082 21869742 Human islets were cultured in medium supplemented with or without GDNF (100 ng/mL) and in vitro islet survival and function assessed by analyzing ?-cell apoptosis and glucose stimulated insulin release.
6083 21896852 The present work shows a melatonin synthesis reduction in diabetic rats retinas associated with a reduction in AANAT activity that was prevented by insulin treatment.
6084 14693422 Thus, members of the SIK family are emerging as important modulators of key processes such as steroid hormone biosynthesis by the adrenal cortex and insulin signaling in adipocytes.
6085 17556363 Direct control of leptin receptor expression by insulin could also be demonstrated in isolated hepatocytes from normal mice.
6086 17556363 Thus, insulin signaling in the liver plays an important role in control of leptin receptor expression and shedding.
6087 17556363 In this manner, insulin signaling in liver plays an important role in leptin homeostasis and fine modulation of leptin action.
6088 18268350 Of 40 identified insulin-induced effectors, 7 have not previously been described in insulin signaling, including SDR, PKCdelta binding protein, LRP-6, and PISP/PDZK11, a potential calcium ATPase binding protein.
6089 21893030 We examined whether vaspin affects the insulin-signaling pathway in cultured endothelial cells and is capable of preventing free fatty acid (FFA)-induced apoptosis in endothelial cells through its insulin sensitizing effect, specifically, through its stimulatory effect on PI3-kinase/Akt signaling pathways.
6090 21893030 Vaspin significantly increased Akt phosphorylation and prevented the impairment of Akt phosphorylation by linoleic acid (LA) in insulin-stimulated endothelial cells, which effects were abolished by pretreatment with the PI3-kinase inhibitor, Wortmannin.
6091 12429837 Inhibition of Src with PP2 blocks the ability of insulin to sequester beta(2)-adrenergic receptors and the translocation of the GLUT4 glucose transporters.
6092 12502489 Using PTP1B antisense oligonucleotides (ASOs), effects of decreased PTP1B levels on insulin signaling in diabetic ob/ob mice were examined.
6093 12502489 Protein kinase B (PKB) serine phosphorylation was increased sevenfold in liver of PTP1B ASO-treated mice upon insulin stimulation, while phosphorylation of PKB substrates, glycogen synthase kinase (GSK)-3alpha and -3beta, was increased more than twofold.
6094 12502489 These results indicate that reduction of PTP1B is sufficient to increase insulin-dependent metabolic signaling and improve insulin sensitivity in a diabetic animal model.
6095 12502490 The activation of the downstream kinase Akt/PKB by insulin, assessed by in vitro kinase assay and phosphorylation of GSK-3beta, were also impaired in muscle of high-fat-fed rats consuming casein or soy protein, but these defects were also fully prevented by dietary cod protein.
6096 12502490 Normalization of PI 3-kinase/Akt activation by insulin in rats fed high-fat diets with cod protein was associated with improved translocation of GLUT4 to the T-tubules but not to the plasma membrane.
6097 12502490 Taken together, these results show that dietary cod protein is a natural insulin-sensitizing agent that appears to prevent obesity-linked muscle insulin resistance by normalizing insulin activation of the PI 3-kinase/Akt pathway and by selectively improving GLUT4 translocation to the T-tubules.
6098 12684506 Furthermore, we examined the effect of L-PGDS incubation on insulin-stimulated Akt, glycogen synthase kinase-3beta (GSK-3beta), and ERK phosphorylation.
6099 12684506 Unexpectedly, we found that when WKY cells were pretreated with L-PGDS, insulin could actually induce apoptosis and failed to stimulate Akt/GSK-3beta phosphorylation.
6100 12684506 Insulin-stimulated ERK phosphorylation was unaffected by L-PGDS pretreatment in both cell lines.
6101 14623899 Replacing Ser(302) with alanine significantly reduced insulin-stimulated tyrosine phosphorylation of IRS-1 and p85 binding and reduced insulin-stimulated phosphorylation of p70(S6K), ribosomal S6 protein, and 4E-BP1; however, this mutation had no effect on insulin-stimulated Akt or glycogen synthase kinase 3beta phosphorylation.
6102 15194499 In myotubes established from type 2 diabetic and healthy control subjects we determined GS activity ratio, protein expression, and activity of GSK-3alpha and beta under basal and insulin-stimulated conditions when precultured in increasing insulin concentrations.
6103 15194499 In myotubes precultured at low insulin concentrations acute insulin stimulation increased GS activity more in control than in diabetic subjects, whereas the corresponding GSK-3alpha but not GSK-3beta activity was significantly reduced by acute insulin treatment in both groups.
6104 15793248 We show here that dexamethasone upregulates transcription and expression of the serum- and glucocorticoid-inducible kinase 1 (SGK1) in insulin-secreting cells, an effect reversed by mifepristone (RU486), an antagonist of the nuclear glucocorticoid receptor.
6105 16443776 Phosphatidylinositol 3-kinase (PI3 kinase) inhibition disrupts the ability of insulin to stimulate GLUT1 and GLUT4 translocation into the cell membrane and thus glucose transport.
6106 16478782 In skeletal muscle, both insulin and exercise decrease GSK-3beta activity, and we tested the hypothesis that these two stimuli regulate beta-catenin.
6107 16478782 In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle beta-catenin phosphorylation or Dvl-GSK-3beta interaction.
6108 16478782 In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3beta in skeletal muscle, an event paralleled by beta-catenin dephosphorylation.
6109 16839840 Insulin increased (P < .05) Akt Ser473 and GSK-3alpha/beta Ser21/Ser9 phosphorylation in both trials, with the response tending to be higher in the exercise trial.
6110 16960890 In parental HepG2 cells, TNF-alpha treatment for 24 h reduced the phosphorylation of Akt1/PKB-alpha and GSK-3beta and under these conditions cells also showed reduced insulin responsiveness in terms of Akt1/PKB-alpha and GSK-3beta phosphorylation.
6111 16960890 In order to understand the reason for the differential insulin resistance in both the cell types, the effect of long-term TNF-alpha treatment on the proteins upstream to Akt/PKB was investigated.
6112 16960890 TNF-alpha pre-incubation also showed reduced insulin-stimulated Tyr phosphorylation of insulin receptor (IR-beta) in both the cell types, moreover hyperphosphorylation of IRS-1 at Ser 312 residue was observed in TNF-alpha pre-incubated cells.
6113 16960890 As hyperphosphorylation of IRS-1 at Ser 312 can induce its degradation, it is possible that reduced insulin responsiveness after long-term TNF-alpha pre-incubation observed in this study is due to the decrease in IRS-1 levels.
6114 17021050 These data indicate distinct roles for Akt-1 and Akt-2 in muscle glucose metabolism and that moderate reductions in IRS-1 expression do not result in the development of insulin resistance in skeletal muscle in vivo.
6115 17223256 However, the expected functional consequences were not observed, as we saw no change in basal or insulin-stimulated glucose uptake and phosphorylation of GSK3beta, Akt (T308 and S473) or ERK1/2.
6116 18534819 The decreased ATM expression suggests that ATM is involved in the development of insulin resistance through down-regulation of Akt activity.
6117 18534819 An immunofluorescence experiment demonstrated that in L6 cells transfected with wild-type (WT) ATM, insulin caused a dramatic increase of the cell surface glucose transporter 4 (GLUT4), while in cells transfected with kinase-dead (KD) ATM, translocation of GLUT4 to the cell surface in response to insulin was markedly inhibited.
6118 18606491 Glycogen synthase kinase 3beta (GSK3beta), a multifunctional serine/threonine kinase found in all eukaryotes, had been initially identified as a key regulator of insulin-dependent glycogen synthesis.
6119 18694957 Mice engineered to lack GSK-3beta die in late embryogenesis from liver apoptosis, whereas mice engineered to lack GSK-3alpha are viable and exhibit improved insulin sensitivity and hepatic glucose homeostasis.
6120 18701453 We tested the hypothesis that inactivation of glycogen synthase kinase 3beta (GSK3beta) by high glucose and high insulin induces increase in synthesis of laminin beta1 via activation of eIF2Bepsilon.
6121 18701453 High glucose and high insulin augmented activation of Akt, Erk, and p70S6 kinase.
6122 18985156 Serum- and Glucocorticoid-inducible Kinase 1 (SGK1) is involved in the regulation of insulin secretion and may represent a candidate gene for the development of type 2 diabetes mellitus in humans.
6123 19365404 PTEN, a negative regulator of the phosphatidylinositol-3-kinase/AKT pathway, is an important modulator of insulin signaling.
6124 19365404 To investigate the mechanism for the resistance to HFD-induced hyperglycemia in PPKO mice, we evaluated AKT phosphorylation in major insulin-responsive tissues: the liver, muscle, and fat.
6125 19472218 We have also shown that inhibition of tyrosine kinase activity of insulin receptor (IR) and/or insulin-like growth factor 1 (IGF1) receptor (IGFR) reverses the PLTP-induced increase in levels of phosphorylated Akt (pAkt(Thr308) and pAkt(Ser473)), suggesting that PLTP-mediated activation of the PI3K/Akt pathway is dependent on IR/IGFR receptor tyrosine kinase activity.
6126 19808894 IkappaB kinase-(IKK)-beta inhibition prevented mitogen-activated protein (MAP) kinase kinase (MEK)/ERK1/2 activation in response to interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha but not insulin in 3T3-L1 and human adipocytes, suggesting that IKKbeta regulated a MAP kinase kinase kinase (MAP3K) involved in ERK1/2 activation induced by inflammatory cytokines.
6127 20004975 We found that insulin alone stimulates tyrosine phosphorylation of tyrosine kinases Lyn, Syk, Fyn, the adapter protein Gab2 (Grb2-associated binding protein 2), Akt and activates ERK, JNK and p38 kinase.
6128 20004975 Effect of insulin on FcepsilonRI signaling pathways was marked by enhanced phosphorylation of Lyn, Fyn, Gab2 and Akt.
6129 20004975 Furthermore, BMMC stimulated with antigen in the presence of insulin responded with enhanced protein kinase theta (PKCtheta) activity and increased JNK phosphorylation when compared to BMMC triggered with antigen alone.
6130 20021289 SGK1 is activated by insulin and growth factors via the phosphatidylinositol-3-kinase pathway.
6131 20232313 Mesenchymal transition and concomitant losses in insulin gene expression observed on C-IV were found to be dependent on beta(1)-integrin ligation and were augmented in the presence of hepatocyte growth factor.
6132 20232313 Importantly, selective inhibition of c-Src, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) prior to exposure to C-IV prevented mesenchymal transition and effectively preserved insulin expression.
6133 20384568 No previous study has investigated how the vaso-constrictive peptide Ang II impacts insulin action in isolated mammalian skeletal muscle.
6134 20384568 Soleus strips were incubated with insulin (5 mU/ml) and/or Ang II (500 nM) for 2 hours.
6135 20384568 Ang II caused significant (p < 0.05) inhibition of insulin-stimulated glucose transport (39%) and decreased phosphorylation of Akt Ser(473) (37%) and glycogen synthase kinase-3beta Ser(9) (42%) without affecting phosphorylation of IRS-1 Ser(307) or p38 MAPK.
6136 20384568 We used the superoxide dismutase mimetic, tempol (1 mM), to determine if reactive oxygen species (ROS) contribute to Ang II-mediated insulin resistance.
6137 20604929 Analysis of insulin signalling revealed renal-specific upregulation of PKBbeta/Akt2, hyperphosphorylation of GSK3beta and concomitant accumulation of beta-catenin in Irs2-/- kidney.
6138 21817126 We have previously reported that insulin protects ? cells from apoptosis and promotes proliferation by activating Raf-1 signaling in cultured human islets, mouse islets, and MIN6 cells.
6139 21817126 As Raf-1 activity is critical for basal apoptosis and insulin secretion in vitro, we hypothesized that Raf-1 may play an important role in glucose homeostasis in vivo.
6140 21817126 RIPCre(+/+):Raf-1(flox/flox) mice had increased fasting blood glucose levels and impaired glucose tolerance but normal insulin tolerance compared to littermate controls.
6141 21817126 This work provides the first direct evidence that Raf-1 signaling is essential for the regulation of basal insulin transcription and the supply of releasable insulin in vivo.
6142 21885493 Spearman correlations and multivariable regressions were used to examine whether resistin levels were associated with SLE, disease-specific and inflammatory markers, insulin resistance, and CAC.
6143 21885493 Resistin level did not correlate with markers of insulin resistance or body adiposity, including homeostatic model assessment or BMI.
6144 21885493 Among subjects with SLE, higher resistin level correlated positively with renal dysfunction, inflammatory markers, and disease damage but not with insulin resistance or BMI.
6145 21965330 This oxidative stress disrupted mTorc2 and impaired mTorc2/Akt signaling in other insulin-sensitive organs, leading to insulin resistance that could be largely reversed with antioxidant treatment.
6146 21985785 Here, we have demonstrated that CR increases Sirt1 deacetylase activity in skeletal muscle in mice, in parallel with enhanced insulin-stimulated phosphoinositide 3-kinase (PI3K) signaling and glucose uptake.
6147 21985785 Mechanistically, Sirt1 was found to be required for the deacetylation and inactivation of the transcription factor Stat3 during CR, which resulted in decreased gene and protein expression of the p55?/p50? subunits of PI3K, thereby promoting more efficient PI3K signaling during insulin stimulation.
6148 21985785 Thus, these data demonstrate that Sirt1 is an integral signaling node in skeletal muscle linking CR to improved insulin action, primarily via modulation of PI3K signaling.
6149 22044999 Here we show that mice with EpoR expression restricted to haematopoietic tissues (Tg) develop obesity and insulin resistance.
6150 22044999 This study provides the first evidence that mice lacking EpoR in non-haematopoietic tissue become obese and insulin resistant with loss of Epo regulation of energy homeostasis.
6151 22045262 Inhibition of Ucp2, in isolated islets, leads to a rescue of the glucose-induced ATP production and insulin secretion in Bmal1-/- islets.
6152 22046277 The changes in plasma FGF-21 levels (?FGF-21) were positively associated with the amelioration of insulin resistance shown by the changes in M value.
6153 15619630 Gut polypeptides secreted in response to food intake, such as glucagon-like peptide-1 (GLP-1), are potent incretin hormones that enhance the glucose-dependent secretion of insulin from pancreatic beta cells.
6154 21624209 Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple epiphyseal dysplasia and growth retardation, and other variable multisystem clinical manifestations.
6155 21874001 SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively).
6156 21995154 Resistin is a potent regulator of glucose homeostasis which is thought to oppose the action of insulin in peripheral tissues.
6157 18466760 Taken together, our data suggest that ASIC3 signaling might be involved in the control of age-dependent glucose intolerance and insulin resistance.
6158 19088165 Osteocalcin has been reported to contribute to the regulation of glucose tolerance and insulin secretion and sensitivity in experimental animals.
6159 19088165 In cross-sectional analyses (baseline data), we estimated the associations of serum osteocalcin and urine N-telopeptide with markers of metabolic phenotype including fasting plasma glucose (FPG) (primary outcome), fasting insulin, insulin sensitivity estimated by homeostasis model assessment for insulin resistance, plasma high-sensitivity C-reactive protein, IL-6, and measures of adiposity (BMI and body fat) (secondary outcomes) after multivariate adjustment for potential confounders.
6160 21946084 The cellular results showed that insulin suppressed disaccharidase activities and down-regulated SI complex and Cdx2 mRNA expression in a concentration-dependent manner.
6161 21986529 In addition, chromatin immunoprecipitation analysis demonstrated that both tunicamycin treatment and ATF3 overexpression inhibited the recruitment of p300 to PDX-1 on the insulin promoter in MIN6N8 cells.
6162 22053613 We investigated the association of TNF-alpha and CXCL-10 with insulin resistance in HCV infected patients.
6163 21873205 This effect is mimicked by knockdown of Sirt3 in cultured myoblasts, which exhibit reduced mitochondrial oxidation, increased reactive oxygen species, activation of JNK, increased serine and decreased tyrosine phosphorylation of IRS-1, and decreased insulin signaling.
6164 21873226 These effects coincided with activation of leptin and insulin signaling pathways and down-regulation of the PKR-like endoplasmic reticulum (ER) kinase/eukaryotic translation inhibition factor 2? (PERK-eIF2?) arm of ER stress in liver, skeletal muscle, and adipose tissue as well as increased pro-opiomelanocortin and decreased agouti-related peptide in the hypothalamus.
6165 21901280 TCF7L2 silencing did not affect the half-maximal inhibitory concentration of insulin or metformin, but HGP remained elevated in TCF7L2-silenced cells due to the increased baseline HGP.
6166 21965021 We show for the first time that TRAIL deficiency promotes numerous features of diabetes that are typical of human disease, and are associated with reduced insulin and pancreatic inflammation/apoptosis.
6167 22015196 YQZM formula can enhance GLUT4 translocation from the cytoplasm to the plasma membrane in skeletal muscle tissues, and displays the insulin sensitization characteristic of rosiglitazone.
6168 22037645 Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion.
6169 22037645 Here we show that administration of IL-6 or elevated IL-6 concentrations in response to exercise stimulate GLP-1 secretion from intestinal L cells and pancreatic alpha cells, improving insulin secretion and glycemia.
6170 22037645 Hence, IL-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand.
6171 22037645 This previously unidentified endocrine loop implicates IL-6 in the regulation of insulin secretion and suggests that drugs modulating this loop may be useful in type 2 diabetes.
6172 21854074 The free fatty acid receptor 1 (FFA1, also known as GPR40) enhances glucose-stimulated insulin secretion from pancreatic ?-cells and is recognized as an interesting new target for treatment of type 2 diabetes.
6173 21969604 Insulin increased 14-3-3 binding to RhoGAP22 fourfold, and this effect was PI3K dependent.
6174 21969604 We propose that insulin and possibly growth factors such as platelet-derived growth factor may play a novel role in regulating cell migration and motility via the Akt-dependent phosphorylation of RhoGAP22, leading to modulation of Rac1 activity.
6175 21973233 Fasting serum FGF-21 was found to correlate positively and significantly with age, waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, glycosylated hemoglobin A1c, homeostasis model assessment (HOMA) of insulin resistance, and hsCRP, but negatively with HOMA of ?-cell insulin secretion.
6176 22067655 These findings suggest that downregulation of AMPK precedes mTOR/p70S6K activation in mediating glucose and leucine-induced insulin resistance, although the mechanism by which it does so remains to be determined.
6177 21750828 We propose a unified model of extra- and intracellular mechanisms of anti-diabetic efficacies of V(v/iv), Mo(vi), W(vi), and Cr(iii), centred on high-oxidation-state oxido/peroxido species that inhibit protein tyrosine phosphatases (PTPs) involved in insulin signalling.
6178 21885675 Lipocalin 2 (LCN2 or NGAL), a protein derived from neutrophils, macrophages, adipocytes, and other cells, has been proposed to be a link between obesity and insulin resistance (IR), but animal and cross-sectional human studies have revealed conflicting results.
6179 21294959 In contrast, in older P1-Ngn3Cre mice the relative increase of the pancreatic insulin content exceeded that of somatostatin and these mice remained normoglycemic.
6180 21949050 Thus, we reinvestigated the impact of small heterodimer partner (SHP) deletion on diet-induced obesity and insulin resistance using congenic SHP(-/-) mice.
6181 22074575 One of the key metabolic actions of insulin is to control blood sugar levels by promoting glucose uptake into adipocyte and muscle cells.
6182 22078880 The dominant function of adipocyte NCoR is to transrepress PPAR? and promote PPAR? ser-273 phosphorylation, such that NCoR deletion leads to adipogenesis, reduced inflammation, and enhanced systemic insulin sensitivity, phenocopying the TZD-treated state.
6183 17259374 Interestingly, MCH enhanced insulin secretion in human and mouse islets and rodent beta-cell lines in a dose-dependent manner.
6184 21640361 Nebivolol treatment for 3 weeks reduces NADPH oxidase activity and improves systemic insulin resistance in concert with reduced oxidative stress in skeletal muscle in a young rodent model of hypertension, insulin resistance, and enhanced tissue RAS expression.
6185 21874366 The rats were followed for 6 weeks after surgery, and their body weight change, cumulative food intake, metabolic parameters, plasma levels of ghrelin, glucagon-like peptide-1 and adiponectin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and gastric emptying rate were measured.
6186 21881539 To identify these mechanisms, we studied the effect of ACE-inhibition on gene expression in skeletal muscle, a primary target tissue for insulin in glucose homeostasis.
6187 21885477 Activation of GPR55 by the agonist O-1602 increased calcium transients (P<0.01) and insulin secretion (P<0.001) stimulated by glucose.
6188 21885477 Indeed, acute in vivo experiments showed that GPR55 activation increases glucose tolerance (P<0.05) and plasma insulin levels (P<0.05), suggesting an in vivo physiological relevance of GPR55 systemic stimulation.
6189 21295959 Lactoferrin has been associated with insulin sensitivity in vivo and in vitro studies.
6190 21295959 The response to insulin was evaluated through (Ser473)AKT phosphorylation.
6191 21295959 In both subcutaneous and visceral preadipocytes, lactoferrin (1 and 10 ?M) increased adipogenic gene expressions and protein levels (fatty acid synthase, PPAR?, FABP4, ADIPOQ, ACC and STAMP2) and decreased inflammatory markers (IL8, IL6 and MCP1) dose-dependently in parallel to increased insulin-induced (Ser473)AKT phosphorylation.
6192 21295959 In conclusion, these results suggest that lactoferrin promotes adipogenesis in human adipocytes by enhancing insulin signaling and inhibiting RB1 and AMPK activities.
6193 21615395 Basal PPARD, PDK4 and ANGPTL4 expression levels were not associated with donors' insulin sensitivity (P?>?0·2, all).
6194 21615395 However, GW501516-mediated fold increments in PDK4 and ANGPTL4 expression, reflecting PPAR? responsiveness, were positively associated with donors' insulin sensitivity derived from OGTT (P?=?0·0182 and P?=?0·0231, respectively) and hyperinsulinemic-euglycemic clamp (P?=?0·0046 and P?=?0·0258, respectively).
6195 21840935 Among participants with both hypertension and insulin resistance, there was a significant direct association between adiponectin and the LVM index after multivariable adjustment (?=1.55, P=0.04, per 1-SD increment in the adiponectin log value).
6196 21840935 Conclusions- The association between serum adiponectin and LVM among blacks in the Jackson Heart Study cohort was dependent on hypertension and insulin resistance status.
6197 21871685 Thus, early intensive insulin therapy can increase serum adiponectin and NO concentrations and improve endothelial function in patients with newly diagnosed T2DM.
6198 21939653 Karanjin-induced GLUT4 translocation was further enhanced with insulin and the effect is completely protected in the presence of wortmannin.
6199 21967816 Importantly, pyruvate kinase M2, a fetal anabolic enzyme implicated in the Warburg effect, was activated by insulin in vivo and in vitro.
6200 21998599 In vitro binding experiments showed that tomosyn-2 binds recombinant syntaxin-1A and syntaxin-4, key proteins that are involved in insulin secretion via formation of the SNARE complex.
6201 22086011 Continual high-fat diet powerfully stimulated GIP secretion,leading to obesity and harmful lipid deposition in islet cells and peripheral tissues,and giving rise to insulin resistance and major disturbances in the secretion of insulin.
6202 22087278 AMG 837 was a potent partial agonist in the calcium flux assay on the GPR40 receptor and potentiated glucose stimulated insulin secretion in vitro and in vivo.
6203 22087313 Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired.
6204 22087313 Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3?.
6205 21396419 Ghrelin plays an important physiological role in modulating GH secretion, insulin secretion and glucose metabolism.
6206 21396419 Pharmacological suppression of the ghrelin/des-acyl ghrelin ratio by treatment with des-acyl ghrelin may also be a viable alternative approach which appears to improve insulin sensitivity.
6207 21939650 Plasma visfatin and RBP-4 concentrations correlated with BMI, waist/hip ratio, insulin and homeostatic model assessment insulin resistance (HOMA(IR)).
6208 21939650 Plasma RBP-4 correlated positively with liver fat and HOMA(IR) which may reflect its effects on hepatic insulin sensitivity.
6209 22043012 Glyphosine, a pocket 9 compound, enhances insulin peptide presentation to T cells at concentrations as low as 10 nM, upregulates IL-10 secretion, and prevents diabetes in NOD mice.
6210 21437630 TCF7L2 and SLC30A8 have been found to be associated with type 2 diabetes mellitus (T2DM) as well as with impaired proinsulin processing recently, enzymes encoded by PCSK1 and PCSK2 are reported to play an important role in the process of proinsulin conversion.
6211 21437630 To investigate whether the single nucleotide polymorphisms (SNPs) of TCF7L2, SLC30A8, PCSK1 and PCSK2 were associated with T2DM as well as with proinsulin conversion in a Han Chinese population from Chongqing.
6212 21437630 Rs13266634 at SLC30A8 had a tendency to be associated with fasting plasma levels of proinsulin (P = 0.0639 in additive model).
6213 22007192 In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndrome in vivo including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver.
6214 21709540 This work indicates the potential link of ATGL with the pathogenesis of insulin resistance and T2DM.
6215 21880378 At a cellular level, angiotensin II (Ang II) and aldosterone induce insulin resistance by increasing oxidative stress and altering insulin signaling, leading to decreased glucose transport.
6216 21984580 TIMP3 was also reduced, along with insulin resistance, resulting in increased ectodomain shedding activity of the metalloprotease ADAM17.
6217 21984584 In contrast, GIP increases glucagon levels during fasting and hypoglycemic conditions, where it has little or no effect on insulin secretion.
6218 21994424 OBJECTIVE To assess the efficacy and safety of MK-0941, a glucokinase activator (GKA), when added to stable-dose insulin glargine in patients with type 2 diabetes.
6219 21998398 Our data support the hypothesis that insulin therapy may contribute to the expansion of autoreactive CD8(+) T cells in the long term.
6220 21998399 Silent information regulator 1 (SIRT1), an NAD-dependent protein deacetylase, is involved in insulin secretion.
6221 21998399 SIRT1 is required for the improved insulin transcription, secretion, and resistance to STZ-induced hyperglycemia caused by Wld(S).
6222 21998402 OBJECTIVE Increase in adipose cAMP-responsive elementx{2013}binding protein (CREB) activity promotes adipocyte dysfunction and systemic insulin resistance in obese mice.
6223 21998402 CONCLUSIONS Impaired expression of ICER contributes to elevation in CREB target genes and, therefore, to the development of insulin resistance in obesity.
6224 22013013 RESULTS Despite similar insulin and glucose concentrations during the clamp, activation of B2AR in the VMH significantly lowered by 32% (P < 0.01), whereas VMH B2AR blockade raised by 27% exogenous glucose requirements during hypoglycemia (P < 0.05) compared with the control study.
6225 22065673 In nonobese diabetic (NOD) mice, two sets of autoreactive CD4(+) T cells recognize the B:9-23 segment of the insulin B chain.
6226 21697213 Repeated application of EA is capable of improving diet-induced insulin resistance, probably through activation of AMPK signalling pathways in skeletal muscle.
6227 21952242 Feeding a high-lactose calcium rescue diet that circumvents a VDR requirement for calcium absorption from the intestine normalized serum calcium levels, restored ?-cell insulin secretion, corrected glucose intolerance, and eliminated accelerated T1D in VDR-deficient NOD mice.
6228 22112254 GLP-1 and GIP are released in response to food ingestion; they enhance nutrient-induced insulin secretion and inhibit postprandial glucagon secretion.
6229 22113197 Overexpression of MSI1 was sufficient to increase Hes1, stimulate proliferation, inhibit apoptosis and reduce insulin expression, whereas Msi1 knockdown had the converse effects on proliferation and insulin expression.
6230 22113197 Taken together, these results demonstrate overlapping, but distinct roles for Musashi-1 and Musashi-2 in the control of insulin expression and ?-cell proliferation.
6231 21550077 The plasma levels of glucose, insulin, growth hormone, free IGF-I, total IGF-I (associated to insulin-like growth factor binding proteins plus free), and corticosterone were measured in 13-week-old ZDF rats and in age-matched controls under fasting and postprandial conditions.
6232 21711391 Previously reported association between MTNR1B variants (rs10830963, rs4753426) and oral glucose tolerance test-derived indices of ?-cell function (homeostasis model assessment-B, P = 3.7 × 10?? and P = 0.004, respectively), as well as insulin (fasting insulin: P=2×10?³ and P=0.02; 30-min insulin: P = 2.1 × 10?? and P=0.03, respectively) and fasting glucose (rs10830963, P=1.2×10??) parameters could be replicated in the present study.
6233 21919686 This study also established that SNP in intron 1 of FTO (rs17817449) are strongly associated with several measures of adiposity and are also associated with plasma insulin, insulin resistance, percentage body fat and fat mass.
6234 21969371 Mimicking this, islets from PAK1(-/-) knock-out mice exhibited profound defects in the second/sustained-phase of insulin secretion.
6235 21969371 Exacerbating this, the PAK1(-/-) knock-out mice also exhibited peripheral insulin resistance.
6236 21969371 Insulin resistance was coupled to ablation of insulin-stimulated GLUT4 translocation in skeletal muscle from PAK1(-/-) knock-out mice, and in sharp contrast to islet beta cells, skeletal muscle PAK1 loss was underscored by defective cofilin phosphorylation but normal ERK1/2 activation.
6237 21990351 Hepatic IRS2 protein was dramatically up-regulated in mice treated with T863, possibly contributing to improved insulin sensitivity.
6238 21990351 In differentiated 3T3-L1 adipocytes, T863 enhanced insulin-stimulated glucose uptake, suggesting a possible role for adipocytes to improve insulin sensitivity upon DGAT1 inhibition.