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Gene Information

Gene symbol: IGFALS

Gene name: insulin-like growth factor binding protein, acid labile subunit

HGNC ID: 5468

Synonyms: ALS

Related Genes

# Gene Symbol Number of hits
1 AAVS1 1 hits
2 ACTB 1 hits
3 AGXT 1 hits
4 AKT1 1 hits
5 ALB 1 hits
6 ALPI 1 hits
7 ALS2 1 hits
8 ANXA7 1 hits
9 AQP6 1 hits
10 ATP6V1A 1 hits
11 BDNF 1 hits
12 BRCA1 1 hits
13 CAPN6 1 hits
14 CD44 1 hits
15 CDKN1C 1 hits
16 CENPB 1 hits
17 CGA 1 hits
18 CGB 1 hits
19 COL1A1 1 hits
20 CREB1 1 hits
21 CREBBP 1 hits
22 CSF1 1 hits
23 CTGF 1 hits
24 CYP7A1 1 hits
25 DDIT3 1 hits
26 DPP4 1 hits
27 DYNC1H1 1 hits
28 EFNB2 1 hits
29 EIF4A2 1 hits
30 ENSA 1 hits
31 FOS 1 hits
32 FSHB 1 hits
33 GCK 1 hits
34 GEM 1 hits
35 GFER 1 hits
36 GHR 1 hits
37 GPR180 1 hits
38 HIST1H2BO 1 hits
39 HIST2H2BE 1 hits
40 HSPG2 1 hits
41 IDDM13 1 hits
42 IDDM2 1 hits
43 IGF1 1 hits
44 IGF2 1 hits
45 IGFBP1 1 hits
46 IGFBP2 1 hits
47 IGFBP3 1 hits
48 IGFBP4 1 hits
49 IGFBP5 1 hits
50 IGFBP6 1 hits
51 IGFBP7 1 hits
52 IL11 1 hits
53 IL2 1 hits
54 IL6 1 hits
55 INS 1 hits
56 IRS1 1 hits
57 IRS2 1 hits
58 KISS1 1 hits
59 LEP 1 hits
60 M6PR 1 hits
61 MDK 1 hits
62 MLL 1 hits
63 MLL3 1 hits
64 MLLT3 1 hits
65 MMP1 1 hits
66 MMP9 1 hits
67 NR3C1 1 hits
68 PCK2 1 hits
69 PDPK1 1 hits
70 PEG10 1 hits
71 PKLR 1 hits
72 PPARA 1 hits
73 PPP2R1A 1 hits
74 PRKAA1 1 hits
75 PRL 1 hits
76 PTH 1 hits
77 RHOD 1 hits
78 RXRA 1 hits
79 SDHC 1 hits
80 SERPINE1 1 hits
81 SHBG 1 hits
82 SLC2A4 1 hits
83 SLC37A4 1 hits
84 SLC9A3R2 1 hits
85 SMARCA1 1 hits
86 SP1 1 hits
87 SPARC 1 hits
88 SST 1 hits
89 STAT5A 1 hits
90 TAT 1 hits
91 TGFA 1 hits
92 TGFB1 1 hits
93 TGM2 1 hits
94 TNF 1 hits
95 TP63 1 hits
96 TSHB 1 hits
97 VEGFA 1 hits
98 WNT10B 1 hits

Related Sentences

# PMID Sentence
1 1281986 Post-transcriptional regulation of insulin-like growth factor binding protein-2 mRNA in diabetic rat liver.
2 1281986 IGFBP-1 and IGFBP-2 mRNAs are increased in the livers of streptozotocin-diabetic rats.
3 1281986 A corresponding increase is observed in transcription of the IGFBP-1 but not the IGFBP-2 gene, indicating that the increase in steady-state levels of IGFBP-2 mRNA is a post-transcriptional effect.
4 1281986 IGFBP-1 and IGFBP-2 mRNAs also differ in the rapidity of their response to insulin treatment: hepatic IGFBP-1 mRNA is normalized within 1 h, IGFBP-2 mRNA decreases more slowly.
5 1281986 These differences suggest that IGFBP-2 may provide more chronic adaptation to metabolic change than IGFBP-1.
6 1283442 Insulin rapidly decreases insulin-like growth factor-binding protein-1 gene transcription in streptozotocin-diabetic rats.
7 1283442 Insulin-like growth factor-binding protein-1 (IGFBP-1) can inhibit or potentiate IGF action.
8 1283442 Similarly, IGFBP-1 mRNA is increased in the liver of severely diabetic and ketotic rats and decreased after 4 days of insulin treatment.
9 1283442 Insulin rapidly decreases IGFBP-1 mRNA and IGFBP-1 transcription in rat hepatoma cells.
10 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.
11 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.
12 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.
13 1283442 Normalization of hepatic IGFBP-1 mRNA in insulin-treated diabetic animals did not require restoration of euglycemia.
14 1283442 We propose that the dynamic regulation of IGFBP-1 gene transcription in diabetes and after insulin treatment, by determining the availability of IGFBP-1 in tissues and plasma, may be a critical factor in the modulation of IGF action.
15 1283442 Insulin rapidly decreases insulin-like growth factor-binding protein-1 gene transcription in streptozotocin-diabetic rats.
16 1283442 Insulin-like growth factor-binding protein-1 (IGFBP-1) can inhibit or potentiate IGF action.
17 1283442 Similarly, IGFBP-1 mRNA is increased in the liver of severely diabetic and ketotic rats and decreased after 4 days of insulin treatment.
18 1283442 Insulin rapidly decreases IGFBP-1 mRNA and IGFBP-1 transcription in rat hepatoma cells.
19 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.
20 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.
21 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.
22 1283442 Normalization of hepatic IGFBP-1 mRNA in insulin-treated diabetic animals did not require restoration of euglycemia.
23 1283442 We propose that the dynamic regulation of IGFBP-1 gene transcription in diabetes and after insulin treatment, by determining the availability of IGFBP-1 in tissues and plasma, may be a critical factor in the modulation of IGF action.
24 1378724 Human insulin-like growth factor binding protein-6 is O-glycosylated.
25 1378724 Insulin-like growth factor binding protein-6 is abundant in cerebrospinal fluid and has a marked preferential binding affinity for IGF-II over IGF-I.
26 1378724 Enzymatic deglycosylation did not alter the high affinity of IGF binding protein-6 for IGF-II (Ka 4.4 +/- 2.2 x 10(11) M-1) or its preference for IGF-II over IGF-I.
27 1378724 Human insulin-like growth factor binding protein-6 is O-glycosylated.
28 1378724 Insulin-like growth factor binding protein-6 is abundant in cerebrospinal fluid and has a marked preferential binding affinity for IGF-II over IGF-I.
29 1378724 Enzymatic deglycosylation did not alter the high affinity of IGF binding protein-6 for IGF-II (Ka 4.4 +/- 2.2 x 10(11) M-1) or its preference for IGF-II over IGF-I.
30 1379675 Expression of hepatic insulin-like growth factor-I and insulin-like growth factor-binding protein-1 genes is transcriptionally regulated in streptozotocin-diabetic rats.
31 1379675 Insulin-like growth factor-I (IGF-I) and IGF-binding protein-1 (BP-1) are critical cell regulators, with regulation and action in endocrine, paracrine, and autocrine modes.
32 1379675 Although IGF-I and BP-1 are thought to be modulated mainly at the level of synthesis, underlying molecular mechanisms are poorly understood.
33 1379675 To examine regulation by insulin, we used run-on assays to measure IGF-I and BP-1 gene transcription rates in nuclei isolated from the livers of normal and diabetic rats.
34 1379675 Diabetic animals also had a 45% reduction in hepatic IGF-I mRNA and over 400% increases in BP-1 mRNA (both P less than 0.005); all parameters were restored toward normal after treatment with insulin.
35 1379675 Metabolically responsive IGF-I gene transcription was evaluated effectively with a 3.2-kilobase BglII/EcoRI genomic probe located down-stream from all initiation sites in exon 1, while BP-1 gene transcription was studied with a cDNA probe.
36 1379675 Animals treated with 144 mg/kg STZ exhibited 50-97% decreases in IGF-I gene transcription (P less than 0.05), while insulin treatment raised IGF-I gene transcription to control levels (P less than 0.02).
37 1383070 Elevated plasma insulin-like growth factor binding protein-1 levels in type 1 (insulin-dependent) diabetic patients with peripheral neuropathy.
38 1383070 Since insulin-like growth factor I (IGF-I) has been shown to stimulate nerve regeneration, and IGF binding protein-1 is acutely regulated by plasma insulin we have investigated the relationships between plasma IGF-I, IGFBP-1, glucose and insulin in Type 1 (insulin-dependent) diabetic patients with peripheral polyneuropathy.
39 1383070 Comparison of areas under the curves revealed significant negative correlations between IGFBP-1 and glucose (-0.88, p = 0.01), IGFBP-1 and insulin (-0.75, p = 0.016), and IGFBP-1 and IGF-I (-0.68, p = 0.03).
40 1383070 A significant positive correlation was found between insulin and IGF-I (+0.89, p = 0.001).
41 1383070 The diabetic patients had markedly elevated plasma IGFBP-1 levels (area under curve, p = 0.01) and lower plasma IGF-I levels (p = 0.033) even though these patients were hyperinsulinaemic throughout the study period.
42 1383692 Transcription of the insulin-like growth factor-binding protein-2 gene is increased in neonatal and fasted adult rat liver.
43 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.
44 1688850 Its identification as the insulin-like growth factor-binding protein.
45 1688850 Amino-terminal sequence analysis of the purified inhibitor suggests that it could be the porcine congener of the 53-kDa subunit of the growth hormone-dependent insulin-like growth factor binding protein (IGF-BP3).
46 1688850 Its identification as the insulin-like growth factor-binding protein.
47 1688850 Amino-terminal sequence analysis of the purified inhibitor suggests that it could be the porcine congener of the 53-kDa subunit of the growth hormone-dependent insulin-like growth factor binding protein (IGF-BP3).
48 1690638 Insulin-like growth factor-binding protein (IGF-BP) inhibition of granulosa cell function: effect on cyclic adenosine 3',5'-monophosphate, deoxyribonucleic acid synthesis, and comparison with the effect of an IGF-I antibody.
49 1690638 The effects of insulin-like growth factor binding proteins (IGF-BPs) purified from porcine follicular fluid on granulosa cell function were examined using serum-free cultures of rat granulosa cells obtained from immature, diethylstilbestrol-treated rats.
50 1690638 Both the so-called GH-dependent (IGF-BP3) and non-GH-dependent (IGF-BP2) proteins dose dependently inhibited granulosa cell estradiol and progesterone production with IC50s of 4.1-7.6 nM for IGF-BP3 and 12.6-12.9 nM for IGF-BP2, the actual value depending upon the steroid being measured.
51 1690638 However, both IGF-BP3 and IGF-BP2 were capable of inhibiting both forskolin- and cholera toxin-stimulated steroidogenesis, confirming that neither compound was competing with FSH for binding to its receptor.
52 1693321 The growth hormone independent insulin-like growth factor-I binding protein BP-28 is associated with serum insulin-like growth factor-I inhibitory bioactivity in adolescent insulin-dependent diabetics.
53 1693321 The relationship between the growth hormone independent insulin-like growth factor binding protein (BP-28) and serum insulin-like growth factor-I (IGF-I) inhibitory bioactivity observed in diabetic serum was investigated in five poorly controlled adolescent type I diabetics.
54 1695341 Insulin-like growth factor 1 and its binding protein 1 during normal and diabetic pregnancies.
55 1695341 Investigations of circulating insulin-like growth factor 1, hPL, and infant size during pregnancy in normal and insulin-dependent diabetic women have yielded conflicting results and have not been analyzed longitudinally.
56 1695341 We studied serial changes in maternal serum insulin-like growth factor 1 levels (measured by radioimmunoassay after acid ethanol extraction) throughout pregnancy in 22 normal women and in 38 with insulin-dependent diabetes.
57 1695341 The diabetic women had significantly lower serum insulin-like growth factor 1 concentrations than normal women throughout pregnancy and after delivery, although the rates of change in both groups of women were similar.
58 1695341 Within-patient analysis showed a significant decrease in serum insulin-like growth factor 1 between 6-12 weeks' gestation and a significant increase between 24-32 weeks, followed by a significant decrease from 36 weeks' gestation to 12 weeks after delivery.
59 1695341 Incremental changes in insulin-like growth factor 1 between 24-32 weeks' gestation correlated significantly with incremental changes in hPL (r = 0.40; P less than .001) and with birth weight (r = 0.37; P less than .01), but not with ultrasound measurements of fetal growth.
60 1695341 The correlation of increments in insulin-like growth factor 1 and birth weight became nonsignificant when the association of hPL with both insulin-like growth factor 1 and birth weight was taken into account.
61 1695341 Neither insulin-like growth factor binding protein 1 (placental protein 12) nor its ratio to insulin-like growth factor 1 showed any association with infant size.
62 1695341 The physiologic changes in maternal serum insulin-like growth factor 1 in pregnant diabetic women do not appear related to the increased birth weight of their infants.
63 1699699 Insulin-like growth factor binding protein-1 levels in diabetic adolescents and their relationship to metabolic control.
64 1699699 Circulating levels of the low molecular weight insulin-like growth factor binding protein-1 (IGFBP-1) are insulin dependent and vary markedly throughout the day.
65 1699699 This fall in IGFBP-1 correlated with pubertal stage (r= 0.68, p less than 0.001) and with fasting insulin levels (r = 0.60, p less than 0.001) which rose with pubertal advancement.
66 1699699 In the diabetic children IGFBP-1 levels also correlated inversely with the 0800 h free insulin level but there was no clear relationship with pubertal development.
67 1699699 Insulin-like growth factor binding protein-1 levels in diabetic adolescents and their relationship to metabolic control.
68 1699699 Circulating levels of the low molecular weight insulin-like growth factor binding protein-1 (IGFBP-1) are insulin dependent and vary markedly throughout the day.
69 1699699 This fall in IGFBP-1 correlated with pubertal stage (r= 0.68, p less than 0.001) and with fasting insulin levels (r = 0.60, p less than 0.001) which rose with pubertal advancement.
70 1699699 In the diabetic children IGFBP-1 levels also correlated inversely with the 0800 h free insulin level but there was no clear relationship with pubertal development.
71 1704481 Molecular cloning of the cDNAs encoding a novel insulin-like growth factor-binding protein from rat and human.
72 1704481 cDNA clones encoding a novel insulin-like growth factor-binding protein (IGFBP) purified from rat serum and human bone cell-conditioned medium have been isolated from rat liver and human placenta, liver, and ovary cDNA libraries.
73 1704481 This protein, now proposed to be named IGFBP-4, contains two extra cysteines compared with the previously characterized IGFBP-1, -2, and -3, but the alignment of the remaining 18 cysteines is conserved across the four IGFBPs.
74 1704481 Molecular cloning of the cDNAs encoding a novel insulin-like growth factor-binding protein from rat and human.
75 1704481 cDNA clones encoding a novel insulin-like growth factor-binding protein (IGFBP) purified from rat serum and human bone cell-conditioned medium have been isolated from rat liver and human placenta, liver, and ovary cDNA libraries.
76 1704481 This protein, now proposed to be named IGFBP-4, contains two extra cysteines compared with the previously characterized IGFBP-1, -2, and -3, but the alignment of the remaining 18 cysteines is conserved across the four IGFBPs.
77 1704485 Dexamethasone stimulates transcription of the insulin-like growth factor-binding protein-1 gene in H4-II-E rat hepatoma cells.
78 1704485 Binding proteins for the insulin-like growth factors (IGFBP) are important modulators of the biological actions of IGF-I and IGF-II.
79 1704485 No stimulation was seen with progesterone, testosterone, IGF-I, or rat GH, whereas insulin gave a small inhibition.
80 1706566 Insulin-like growth factor binding protein measurement: sodium dodecyl sulfate-stable complexes with insulin-like growth factor in serum prevent accurate assessment of total binding protein content by ligand blotting.
81 1706566 The possibility that sodium dodecyl sulfate (SDS)-stable complexes of insulin-like growth factor I (IGF-I) and its binding proteins (IGF-BP) exist in rat serum has been examined by using SDS-polyacrylamide gel electrophoresis (PAGE) followed by both [125I]IGF-I ligand blotting and immunoblotting with antisera directed against either IGF-BP3 or IGF-I.
82 1706566 While ligand blotting of rat serum only revealed free IGF-BP subunits (Mr approximately 50, 35, and 30 kDa), immunoblotting with either the IGF-BP3 antiserum or IGF-I antiserum revealed major immunoreactive bands with higher molecular weights (greater than 110, approximately 100, and approximately 84 kDa).
83 1707131 Cloning of the rat insulin-like growth factor-binding protein-2 gene and identification of a functional promoter lacking a TATA box.
84 1707131 We have isolated clones encoding the rat insulin-like growth factor-binding protein-2 (IGFBP-2) gene and determined its organization and nucleotide sequence.
85 1707131 The amino acid sequences of exons 1, 3, and 4 are 32-50% identical to the corresponding exons of human IGFBP-1 and IGFBP-3, and 87-91% identical to those of human IGFBP-2.
86 1707131 It is GC rich (66% between nt -270 and +385) and contains GC boxes that might be recognized by transcription factors Sp1 or ETF.
87 1707131 The 5' flanking region also contains motifs that might be recognized by transcription factors AP-1 (Jun/Fos), AP-2, and liver factor B1.
88 1707131 Cloning of the rat insulin-like growth factor-binding protein-2 gene and identification of a functional promoter lacking a TATA box.
89 1707131 We have isolated clones encoding the rat insulin-like growth factor-binding protein-2 (IGFBP-2) gene and determined its organization and nucleotide sequence.
90 1707131 The amino acid sequences of exons 1, 3, and 4 are 32-50% identical to the corresponding exons of human IGFBP-1 and IGFBP-3, and 87-91% identical to those of human IGFBP-2.
91 1707131 It is GC rich (66% between nt -270 and +385) and contains GC boxes that might be recognized by transcription factors Sp1 or ETF.
92 1707131 The 5' flanking region also contains motifs that might be recognized by transcription factors AP-1 (Jun/Fos), AP-2, and liver factor B1.
93 1710510 Ovarian intrabursal administration of insulin-like growth factor-binding protein inhibits follicle rupture in gonadotropin-treated immature female rats.
94 1710510 The effects of an insulin-like growth factor-binding protein (IGF-BP) on rat follicular function were examined by using the technique of ovarian intrabursal (IB) injection.
95 1710510 Ligand blotting experiments using [125I]-labeled insulin-like growth factor I revealed that granulosa cells obtained from both untreated and eCG-treated rats synthesized and secreted two IGF-BPs of Mr 35,000 and 30,000.
96 1710510 Ovarian intrabursal administration of insulin-like growth factor-binding protein inhibits follicle rupture in gonadotropin-treated immature female rats.
97 1710510 The effects of an insulin-like growth factor-binding protein (IGF-BP) on rat follicular function were examined by using the technique of ovarian intrabursal (IB) injection.
98 1710510 Ligand blotting experiments using [125I]-labeled insulin-like growth factor I revealed that granulosa cells obtained from both untreated and eCG-treated rats synthesized and secreted two IGF-BPs of Mr 35,000 and 30,000.
99 1713293 Differential expression of insulin-like growth factor-I and insulin-like growth factor binding protein-1 in the diabetic rat.
100 1713293 In this report we have examined the effects of streptozotocin-induced (STZ) diabetes on expression of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) in various tissues.
101 1713293 In contrast to the decrease in IGF-I mRNA, IGFBP-1 mRNA was significantly increased in the liver and kidney of diabetic rats.
102 1713293 In diabetic rats, a highly significant correlation (R = 0.75, p less than 0.001) between hepatic IGFBP-1 mRNA and glucose was observed whereas there was no significant correlation between serum glucose and hepatic IGF-I mRNA abundance (R = 0.24, p = NS).
103 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.
104 1713293 The observations reported here are consistent with the hypothesis that diminished IGF-I expression and inhibition of available IGF-I by increased levels of IGFBP-1 may explain the impaired growth seen in diabetic animals.
105 1713293 Differential expression of insulin-like growth factor-I and insulin-like growth factor binding protein-1 in the diabetic rat.
106 1713293 In this report we have examined the effects of streptozotocin-induced (STZ) diabetes on expression of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) in various tissues.
107 1713293 In contrast to the decrease in IGF-I mRNA, IGFBP-1 mRNA was significantly increased in the liver and kidney of diabetic rats.
108 1713293 In diabetic rats, a highly significant correlation (R = 0.75, p less than 0.001) between hepatic IGFBP-1 mRNA and glucose was observed whereas there was no significant correlation between serum glucose and hepatic IGF-I mRNA abundance (R = 0.24, p = NS).
109 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.
110 1713293 The observations reported here are consistent with the hypothesis that diminished IGF-I expression and inhibition of available IGF-I by increased levels of IGFBP-1 may explain the impaired growth seen in diabetic animals.
111 1719383 Isolation and molecular cloning of insulin-like growth factor-binding protein-6.
112 1719383 Insulin-like growth factors (IGFs) together with their binding proteins (BPs) are potential regulators of folliculogenesis in mammalian ovary.
113 1719386 Insulin rapidly inhibits insulin-like growth factor-binding protein-1 gene expression in H4-II-E rat hepatoma cells.
114 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.
115 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.
116 1719386 IGFBP-1 mRNA also is increased in the livers of diabetic rats and decreased by insulin treatment.
117 1719386 To understand the molecular basis for this regulation, we have examined the effects of insulin on IGFBP-1 and IGFBP-1 mRNA in the H4-II-E cell line derived from the well differentiated H35 rat hepatoma.
118 1719386 Incubation of H4-II-E cells with insulin for 24 h decreased IGFBP-1 in the culture medium by approximately 50%.
119 1719386 Inhibition was observed at physiological concentrations of insulin (ED50, less than 0.5 nM), but not at higher concentrations of IGF-II.
120 1719386 These results, together with the fact that H4-II-E cells do not possess IGF-I receptors with which insulin might cross-react, suggest that insulin acts via the insulin receptor.
121 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.
122 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.
123 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.
124 1719386 Thus, insulin, acting through the insulin receptor, rapidly decreases the abundance of IGFBP-1 mRNA in H4-II-E cells.
125 1719386 We propose that regulation of IGFBP-1 synthesis is an important component of the regulation of IGFBP-1 by insulin in vivo.
126 1722613 Hormonal regulation of insulin-like growth factor binding protein-1 expression in the rat.
127 2007436 The high- and low-incidence strains, established in the 20th generation, were named the ALS (alloxan-induced diabetes-susceptible) and ALR (alloxan-induced diabetes-resistant) strains, respectively.
128 2152877 Tissue, developmental, and metabolic regulation of messenger ribonucleic acid encoding a rat insulin-like growth factor-binding protein.
129 2152877 Insulin-like growth factor-II (IGF-II) is the predominant insulin-like growth factor in fetal and neonatal rat serum and tissues.
130 2164920 Production of the rat type 1 insulin-like growth factor-binding protein by well differentiated H4EIIC3 hepatoma cells: identification, purification, and N-terminal amino acid analysis.
131 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).
132 2164920 Purified protein bound both IGF-I and IGF-II with high affinity.
133 2448329 Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein.
134 2448329 The serum levels of 34K insulin-like growth factor (IGF)-binding protein were measured by RIA in 88 type 1 diabetic patients, 9 patients with type 2 diabetes, 7 patients with insulinoma, 19 normal subjects (all after an overnight fast), and 82 normal subjects after a breakfast meal.
135 2448329 In conclusion, 1) serum 34K IGF-binding protein levels are elevated in type 1 and 2 diabetic patients and decreased in patients with insulinoma; 2) the serum binding protein, but not IGF-I concentration is decreased by acute hyperinsulinemia; and 3) these data suggest that the serum insulin concentration plays a role in regulation of the serum 34K IGF-binding protein concentration.
136 2462572 Prolonged exercise increases serum insulin-like growth factor-binding protein concentrations.
137 2462572 We studied the response of serum 34K insulin-like growth factor-binding protein (IGF-BP) to two types of prolonged exercise.
138 2462572 After completion of the ski race, the serum insulin and IGF-BP levels (r = -0.70; P less than 0.05), and serum IGF-I and IGF-BP levels (r = -0.72; P less than 0.05) were inversely correlated in the normal men.
139 2462572 We conclude that 1) long term exercise increases serum IGF-BP concentrations in both normal and type 1 diabetic men; and 2) the increases are inversely related to alterations in serum IGF-I and insulin concentrations in normal men.
140 2462572 Prolonged exercise increases serum insulin-like growth factor-binding protein concentrations.
141 2462572 We studied the response of serum 34K insulin-like growth factor-binding protein (IGF-BP) to two types of prolonged exercise.
142 2462572 After completion of the ski race, the serum insulin and IGF-BP levels (r = -0.70; P less than 0.05), and serum IGF-I and IGF-BP levels (r = -0.72; P less than 0.05) were inversely correlated in the normal men.
143 2462572 We conclude that 1) long term exercise increases serum IGF-BP concentrations in both normal and type 1 diabetic men; and 2) the increases are inversely related to alterations in serum IGF-I and insulin concentrations in normal men.
144 2468706 The serum levels of the low molecular form of insulin-like growth factor binding protein (IGFBP) was determined in 56 outpatients with diabetes mellitus by a radioimmunoassay developed for amniotic 35 kDa IGFBP.
145 2474047 Levels of the small insulin-like growth factor-binding protein are strongly related to those of insulin in prepubertal and pubertal children but only weakly so after puberty.
146 2474047 We have looked at the relationship between fasting levels of insulin and a small insulin-like growth factor (IGF)-binding protein (IBP-1) in a cross-sectional study of 116 normal subjects aged 5-48 years.
147 2474047 The relationship between IBP-1 and insulin was also examined within individual normal children in overnight profiles of IBP-1 and insulin obtained from two children at each stage of puberty (Tanner stages 1-5).
148 2474047 In the cross-sectional study high levels of IBP-1 were found in early childhood and these fell throughout puberty as fasting levels of insulin rose.
149 2474047 After the age of 16 IBP-1 levels remained low despite fasting insulin levels returning to prepubertal levels.
150 2474047 A strong negative correlation was obtained between IBP-1 and insulin in children of 5-16 years (r = -0.63; n = 60; P less than 0.001), no such relationship being found after the age of 16.
151 2474047 In the second study, IBP-1 underwent a marked circadian variation in all cases and an inverse correlation with insulin, measured at the same time, was obtained at pubertal stages 1 to 4, but not at stage 5 (pooled data stages 1-4, r = -0.69; n = 53; P less than 0.001).
152 2474129 Structure of the human chromosomal gene for the 25 kilodalton insulin-like growth factor binding protein.
153 2474129 We have characterized the structure of the human chromosomal gene for the 25 kilodalton insulin-like growth factor binding protein (BP-25) as a first step toward understanding both the factors which regulate BP-25 transcription and also the evolution of the insulin-like growth factor binding proteins.
154 2474129 Structure of the human chromosomal gene for the 25 kilodalton insulin-like growth factor binding protein.
155 2474129 We have characterized the structure of the human chromosomal gene for the 25 kilodalton insulin-like growth factor binding protein (BP-25) as a first step toward understanding both the factors which regulate BP-25 transcription and also the evolution of the insulin-like growth factor binding proteins.
156 2476266 Evidence is accumulating that a non-GH dependent insulin-like growth factor-binding protein (IGF-BP) is not only a carrier protein but also has an active role in the growth process.
157 2476984 Identification of a type 1 insulin-like growth factor binding protein (IGF BP) in serum from rats with diabetes mellitus.
158 2476984 Circulating insulin-like growth factor binding protein (IGF BP) activity is increased in animals with streptozotocin-induced diabetes.
159 2476984 This BP is immunologically distinct from the low molecular weight fetal rat BP (rBP2) and is related to the human amniotic fluid BP (hBP1) that is increased in patients with insulin dependent diabetes mellitus.
160 2476984 Identification of a type 1 insulin-like growth factor binding protein (IGF BP) in serum from rats with diabetes mellitus.
161 2476984 Circulating insulin-like growth factor binding protein (IGF BP) activity is increased in animals with streptozotocin-induced diabetes.
162 2476984 This BP is immunologically distinct from the low molecular weight fetal rat BP (rBP2) and is related to the human amniotic fluid BP (hBP1) that is increased in patients with insulin dependent diabetes mellitus.
163 2480035 [Placental protein 12 (PP 12)/insulin-like growth factor binding protein (IGF-bp) in pregnancy in metabolically healthy patients and diabetic patients with retinopathy].
164 2480035 The placental protein 12 (PP 12) was found to be identical with the insulin like growth-factor binding protein (IGF-bp).
165 2480035 [Placental protein 12 (PP 12)/insulin-like growth factor binding protein (IGF-bp) in pregnancy in metabolically healthy patients and diabetic patients with retinopathy].
166 2480035 The placental protein 12 (PP 12) was found to be identical with the insulin like growth-factor binding protein (IGF-bp).
167 2480787 Complementary DNA structure of the high molecular weight rat insulin-like growth factor binding protein (IGF-BP3) and tissue distribution of its mRNA.
168 2480787 Insulin-like growth factors (IGFs) found in extracellular fluids are bound to specific binding proteins.
169 2480787 Recently a high molecular weight IGF-binding protein (IGF-BP3) has been isolated from porcine ovarian follicular fluid based on its inhibition of follicle stimulating hormone-stimulated estradiol production in rat granulosa cells.
170 2481706 Insulin and variation in glucose levels modify the secretion rates of the growth hormone-independent insulin-like growth factor binding protein-1 in the human hepatoblastoma cell line Hep G2.
171 2481706 The plasma level of the GH-independent insulin-like growth factor binding-protein-1 (IGFBP-1) is regulated inversely by insulin.
172 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.
173 2481706 Insulin suppressed IGFBP-1 secretion maximally at 100 mU/l (-32%) within 6 h.
174 2481706 Stimulation by varying glucose levels and suppression by insulin of IGFBP-1 secretion persisted on return to control conditions after the removal of physiological concentrations of glucose (4-12 mmol/l) and insulin (50-500 mU/l).
175 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.
176 2481706 Insulin and variation in glucose levels modify the secretion rates of the growth hormone-independent insulin-like growth factor binding protein-1 in the human hepatoblastoma cell line Hep G2.
177 2481706 The plasma level of the GH-independent insulin-like growth factor binding-protein-1 (IGFBP-1) is regulated inversely by insulin.
178 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.
179 2481706 Insulin suppressed IGFBP-1 secretion maximally at 100 mU/l (-32%) within 6 h.
180 2481706 Stimulation by varying glucose levels and suppression by insulin of IGFBP-1 secretion persisted on return to control conditions after the removal of physiological concentrations of glucose (4-12 mmol/l) and insulin (50-500 mU/l).
181 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.
182 7490544 Effects of maternal diabetes on fetal expression of insulin-like growth factor and insulin-like growth factor binding protein mRNAs in the rat.
183 7490544 Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs).
184 7490544 In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes.
185 7505461 Developmental regulation of insulin-like growth factor binding protein-2 in chick embryo serum and vitreous humor.
186 7505461 Insulin-like growth factor I (IGF-I), a potent mitogen, is thought to contribute to the general growth of the embryo as an endocrine factor, and as a paracrine factor to the development of the early embryo and of specific organs such as the eye.
187 7505461 Like serum IGFBP-2, levels of immunoreactive IGF-I in serum are higher in the second week of embryogenesis than the first.
188 7505461 Despite this correlation, changes in IGFBP-2 do not appear to be regulated by IGF-I: (a) serum IGF-I decreases after day 15, whereas IGFBP-2 levels remain stable until hatching; (b) vitreous IGF-I, like serum IGF-I, is higher in the second week of embryogenesis, whereas vitreous IGFBP-2 is highest in the first week; (c) embryos cultured ex ovo express IGFBP-2 at E15-E19, although they lack the normal mid-embryogenesis surge in IGF-I.
189 7505461 We conclude that vitreous IGFBP-2 is synthesized locally in the eye, and that the expression of IGFBP-2 in chick embryos is not directly regulated by IGF-I.
190 7505735 Intraperitoneal insulin affects insulin-like growth factor binding protein-1 in a well-controlled type I diabetic patient.
191 7506819 To address the possibility that patients with CFDM might have suppressed pituitary growth hormone (GH) release as a result of increased plasma somatostatin, GH secretion in 8 CFDM patients and 8 normal male controls was studied using a standard arginine infusion stimulus.
192 7506819 Concentrations of the GH-dependent peptides, insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) were also measured.
193 7506819 Despite higher GH levels in the CFDM patients, their IGF-I and IGFBP-3 concentrations were low.
194 7507068 Regulation of insulin-like growth factor-binding protein-1 in rat serum.
195 7507068 Previous studies support a role for insulin-like growth factor-binding protein-1 (IGFBP-1) in modulating insulin-like growth factor (IGF) availability for glucose homeostasis.
196 7507068 IGFBP-1 concentrations were suppressed by > 50% in two rat models of insulin resistance.
197 7507068 Regulation of insulin-like growth factor-binding protein-1 in rat serum.
198 7507068 Previous studies support a role for insulin-like growth factor-binding protein-1 (IGFBP-1) in modulating insulin-like growth factor (IGF) availability for glucose homeostasis.
199 7507068 IGFBP-1 concentrations were suppressed by > 50% in two rat models of insulin resistance.
200 7509650 [The content of the PAMG-1 protein that binds insulin-like growth factor I (somatomedin C) in the blood serum of diabetic patients].
201 7509650 The study was undertaken to measure PAMG-1 (PP 12, IGEBP-1) that is insulin-like growth factor binding protein in blood sera of diabetic patients.
202 7509771 Insulin-like growth factor-binding protein-1s are important modulators of the insulin-like growth factors that may have both positive and negative effects on the ability of insulin-like growth factors to stimulate cell growth.
203 7512318 Serum insulin-like growth factor binding protein-1 in pregnant women: decreased concentrations following an oral glucose load.
204 7512318 Serum concentrations of insulin-like growth factor binding protein-1 (IGFBP-1) were measured in men and in non-pregnant and pregnant women.
205 7512318 Following administration of an oral glucose load, serum IGFBP-1 concentrations were decreased within 2 h in men and in pregnant women while IGF-I levels remained constant.
206 7512318 These results suggested that IGFBP-1 regulates IGF-I activity in pregnancy in a similar manner to that in the non-pregnant state.
207 7512318 Serum insulin-like growth factor binding protein-1 in pregnant women: decreased concentrations following an oral glucose load.
208 7512318 Serum concentrations of insulin-like growth factor binding protein-1 (IGFBP-1) were measured in men and in non-pregnant and pregnant women.
209 7512318 Following administration of an oral glucose load, serum IGFBP-1 concentrations were decreased within 2 h in men and in pregnant women while IGF-I levels remained constant.
210 7512318 These results suggested that IGFBP-1 regulates IGF-I activity in pregnancy in a similar manner to that in the non-pregnant state.
211 7512496 Coculture of primary rat hepatocytes and nonparenchymal cells permits expression of insulin-like growth factor binding protein-3 in vitro.
212 7512496 In biological fluids, the insulin-like growth factors (IGFs) are associated with binding proteins (IGFBPs), which modify IGF distribution and action.
213 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.
214 7512496 Our findings suggest that GH may act indirectly to promote IGFBP-3 generation in vivo via increasing both the secretion of insulin and the hepatic production of IGF-I; in patients with diabetes mellitus, reduced circulating levels of IGFBP-3 despite high levels of GH may result from both insulin deficiency and inadequate hepatic production of IGF-I.
215 7513716 Increased proteolysis of insulin-like growth factor-binding protein-3 (IGFBP-3) in noninsulin-dependent diabetes mellitus serum, with elevation of a 29-kilodalton (kDa) glycosylated IGFBP-3 fragment contained in the approximately 130- to 150-kDa ternary complex.
216 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.
217 7513716 Proteolysis of IGFBP-3 may alter the distribution of IGF-I between these complexes by reducing IGFBP-3 affinity for IGF-I and/or acid-labile subunit and may offer an additional mechanism for regulation of IGF availability.
218 7513716 Further studies are required to determine whether the avidity of ternary complex formation with the 29-kDa IGFBP-3 fragment is reduced and whether the resulting increased IGF turnover can explain the reduced IGF-I levels (z scores) observed in NIDDM patients compared to healthy subjects (-0.81 +/- 0.32 SD vs. +0.26 +/- 0.17 SD; P < 0.001).
219 7514206 Insulin-like growth factor-binding protein-1 is correlated with low density lipoprotein cholesterol in normal subjects.
220 7514206 Insulin-like growth factor-I (IGF-I) has been inversely associated with low-density lipoprotein (LDL) cholesterol in normal women with slightly elevated cholesterol levels and hypothyroid women.
221 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.
222 7514206 Elevated IGFBP-1 levels have been associated with an inhibition of serum IGF-I bioactivity in children with insulin-dependent diabetes.
223 7514206 IGFBP-1 also appears to inhibit IGF-I hexose-stimulated uptake.
224 7514335 Insulin-like growth factor binding protein-1: identification, purification, and regulation in fetal and adult life.
225 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.
226 7514335 Glucocorticoids exert important effects on circulating levels and hepatic expression of IGFBP-1 in vivo under conditions where insulin levels are low.
227 7514335 Regulation of hepatic production of IGFBP-1 may provide a mechanism by which insulin and counter-regulatory factors may modulate the availability of IGFs and the biological effects of IGFs in both fetal and adult life.
228 7514336 Rapid regulation of insulin-like growth factor binding protein-1 transcription by insulin in vivo and in vitro.
229 7515391 Phosphorylation of insulin-like growth factor binding protein-1 in patients with insulin-dependent diabetes mellitus and severe trauma.
230 7515391 We have determined the level of phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) in serum during two catabolic states: diabetes mellitus and trauma.
231 7515391 Human sera were incubated with [125I]IGF-I for 2 h followed by non-denaturing PAGE. [125I]IGF-I/IGFBP-1 complexes from serum co-migrated with a pure p4IGFBP-1 standard.
232 7515391 The migration of IGF-I/pIGFBP-1 complexes was retarded by IGFBP-1 antibodies, but not by antibodies against IGFBP-2 or IGFBP-3.
233 7515391 Phosphorylation of insulin-like growth factor binding protein-1 in patients with insulin-dependent diabetes mellitus and severe trauma.
234 7515391 We have determined the level of phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) in serum during two catabolic states: diabetes mellitus and trauma.
235 7515391 Human sera were incubated with [125I]IGF-I for 2 h followed by non-denaturing PAGE. [125I]IGF-I/IGFBP-1 complexes from serum co-migrated with a pure p4IGFBP-1 standard.
236 7515391 The migration of IGF-I/pIGFBP-1 complexes was retarded by IGFBP-1 antibodies, but not by antibodies against IGFBP-2 or IGFBP-3.
237 7521339 Glucagon stimulates insulin-like growth factor binding protein-1 secretion in healthy subjects, patients with pituitary insufficiency, and patients with insulin-dependent diabetes mellitus.
238 7521339 Glucagon (1-1.5 mg) was administrated iv as a bolus dose to healthy individuals (n = 7), patients with GH deficiency (n = 14), and patients with insulin-dependent diabetes mellitus (IDDM; n = 6).
239 7521339 Thereafter, blood samples for determination of serum glucose, insulin, insulin-like growth factor-binding protein-1 (IGFBP-1), GH, and insulin-like growth factor-I (IGF-I) concentrations were collected for 180 min.
240 7521339 IGFBP-1 concentrations increased significantly in response to glucagon, with maximal values observed at 90 min [in healthy subjects from 36 +/- 6 to 58 +/- 10 micrograms/L (P < 0.05), in GH-deficient patients from 36 +/- 4 to 54 +/- 6 micrograms/L (P < 0.001), and in IDDM patients from 115 +/- 18 to 167 +/- 27 micrograms/L (P < 0.05)].
241 7521339 The IGFBP-1 elevation was delayed in relation to the glucagon-induced increase in glucose and insulin concentrations.
242 7521339 When the groups were combined, the individual IGFBP-1 peak value observed at 90 min was inversely correlated to the individual peak value of insulin observed at 15-30 min (r = -0.743; P < 0.001).
243 7521339 In healthy subjects and IDDM patients, mean GH levels did not change significantly, whereas mean IGF-I concentrations decreased slightly at 30 min.
244 7521339 Glucagon stimulates insulin-like growth factor binding protein-1 secretion in healthy subjects, patients with pituitary insufficiency, and patients with insulin-dependent diabetes mellitus.
245 7521339 Glucagon (1-1.5 mg) was administrated iv as a bolus dose to healthy individuals (n = 7), patients with GH deficiency (n = 14), and patients with insulin-dependent diabetes mellitus (IDDM; n = 6).
246 7521339 Thereafter, blood samples for determination of serum glucose, insulin, insulin-like growth factor-binding protein-1 (IGFBP-1), GH, and insulin-like growth factor-I (IGF-I) concentrations were collected for 180 min.
247 7521339 IGFBP-1 concentrations increased significantly in response to glucagon, with maximal values observed at 90 min [in healthy subjects from 36 +/- 6 to 58 +/- 10 micrograms/L (P < 0.05), in GH-deficient patients from 36 +/- 4 to 54 +/- 6 micrograms/L (P < 0.001), and in IDDM patients from 115 +/- 18 to 167 +/- 27 micrograms/L (P < 0.05)].
248 7521339 The IGFBP-1 elevation was delayed in relation to the glucagon-induced increase in glucose and insulin concentrations.
249 7521339 When the groups were combined, the individual IGFBP-1 peak value observed at 90 min was inversely correlated to the individual peak value of insulin observed at 15-30 min (r = -0.743; P < 0.001).
250 7521339 In healthy subjects and IDDM patients, mean GH levels did not change significantly, whereas mean IGF-I concentrations decreased slightly at 30 min.
251 7521354 Effect of insulin on the hepatic production of insulin-like growth factor-binding protein-1 (IGFBP-1), IGFBP-3, and IGF-I in insulin-dependent diabetes.
252 7521354 Insulin-like growth factors (IGFs) circulate attached to binding proteins (IGFBPs).
253 7521354 The main source of circulating IGF-I and IGFBP-1 is considered to be the liver, but that of circulating IGFBP-3 is not known.
254 7521354 IGF-I and IGFBP-3 are GH dependent, whereas IGFBP-1 is insulin regulated.
255 7521354 The aim of the present study was to examine the effect of insulin on the hepatic secretion of IGFBP-1, IGFBP-3, and IGF-I.
256 7521354 Fasting IGFBP-1 concentrations were inversely correlated to the insulin levels (r = -0.918; P < 0.001).
257 7521354 There was a significant correlation in the hepatic vein between fasting IGF-I and IGFBP-3 levels (r = 0.928; P < 0.001).
258 7521354 Basal splanchnic IGFBP-1 production was 18 +/- 7 micrograms/min, whereas no basal net exchanges of IGF-I or IGFBP-3 were observed across the splanchnic area.
259 7521354 Insulin inhibited splanchnic IGFBP-1 production within 120 min and glucose output within 20 min.
260 7521354 Serum IGF-I, but not IGFBP-3, concentrations increased significantly during the insulin infusion.
261 7521354 In summary, this study demonstrates the existence of considerable IGFBP-1 production from the liver during insulinopenia and the complete blocking of splanchnic IGFBP-1 production and increases in serum levels of IGF-I by insulin despite no effect on IGFBP-3 levels.
262 7521354 Thus, insulin may play a role in determining the bioavailability of IGF-I.
263 7523002 Insulin-like growth factor binding protein 1 response to acute insulin induced hypoglycaemia in type 1 diabetes.
264 7523864 Identification of cis-elements mediating the stimulation of rat insulin-like growth factor-binding protein-1 promoter activity by dexamethasone, cyclic adenosine 3',5'-monophosphate, and phorbol esters, and inhibition by insulin.
265 7523864 Insulin-like growth factor-binding protein-1 (IGFBP-1) modulates the action of IGFs on target cells.
266 7523864 This insulin response element is conserved in the human IGFBP-1 promoter and is homologous to the insulin response element of the phosphoenolpyruvate carboxykinase gene, which also is rapidly inhibited by insulin in H4-II-E cells.
267 7523864 Identification of cis-elements mediating the stimulation of rat insulin-like growth factor-binding protein-1 promoter activity by dexamethasone, cyclic adenosine 3',5'-monophosphate, and phorbol esters, and inhibition by insulin.
268 7523864 Insulin-like growth factor-binding protein-1 (IGFBP-1) modulates the action of IGFs on target cells.
269 7523864 This insulin response element is conserved in the human IGFBP-1 promoter and is homologous to the insulin response element of the phosphoenolpyruvate carboxykinase gene, which also is rapidly inhibited by insulin in H4-II-E cells.
270 7524886 Insulin-like growth factor-I (IGF-I) has been proposed to be important in the endocrine control of fetal growth in humans, although serum IGF-I concentrations are 10-fold lower than during rapid pubertal growth.
271 7524886 We have recently suggested that the bioavailability of circulating IGF-I is increased in the human fetus due to the molar excess of IGF-I plus IGF-II relative to IGFBP-3 as well as the increased concentrations of IGFBP-2, which does not form a long-lived ternary complex.
272 7524886 We have presently studied ternary complex formation between IGF, IGFBP-3, and acid labile subunit (ALS) to further assess if IGF-I bioavailability is increased in human fetal serum.
273 7524886 Despite the predominance of the 29 kDa IGFBP-3 fragment, we have previously demonstrated that the IGFBP-3 protease activity is not increased in fetal serum, in contrast to pregnancy or non-insulin dependent diabetes mellitus (NIDDM) sera.
274 7525123 Inverse correlation between insulin-like growth factor binding protein-1 and insulin in patients with acromegaly during treatment with the somatostatin analogue octreotide.
275 7525263 Recombinant human insulin-like growth factor (IGF)-binding protein-6 inhibits IGF-II-induced differentiation of L6A1 myoblasts.
276 7525263 Insulin-like growth factor-binding protein-6 (IGFBP-6) is an O-linked glycoprotein that binds insulin-like growth factor-II (IGF-II) with marked preferential affinity over IGF-I.
277 7525263 The effect of rhIGFBP-6 on IGF-induced L6A1 myoblast differentiation was studied using creatine kinase activity as an index of differentiation. rhIGFBP-6 inhibited differentiation initiated by IGF-II in a dose-dependent manner, inhibition was complete when rhIGFBP-6 was present in a slight molar excess.
278 7525263 These results are consistent with the preferential affinity of IGFBP-6 for IGF-II.
279 7527331 Regulation in vivo of the acid-labile subunit of the rat serum insulin-like growth factor-binding protein complex.
280 7527331 The acid-labile subunit (ALS) and insulin-like growth factor (IGF)-binding protein-3 are glycoproteins that form a complex carrying about 90% of the circulating IGFs.
281 7527331 Fasting for 24 or 48 h decreased serum IGF-I and ALS levels, but not hepatic ALS mRNA.
282 7527331 Insulin treatment normalized serum ALS without fully restoring ALS mRNA.
283 7527331 Regulation in vivo of the acid-labile subunit of the rat serum insulin-like growth factor-binding protein complex.
284 7527331 The acid-labile subunit (ALS) and insulin-like growth factor (IGF)-binding protein-3 are glycoproteins that form a complex carrying about 90% of the circulating IGFs.
285 7527331 Fasting for 24 or 48 h decreased serum IGF-I and ALS levels, but not hepatic ALS mRNA.
286 7527331 Insulin treatment normalized serum ALS without fully restoring ALS mRNA.
287 7527331 Regulation in vivo of the acid-labile subunit of the rat serum insulin-like growth factor-binding protein complex.
288 7527331 The acid-labile subunit (ALS) and insulin-like growth factor (IGF)-binding protein-3 are glycoproteins that form a complex carrying about 90% of the circulating IGFs.
289 7527331 Fasting for 24 or 48 h decreased serum IGF-I and ALS levels, but not hepatic ALS mRNA.
290 7527331 Insulin treatment normalized serum ALS without fully restoring ALS mRNA.
291 7527331 Regulation in vivo of the acid-labile subunit of the rat serum insulin-like growth factor-binding protein complex.
292 7527331 The acid-labile subunit (ALS) and insulin-like growth factor (IGF)-binding protein-3 are glycoproteins that form a complex carrying about 90% of the circulating IGFs.
293 7527331 Fasting for 24 or 48 h decreased serum IGF-I and ALS levels, but not hepatic ALS mRNA.
294 7527331 Insulin treatment normalized serum ALS without fully restoring ALS mRNA.
295 7530285 Differential regulation of insulin-like growth factor binding protein-2 and -4 mRNA in muscle tissues and liver by diabetes or fasting.
296 7530285 The present study was undertaken to investigate the metabolic regulation of insulin-like growth factor binding proteins (IGFBPs) gene expression in muscles from diabetic or fasted rat.
297 7530285 The messenger RNA (mRNA) levels for IGFBP-2 and -4 were analysed by solution hybridization in heart, skeletal and smooth muscle and liver from fasted (3 days) and refed (6, 12, 24, 72 h) rats and rats made diabetic with streptozotocin.
298 7530285 In aortic intima-media, the mRNA levels for IGFBP-2 and -4 were decreased by diabetes or fasting and were restored gradually by refeeding.
299 7530285 The response of IGFBP-4 mRNA to diabetes appeared two days after injection of streptozotocin, while a significant decrease of IGFBP-2 mRNA was found after a diabetes duration of two weeks.
300 7530285 In contrast, liver IGFBP-2 mRNA was much lower in amount than IGF-I mRNA and IGFBP-4 mRNA and was sharply elevated by fasting, and decreased by refeeding.
301 7530285 In conclusion, 1) both IGFBP-2 and -4 mRNA in various tissues are regulated by diabetes or fasting; 2) the mRNA for IGFBP-2 is metabolically regulated in a discordant, organ-specific manner.
302 7530649 A major portion of the 150-kilodalton insulin-like growth factor-binding protein (IGFBP) complex in adult rat serum contains unoccupied, proteolytically nicked IGFBP-3 that binds IGF-II preferentially.
303 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.
304 7530649 A 150-kDa pool, isolated after neutral Sephadex G-200 gel filtration of adult rat serum, bound IGF-II with approximately 80-fold greater affinity than IGF-I, but did not contain immunoprecipitable IGF-II/mannose-6-phosphate receptors, which bind IGF-II with the same preferential affinity.
305 7530649 Exogenous IGF-II bound to the 150-kDa complex without displacing endogenous IGF-I, indicating that it bound to sites that were previously unoccupied.
306 7530649 In competitive binding assays, IGF-binding proteins (IGFBPs) in the acid eluate bound IGF-II with higher affinity than IGF-I, whereas IGFBPs in the flow-through, after acid stripping, bound IGF-I and IGF-II with similar affinity.
307 7530649 The acid eluate and the acid-stripped flow-through predominantly formed 50-kDa complexes with [125I]IGF-II when affinity-cross-linked and examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; these complexes were precipitated by antibodies to rat IGFBP-3.
308 7530649 Larger complexes (> 95 kDa) present in the nonacidified 150-kDa pool were not observed, consistent with the IGFBP-3 molecules in the flow-through and eluate having been complexed to an acid-labile subunit (ALS).
309 7530649 We conclude that the 150-kDa fraction of adult rat serum includes 1) ternary complexes of intact IGFBP-3 (which binds IGF-I and IGF-II with similar affinity), endogenous IGF-I, and the ALS; and 2) binary complexes of proteolytically nicked IGFBP-3 and ALS that bind IGF-II preferentially.
310 7530649 A major portion of the 150-kilodalton insulin-like growth factor-binding protein (IGFBP) complex in adult rat serum contains unoccupied, proteolytically nicked IGFBP-3 that binds IGF-II preferentially.
311 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.
312 7530649 A 150-kDa pool, isolated after neutral Sephadex G-200 gel filtration of adult rat serum, bound IGF-II with approximately 80-fold greater affinity than IGF-I, but did not contain immunoprecipitable IGF-II/mannose-6-phosphate receptors, which bind IGF-II with the same preferential affinity.
313 7530649 Exogenous IGF-II bound to the 150-kDa complex without displacing endogenous IGF-I, indicating that it bound to sites that were previously unoccupied.
314 7530649 In competitive binding assays, IGF-binding proteins (IGFBPs) in the acid eluate bound IGF-II with higher affinity than IGF-I, whereas IGFBPs in the flow-through, after acid stripping, bound IGF-I and IGF-II with similar affinity.
315 7530649 The acid eluate and the acid-stripped flow-through predominantly formed 50-kDa complexes with [125I]IGF-II when affinity-cross-linked and examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; these complexes were precipitated by antibodies to rat IGFBP-3.
316 7530649 Larger complexes (> 95 kDa) present in the nonacidified 150-kDa pool were not observed, consistent with the IGFBP-3 molecules in the flow-through and eluate having been complexed to an acid-labile subunit (ALS).
317 7530649 We conclude that the 150-kDa fraction of adult rat serum includes 1) ternary complexes of intact IGFBP-3 (which binds IGF-I and IGF-II with similar affinity), endogenous IGF-I, and the ALS; and 2) binary complexes of proteolytically nicked IGFBP-3 and ALS that bind IGF-II preferentially.
318 7530649 A major portion of the 150-kilodalton insulin-like growth factor-binding protein (IGFBP) complex in adult rat serum contains unoccupied, proteolytically nicked IGFBP-3 that binds IGF-II preferentially.
319 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.
320 7530649 A 150-kDa pool, isolated after neutral Sephadex G-200 gel filtration of adult rat serum, bound IGF-II with approximately 80-fold greater affinity than IGF-I, but did not contain immunoprecipitable IGF-II/mannose-6-phosphate receptors, which bind IGF-II with the same preferential affinity.
321 7530649 Exogenous IGF-II bound to the 150-kDa complex without displacing endogenous IGF-I, indicating that it bound to sites that were previously unoccupied.
322 7530649 In competitive binding assays, IGF-binding proteins (IGFBPs) in the acid eluate bound IGF-II with higher affinity than IGF-I, whereas IGFBPs in the flow-through, after acid stripping, bound IGF-I and IGF-II with similar affinity.
323 7530649 The acid eluate and the acid-stripped flow-through predominantly formed 50-kDa complexes with [125I]IGF-II when affinity-cross-linked and examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; these complexes were precipitated by antibodies to rat IGFBP-3.
324 7530649 Larger complexes (> 95 kDa) present in the nonacidified 150-kDa pool were not observed, consistent with the IGFBP-3 molecules in the flow-through and eluate having been complexed to an acid-labile subunit (ALS).
325 7530649 We conclude that the 150-kDa fraction of adult rat serum includes 1) ternary complexes of intact IGFBP-3 (which binds IGF-I and IGF-II with similar affinity), endogenous IGF-I, and the ALS; and 2) binary complexes of proteolytically nicked IGFBP-3 and ALS that bind IGF-II preferentially.
326 7534144 Regulation of insulin-like growth factor binding protein-1 (IGFBP-1) in insulin-dependent diabetes mellitus.
327 7534144 The aim of the present study was to characterize the effect of 44 h of hyperglycaemia on diurnal levels of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-1 (IGF-1), growth hormone (GH) and glucagon in 7 well-controlled subjects with insulin-dependent diabetes mellitus (IDDM).
328 7534144 However, the IGFBP-1 levels were increased in these IDDM subjects despite a peripheral hyperinsulinemia.
329 7534144 An inverse correlation was found between IGFBP-1 and peripheral insulin levels both during periods of rapid changes in IGFBP-1 and insulin concentrations (i.e. morning hours) as well as during the total 24-h sampling period.
330 7534144 Total IGF-1 levels were low, but no further decrease was seen after 24 h of hyperglycaemia in the presence of unchanged insulin levels.
331 7534144 In conclusion, the present study clearly shows that the increased IGFBP-1 level seen during poor metabolic control in IDDM is not caused by hyperglycaemia.
332 7534144 Glucose levels per se do not influence either total IGF-1 or IGFBP-1 concentrations in well-insulinised diabetic patients.
333 7534144 Regulation of insulin-like growth factor binding protein-1 (IGFBP-1) in insulin-dependent diabetes mellitus.
334 7534144 The aim of the present study was to characterize the effect of 44 h of hyperglycaemia on diurnal levels of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-1 (IGF-1), growth hormone (GH) and glucagon in 7 well-controlled subjects with insulin-dependent diabetes mellitus (IDDM).
335 7534144 However, the IGFBP-1 levels were increased in these IDDM subjects despite a peripheral hyperinsulinemia.
336 7534144 An inverse correlation was found between IGFBP-1 and peripheral insulin levels both during periods of rapid changes in IGFBP-1 and insulin concentrations (i.e. morning hours) as well as during the total 24-h sampling period.
337 7534144 Total IGF-1 levels were low, but no further decrease was seen after 24 h of hyperglycaemia in the presence of unchanged insulin levels.
338 7534144 In conclusion, the present study clearly shows that the increased IGFBP-1 level seen during poor metabolic control in IDDM is not caused by hyperglycaemia.
339 7534144 Glucose levels per se do not influence either total IGF-1 or IGFBP-1 concentrations in well-insulinised diabetic patients.
340 7536208 Choice of treatment affects plasma levels of insulin-like growth factor-binding protein-1 in noninsulin-dependent diabetes mellitus.
341 7536208 Insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) modulates the metabolic and mitogenic effects of IGFs.
342 7536208 Although IGFBP-1 levels are abnormally high in insulin-dependent diabetes (IDDM), relatively little is known in NIDDM; conflicting data have suggested both high and low levels.
343 7536208 In sulfonylurea-treated patients there were markedly reduced plasma IGFBP-1 concentrations (median, interquartile range in parentheses): control, 61.0 (36-96) micrograms/L; sulfonylureas alone, 31.5 (21-61) micrograms/L (P < 0.01); and sulfonylureas plus insulin, 31.5 (9-53) micrograms/L (P < 0.01).
344 7536208 Once daily insulin was associated with values similar to those in the control group [62.0 (27-103) micrograms/L; P = NS], whereas IGFBP-1 levels were higher with multiple insulin injection therapy [156.0 (71-184) micrograms/L; P < 0.05].
345 7536208 Proinsulin levels were higher in sulfonylurea-treated patients, but there was no significant correlation between IGFBP-1 and proinsulin within any individual group.
346 7537614 Pre- and post-translational regulation of renal insulin-like growth factor binding protein-1 in insulin-deficient diabetes.
347 7539353 Identification and partial characterization of a proteinase specific for insulin-like growth factor binding protein-3 in aqueous and vitreous humors.
348 7543079 Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer.
349 7543079 Insulin-like growth factor I (IGF-I) is a potent mitogen for human breast-cancer cells in vitro.
350 7543079 In circulation, most of IGF-I is bound to IGF-binding protein 3 (IGFBP-3).
351 7543079 To assess the availability of IGF-I for receptor binding, we determined serum levels of IGF-I and IGFBP-3 and IGF-I/IGFBP-3 ratios.
352 7543079 Premenopausal cases showed elevated IGF-I serum concentrations, decreased IGFBP-3 levels and increased IGF-I/IGFBP-3 ratios.
353 7543079 The IGF-I/IGFBP-3 ratio was a significant breast-cancer risk factor, also after adjustment for age, family history, height, body-mass index, body-fat distribution, and serum levels of C-peptide.
354 7543079 The relative risk was 7.34 for the highest compared with the lowest quintile of IGF-I/IGFBP-3.
355 7543110 Insulin-like growth factor binding protein-3 proteolysis in children with insulin-dependent diabetes mellitus: a possible role for insulin in the regulation of IGFBP-3 protease activity.
356 7543110 Limited proteolysis of serum insulin-like growth factor (IGF) binding protein (IGFBP)-3 has been described in various conditions and may increase the bioavailability of IGFs.
357 7543110 To characterize the relationship between insulin and IGFBP-3 protease activity, we have examined serum IGFBP-3 proteolysis in children with untreated insulin-dependent diabetes mellitus (IDDM) and have followed the effect of insulin therapy on serum IGFBP-3 proteolysis at 1 day, 1 week, and 1 month after the initiation of insulin therapy.
358 7543110 Ligand blot analysis of sera from untreated children with IDDM showed that intact IGFBP-3 was 50 +/- 9% of the age-matched control pool.
359 7543110 After the initiation of insulin treatment, IGFBP-3 did not change significantly at 1 day after treatment but increased dramatically at 1 week (90 +/- 13%) and 1 month after treatment (102 +/- 13%).
360 7543110 In contrast, when measured by immunoradiometric assay (which detects both intact and fragments of IGFBP-3), IGFBP-3 levels were 70% of the control pool before insulin therapy and did not increase significantly until 1 month after treatment.
361 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.
362 7543110 After insulin, intact IGFBP-3 increased and the 30-kDa fragment decreased to values comparable to those observed in controls.
363 7543110 IGFBP-3 proteolysis was increased before insulin therapy (160 +/- 9%) and decreased to 81 +/- 9% at 1 week and to 71 +/- 11% at 1 month after insulin treatment.
364 7543110 During insulin therapy, serum IGFBP-3 protease activity decreased gradually to 91 +/- 5% of control values at 1 month.
365 7543110 Molecular sizes of the IGFBP-3 proteolytic fragments (30 kDa, 24 kDa, and 19 kDa) and inhibition profile of IGFBP-3 protease were similar in IDDM and pregnancy sera, indicating that similar proteases (cation-dependent serine proteases) were active in both conditions.
366 7543110 These results suggest an important role of insulin in the regulation of IGFBP-3 protease activity.
367 7543110 Increased IGFBP-3 proteolysis in the sera of children with IDDM may serve to counteract the catabolic state induced by insulin deficiency.
368 7545620 Gonadotropin-releasing hormone overcomes follicle-stimulating hormone's inhibition of insulin-like growth factor-5 synthesis and promotion of its degradation in rat granulosa cells.
369 7545620 The effect of a gonadotropin-releasing hormone-agonist (GnRH-a) on the synthesis of insulin-like growth factor-binding protein-5 (IGFBP-5), a physiological marker for atresia, was investigated.
370 7545620 In contrast, increasing doses of porcine follicle-stimulating hormone (pFSH) caused a biphasic effect on IGFBP-5 accumulation.
371 7545695 Altered relation between circulating levels of insulin-like growth factor-binding protein-1 and insulin in growth hormone-deficient patients and insulin-dependent diabetic patients compared to that in healthy subjects.
372 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).
373 7545695 As in healthy subjects, serum IGFBP-1 displayed a diurnal variation in GH-deficient as well as in IDDM patients, with lowest levels in the afternoon and evening and a rise with maximum levels during the night and morning.
374 7545695 Fasting and 24-h mean levels of IGFBP-1 were significantly higher in GH-deficient patients [61 +/- 12 (P < 0.01) and 39 +/- 6 micrograms/L (P < 0.01), respectively] and IDDM patients [72 +/- 18 (P < 0.01) and 45 +/- 9 micrograms/L (P < 0.01), respectively] compared to those in healthy subjects (27 +/- 4 and 18 +/- 2 micrograms/L, respectively).
375 7545695 An inverse relationship was found between IGFBP-1 and insulin in GH-deficient patients, both between 24-h mean values (r = -0.756; P < 0.001) and between fasting values (r = -0.721; P < 0.001).
376 7545695 Moreover, in GH-deficient patients, the diurnal mean levels of IGFBP-1 were inversely correlated to IGF-I (r = -0.477; P < 0.05) and body mass index (r = -0.450; P < 0.05).
377 7545695 When insulin was taken into account, a tendency for a negative correlation between IGFBP-1 and IGF-I (P = 0.054) remained, whereas the relationship to body mass index disappeared.
378 7545695 However, IGFBP-1 levels were elevated in relation to insulin levels in GH-deficient patients compared to healthy subjects (F = 48.7; P < 0.001 and F = 32.5; P < 0.001, diurnal mean values and fasting values, respectively).
379 7545695 Altered relation between circulating levels of insulin-like growth factor-binding protein-1 and insulin in growth hormone-deficient patients and insulin-dependent diabetic patients compared to that in healthy subjects.
380 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).
381 7545695 As in healthy subjects, serum IGFBP-1 displayed a diurnal variation in GH-deficient as well as in IDDM patients, with lowest levels in the afternoon and evening and a rise with maximum levels during the night and morning.
382 7545695 Fasting and 24-h mean levels of IGFBP-1 were significantly higher in GH-deficient patients [61 +/- 12 (P < 0.01) and 39 +/- 6 micrograms/L (P < 0.01), respectively] and IDDM patients [72 +/- 18 (P < 0.01) and 45 +/- 9 micrograms/L (P < 0.01), respectively] compared to those in healthy subjects (27 +/- 4 and 18 +/- 2 micrograms/L, respectively).
383 7545695 An inverse relationship was found between IGFBP-1 and insulin in GH-deficient patients, both between 24-h mean values (r = -0.756; P < 0.001) and between fasting values (r = -0.721; P < 0.001).
384 7545695 Moreover, in GH-deficient patients, the diurnal mean levels of IGFBP-1 were inversely correlated to IGF-I (r = -0.477; P < 0.05) and body mass index (r = -0.450; P < 0.05).
385 7545695 When insulin was taken into account, a tendency for a negative correlation between IGFBP-1 and IGF-I (P = 0.054) remained, whereas the relationship to body mass index disappeared.
386 7545695 However, IGFBP-1 levels were elevated in relation to insulin levels in GH-deficient patients compared to healthy subjects (F = 48.7; P < 0.001 and F = 32.5; P < 0.001, diurnal mean values and fasting values, respectively).
387 7588232 Purified rat acid-labile subunit and recombinant human insulin-like growth factor (IGF)-binding protein-3 can form a 150-kilodalton binary complex in vitro in the absence of IGFs.
388 7588232 Insulin-like growth factors (IGFs) circulate in plasma mainly as part of a 150-kilodalton (kDa) complex with 40- to 45-kDa IGF-binding protein-3 (IGFBP-3) and an approximately 85-kDa acid-labile subunit (ALS) that does not bind IGFs directly.
389 7588232 Although it has been thought that IGFBP-3 must first bind IGF-I or IGF-II before it can complex with ALS to form the 150-kDa complex, we recently showed that unoccupied 150-kDa binary complexes of IGFBP-3 and ALS are abundant in adult rat serum.
390 7588232 We now demonstrate that IGFBP-3 and rat (r)ALS can form 150-kDa complexes in the absence of IGFs.
391 7588232 ALS was purified from rat serum by anion exchange chromatography and affinity chromatography on an IGF-I-Sepharose column to which human (h) IGFBP-3 had been noncovalently bound.
392 7588232 The preparation contained less than 0.1 ng IGF-I/microgram(s) purified ALS.
393 7588232 In this experiment IGFBP-3 binding was slightly increased by coincubation with IGF-I.
394 7588232 Purified rat acid-labile subunit and recombinant human insulin-like growth factor (IGF)-binding protein-3 can form a 150-kilodalton binary complex in vitro in the absence of IGFs.
395 7588232 Insulin-like growth factors (IGFs) circulate in plasma mainly as part of a 150-kilodalton (kDa) complex with 40- to 45-kDa IGF-binding protein-3 (IGFBP-3) and an approximately 85-kDa acid-labile subunit (ALS) that does not bind IGFs directly.
396 7588232 Although it has been thought that IGFBP-3 must first bind IGF-I or IGF-II before it can complex with ALS to form the 150-kDa complex, we recently showed that unoccupied 150-kDa binary complexes of IGFBP-3 and ALS are abundant in adult rat serum.
397 7588232 We now demonstrate that IGFBP-3 and rat (r)ALS can form 150-kDa complexes in the absence of IGFs.
398 7588232 ALS was purified from rat serum by anion exchange chromatography and affinity chromatography on an IGF-I-Sepharose column to which human (h) IGFBP-3 had been noncovalently bound.
399 7588232 The preparation contained less than 0.1 ng IGF-I/microgram(s) purified ALS.
400 7588232 In this experiment IGFBP-3 binding was slightly increased by coincubation with IGF-I.
401 7588232 Purified rat acid-labile subunit and recombinant human insulin-like growth factor (IGF)-binding protein-3 can form a 150-kilodalton binary complex in vitro in the absence of IGFs.
402 7588232 Insulin-like growth factors (IGFs) circulate in plasma mainly as part of a 150-kilodalton (kDa) complex with 40- to 45-kDa IGF-binding protein-3 (IGFBP-3) and an approximately 85-kDa acid-labile subunit (ALS) that does not bind IGFs directly.
403 7588232 Although it has been thought that IGFBP-3 must first bind IGF-I or IGF-II before it can complex with ALS to form the 150-kDa complex, we recently showed that unoccupied 150-kDa binary complexes of IGFBP-3 and ALS are abundant in adult rat serum.
404 7588232 We now demonstrate that IGFBP-3 and rat (r)ALS can form 150-kDa complexes in the absence of IGFs.
405 7588232 ALS was purified from rat serum by anion exchange chromatography and affinity chromatography on an IGF-I-Sepharose column to which human (h) IGFBP-3 had been noncovalently bound.
406 7588232 The preparation contained less than 0.1 ng IGF-I/microgram(s) purified ALS.
407 7588232 In this experiment IGFBP-3 binding was slightly increased by coincubation with IGF-I.
408 7588232 Purified rat acid-labile subunit and recombinant human insulin-like growth factor (IGF)-binding protein-3 can form a 150-kilodalton binary complex in vitro in the absence of IGFs.
409 7588232 Insulin-like growth factors (IGFs) circulate in plasma mainly as part of a 150-kilodalton (kDa) complex with 40- to 45-kDa IGF-binding protein-3 (IGFBP-3) and an approximately 85-kDa acid-labile subunit (ALS) that does not bind IGFs directly.
410 7588232 Although it has been thought that IGFBP-3 must first bind IGF-I or IGF-II before it can complex with ALS to form the 150-kDa complex, we recently showed that unoccupied 150-kDa binary complexes of IGFBP-3 and ALS are abundant in adult rat serum.
411 7588232 We now demonstrate that IGFBP-3 and rat (r)ALS can form 150-kDa complexes in the absence of IGFs.
412 7588232 ALS was purified from rat serum by anion exchange chromatography and affinity chromatography on an IGF-I-Sepharose column to which human (h) IGFBP-3 had been noncovalently bound.
413 7588232 The preparation contained less than 0.1 ng IGF-I/microgram(s) purified ALS.
414 7588232 In this experiment IGFBP-3 binding was slightly increased by coincubation with IGF-I.
415 7588232 Purified rat acid-labile subunit and recombinant human insulin-like growth factor (IGF)-binding protein-3 can form a 150-kilodalton binary complex in vitro in the absence of IGFs.
416 7588232 Insulin-like growth factors (IGFs) circulate in plasma mainly as part of a 150-kilodalton (kDa) complex with 40- to 45-kDa IGF-binding protein-3 (IGFBP-3) and an approximately 85-kDa acid-labile subunit (ALS) that does not bind IGFs directly.
417 7588232 Although it has been thought that IGFBP-3 must first bind IGF-I or IGF-II before it can complex with ALS to form the 150-kDa complex, we recently showed that unoccupied 150-kDa binary complexes of IGFBP-3 and ALS are abundant in adult rat serum.
418 7588232 We now demonstrate that IGFBP-3 and rat (r)ALS can form 150-kDa complexes in the absence of IGFs.
419 7588232 ALS was purified from rat serum by anion exchange chromatography and affinity chromatography on an IGF-I-Sepharose column to which human (h) IGFBP-3 had been noncovalently bound.
420 7588232 The preparation contained less than 0.1 ng IGF-I/microgram(s) purified ALS.
421 7588232 In this experiment IGFBP-3 binding was slightly increased by coincubation with IGF-I.
422 7593430 Portal insulin concentrations rather than insulin sensitivity regulate serum sex hormone-binding globulin and insulin-like growth factor binding protein 1 in vivo.
423 7593430 Serum sex hormone-binding globulin (SHBG) and insulin-like growth factor-binding protein 1 (IGFBP-1) concentrations have been suggested to be useful markers of insulin sensitivity.
424 7593430 To test this hypothesis, we determined SHBG and IGFBP-1 concentrations, whole body insulin sensitivity (euglycemic insulin clamp; serum free insulin, approximately 400 pmol/L), and serum insulin and C peptide concentrations in 13 type 1 diabetic patients lacking endogenous insulin secretion and 34 matched normal subjects.
425 7593430 Despite this, serum SHBG (45 +/- 4 vs. 29 +/- 2nmol/L; P < 0.002) and IGFBP-1 (14 +/- 3 vs. 2 +/- 1 micrograms/L; P < 0.002) concentrations were increased in the type 1 diabetic patients.
426 7593430 In the normal subjects, SHBG (r = -0.49; P < 0.01) and IGFBP-1 (r = -0.49; P < 0.01) were inversely correlated with serum C peptide and positively correlated with whole body insulin sensitivity (r = 0.54; P < 0.005 and r = 0.54; P < 0.005, respectively).
427 7593430 In the type 1 diabetic patients, SHBG and IGFBP-1 concentrations were disproportionately increased when related to insulin sensitivity, but appropriate when related to estimated portal insulin concentrations.
428 7593430 We conclude that SHBG and IGFBP-1 reflect hepatic insulinization and can only be used as markers of insulin sensitivity in individuals with intact insulin secretion.
429 7593430 Portal insulin concentrations rather than insulin sensitivity regulate serum sex hormone-binding globulin and insulin-like growth factor binding protein 1 in vivo.
430 7593430 Serum sex hormone-binding globulin (SHBG) and insulin-like growth factor-binding protein 1 (IGFBP-1) concentrations have been suggested to be useful markers of insulin sensitivity.
431 7593430 To test this hypothesis, we determined SHBG and IGFBP-1 concentrations, whole body insulin sensitivity (euglycemic insulin clamp; serum free insulin, approximately 400 pmol/L), and serum insulin and C peptide concentrations in 13 type 1 diabetic patients lacking endogenous insulin secretion and 34 matched normal subjects.
432 7593430 Despite this, serum SHBG (45 +/- 4 vs. 29 +/- 2nmol/L; P < 0.002) and IGFBP-1 (14 +/- 3 vs. 2 +/- 1 micrograms/L; P < 0.002) concentrations were increased in the type 1 diabetic patients.
433 7593430 In the normal subjects, SHBG (r = -0.49; P < 0.01) and IGFBP-1 (r = -0.49; P < 0.01) were inversely correlated with serum C peptide and positively correlated with whole body insulin sensitivity (r = 0.54; P < 0.005 and r = 0.54; P < 0.005, respectively).
434 7593430 In the type 1 diabetic patients, SHBG and IGFBP-1 concentrations were disproportionately increased when related to insulin sensitivity, but appropriate when related to estimated portal insulin concentrations.
435 7593430 We conclude that SHBG and IGFBP-1 reflect hepatic insulinization and can only be used as markers of insulin sensitivity in individuals with intact insulin secretion.
436 7595601 The insulin-like growth factor signaling system and ALS neurotrophic factor treatment strategies.
437 7595601 Because of its multi-faceted potential as a neurotrophic factor, insulin-like growth factor I (IGF-I) has been given to hundreds of ALS patients world-wide.
438 7595601 We found that about 25% of ALS patients in a controlled trial of human growth hormone (hGH) had lower or higher than normal IGF-I serum levels.
439 7595601 Many ALS patients do have some of the characteristics of type II diabetes mellitus, where IGF-I therapy is also under way.
440 7595601 In addition, in type I diabetes significant increase in a circulating molecule that binds IGF-I, IGF-I binding protein 1 (IGFBP-1), occurs along with reduced IGF-I, when neuropathic complications are prominent.
441 7595601 We have studied the response of IGFBPs in ALS patients to subcutaneous rhIGF-I and found transient induction of IGFBP-1.
442 7595601 However, the gene for another IGFBP, BP-2, co-localizes with the gene for juvenile ALS (ALSJ) on chromosome 2.
443 7595601 The insulin-like growth factor signaling system and ALS neurotrophic factor treatment strategies.
444 7595601 Because of its multi-faceted potential as a neurotrophic factor, insulin-like growth factor I (IGF-I) has been given to hundreds of ALS patients world-wide.
445 7595601 We found that about 25% of ALS patients in a controlled trial of human growth hormone (hGH) had lower or higher than normal IGF-I serum levels.
446 7595601 Many ALS patients do have some of the characteristics of type II diabetes mellitus, where IGF-I therapy is also under way.
447 7595601 In addition, in type I diabetes significant increase in a circulating molecule that binds IGF-I, IGF-I binding protein 1 (IGFBP-1), occurs along with reduced IGF-I, when neuropathic complications are prominent.
448 7595601 We have studied the response of IGFBPs in ALS patients to subcutaneous rhIGF-I and found transient induction of IGFBP-1.
449 7595601 However, the gene for another IGFBP, BP-2, co-localizes with the gene for juvenile ALS (ALSJ) on chromosome 2.
450 7595601 The insulin-like growth factor signaling system and ALS neurotrophic factor treatment strategies.
451 7595601 Because of its multi-faceted potential as a neurotrophic factor, insulin-like growth factor I (IGF-I) has been given to hundreds of ALS patients world-wide.
452 7595601 We found that about 25% of ALS patients in a controlled trial of human growth hormone (hGH) had lower or higher than normal IGF-I serum levels.
453 7595601 Many ALS patients do have some of the characteristics of type II diabetes mellitus, where IGF-I therapy is also under way.
454 7595601 In addition, in type I diabetes significant increase in a circulating molecule that binds IGF-I, IGF-I binding protein 1 (IGFBP-1), occurs along with reduced IGF-I, when neuropathic complications are prominent.
455 7595601 We have studied the response of IGFBPs in ALS patients to subcutaneous rhIGF-I and found transient induction of IGFBP-1.
456 7595601 However, the gene for another IGFBP, BP-2, co-localizes with the gene for juvenile ALS (ALSJ) on chromosome 2.
457 7595601 The insulin-like growth factor signaling system and ALS neurotrophic factor treatment strategies.
458 7595601 Because of its multi-faceted potential as a neurotrophic factor, insulin-like growth factor I (IGF-I) has been given to hundreds of ALS patients world-wide.
459 7595601 We found that about 25% of ALS patients in a controlled trial of human growth hormone (hGH) had lower or higher than normal IGF-I serum levels.
460 7595601 Many ALS patients do have some of the characteristics of type II diabetes mellitus, where IGF-I therapy is also under way.
461 7595601 In addition, in type I diabetes significant increase in a circulating molecule that binds IGF-I, IGF-I binding protein 1 (IGFBP-1), occurs along with reduced IGF-I, when neuropathic complications are prominent.
462 7595601 We have studied the response of IGFBPs in ALS patients to subcutaneous rhIGF-I and found transient induction of IGFBP-1.
463 7595601 However, the gene for another IGFBP, BP-2, co-localizes with the gene for juvenile ALS (ALSJ) on chromosome 2.
464 7595601 The insulin-like growth factor signaling system and ALS neurotrophic factor treatment strategies.
465 7595601 Because of its multi-faceted potential as a neurotrophic factor, insulin-like growth factor I (IGF-I) has been given to hundreds of ALS patients world-wide.
466 7595601 We found that about 25% of ALS patients in a controlled trial of human growth hormone (hGH) had lower or higher than normal IGF-I serum levels.
467 7595601 Many ALS patients do have some of the characteristics of type II diabetes mellitus, where IGF-I therapy is also under way.
468 7595601 In addition, in type I diabetes significant increase in a circulating molecule that binds IGF-I, IGF-I binding protein 1 (IGFBP-1), occurs along with reduced IGF-I, when neuropathic complications are prominent.
469 7595601 We have studied the response of IGFBPs in ALS patients to subcutaneous rhIGF-I and found transient induction of IGFBP-1.
470 7595601 However, the gene for another IGFBP, BP-2, co-localizes with the gene for juvenile ALS (ALSJ) on chromosome 2.
471 7595601 The insulin-like growth factor signaling system and ALS neurotrophic factor treatment strategies.
472 7595601 Because of its multi-faceted potential as a neurotrophic factor, insulin-like growth factor I (IGF-I) has been given to hundreds of ALS patients world-wide.
473 7595601 We found that about 25% of ALS patients in a controlled trial of human growth hormone (hGH) had lower or higher than normal IGF-I serum levels.
474 7595601 Many ALS patients do have some of the characteristics of type II diabetes mellitus, where IGF-I therapy is also under way.
475 7595601 In addition, in type I diabetes significant increase in a circulating molecule that binds IGF-I, IGF-I binding protein 1 (IGFBP-1), occurs along with reduced IGF-I, when neuropathic complications are prominent.
476 7595601 We have studied the response of IGFBPs in ALS patients to subcutaneous rhIGF-I and found transient induction of IGFBP-1.
477 7595601 However, the gene for another IGFBP, BP-2, co-localizes with the gene for juvenile ALS (ALSJ) on chromosome 2.
478 7679899 Structure of the rat insulin-like growth factor binding protein-4 gene.
479 7679899 A family of six distinct insulin-like growth factor binding proteins (IGFBPs) have been isolated and their cDNA sequences characterized from rat and human species.
480 7679899 The rat IGFBP-4 gene possesses a typical TATA box and a CAAT box, as well as multiple potential cis elements, including three cAMP responsive elements, three AP-1 binding sites and one progesterone receptor binding site in the 5' flanking region.
481 7679898 Cloning of the rat insulin- like growth factor binding protein-5 gene and DNA sequence analysis of its promoter region.
482 7679898 To understand the regulation of the insulin-like growth factor binding protein-5 (IGFBP-5) gene expression, we have cloned the IGFBP-5 gene from rat genomic libraries and determined its genomic organization as well as the DNA sequence at the 5' flanking region of the gene.
483 7679898 In addition to a TATA box and a CAAT box, multiple putative cis-regulatory elements, including an AP-1, an AP-2 and a binding site for progesterone receptor are present in the promoter region.
484 7679898 Cloning of the rat insulin- like growth factor binding protein-5 gene and DNA sequence analysis of its promoter region.
485 7679898 To understand the regulation of the insulin-like growth factor binding protein-5 (IGFBP-5) gene expression, we have cloned the IGFBP-5 gene from rat genomic libraries and determined its genomic organization as well as the DNA sequence at the 5' flanking region of the gene.
486 7679898 In addition to a TATA box and a CAAT box, multiple putative cis-regulatory elements, including an AP-1, an AP-2 and a binding site for progesterone receptor are present in the promoter region.
487 7681467 Insulin-like growth factor-binding protein-1, glucose tolerance and fetal growth in human pregnancy.
488 7681467 In 149 women, a single sample was taken for insulin-like growth factor-binding protein-1 (IGFBP-1) measurement 0, 1, 2 or 3 h after the glucose load at both visits; in 55 women IGFBP-1 levels were estimated in all four OGTT samples.
489 7681467 Insulin-like growth factor-binding protein-1, glucose tolerance and fetal growth in human pregnancy.
490 7681467 In 149 women, a single sample was taken for insulin-like growth factor-binding protein-1 (IGFBP-1) measurement 0, 1, 2 or 3 h after the glucose load at both visits; in 55 women IGFBP-1 levels were estimated in all four OGTT samples.
491 7682065 Structural characterization of the rat insulin-like growth factor binding protein-6 gene.
492 7682065 Recently a family of six distinct insulin-like growth factor binding proteins (IGFBPs) have been identified and the gene structures of the first five (IGFBP-1, -2, -3, -4 and -5) characterized.
493 7682065 The promoter region of the rat IGFBP-6 gene is devoid of a TATA or a CAAT consensus sequence motif, but putative regulatory cis elements, including a Sp1, an estrogen receptor binding site and a retinoic acid responsive element, are present in the promoter region.
494 7683533 Human insulin-like growth factor binding protein-6 is O-glycosylated.
495 7683533 Insulin-like growth factor binding protein-6 (IGFBP-6) is found in serum, cerebrospinal fluid and conditioned media from human fibroblasts.
496 7683533 It has a marked preferential binding affinity for IGF-II over IGF-I.
497 7683533 Enzymatic deglycosylation does not alter the high affinity of IGFBP-6 for IGF-II (Ka 4.4 +/- 2.2 x 10(11) M-1) or its preference for IGF-II over IGF-I.
498 7683533 Human insulin-like growth factor binding protein-6 is O-glycosylated.
499 7683533 Insulin-like growth factor binding protein-6 (IGFBP-6) is found in serum, cerebrospinal fluid and conditioned media from human fibroblasts.
500 7683533 It has a marked preferential binding affinity for IGF-II over IGF-I.
501 7683533 Enzymatic deglycosylation does not alter the high affinity of IGFBP-6 for IGF-II (Ka 4.4 +/- 2.2 x 10(11) M-1) or its preference for IGF-II over IGF-I.
502 7683739 Insulin-like growth factor-binding protein-1 response to insulin during suppression of endogenous insulin secretion.
503 7683739 Insulin-like growth factor-binding protein-1 (IGFBP-1) is one of several related proteins that bind and modulate the actions of IGFs.
504 7683739 The liver is the primary source of IGFBP-1, and insulin is a major regulator of hepatic IGFBP-1 production.
505 7683739 In normal subjects, a continuous high-dose insulin infusion caused a rapid decrease in plasma IGFBP-1 concentrations, with a rate of 0.24 +/- 0.04 microgram/L.min-1 and a t1/2 of 89 +/- 4 minutes.
506 7683739 Conversely, a 3-hour somatostatin (SRIF) infusion caused a 4.5-fold increase in plasma IGFBP-1 levels.
507 7683739 SRIF plus low-dose insulin infusion (to inhibit break-through insulin secretion) resulted in a plateau in IGFBP-1 concentrations at 5 to 8 hours, with a t1/2 to achieve steady state of 60 to 75 minutes.
508 7683739 Under similar conditions, a stepped increase in plasma glucose level from 5 to 9 mmol/L had no effect on the rate of IGFBP-1 increase in plasma, indicating that an acute increase in glucose concentration within a physiologic range has no independent inhibitory effect on IGFBP-1 production in the presence of a nonsuppressive insulin level.
509 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.
510 7683739 Subjects with insulin-dependent diabetes mellitus (IDDM) showed a similar dose-response pattern, suggesting that insulin regulation of IGFBP-1 may be normal in IDDM.
511 7683739 Insulin-like growth factor-binding protein-1 response to insulin during suppression of endogenous insulin secretion.
512 7683739 Insulin-like growth factor-binding protein-1 (IGFBP-1) is one of several related proteins that bind and modulate the actions of IGFs.
513 7683739 The liver is the primary source of IGFBP-1, and insulin is a major regulator of hepatic IGFBP-1 production.
514 7683739 In normal subjects, a continuous high-dose insulin infusion caused a rapid decrease in plasma IGFBP-1 concentrations, with a rate of 0.24 +/- 0.04 microgram/L.min-1 and a t1/2 of 89 +/- 4 minutes.
515 7683739 Conversely, a 3-hour somatostatin (SRIF) infusion caused a 4.5-fold increase in plasma IGFBP-1 levels.
516 7683739 SRIF plus low-dose insulin infusion (to inhibit break-through insulin secretion) resulted in a plateau in IGFBP-1 concentrations at 5 to 8 hours, with a t1/2 to achieve steady state of 60 to 75 minutes.
517 7683739 Under similar conditions, a stepped increase in plasma glucose level from 5 to 9 mmol/L had no effect on the rate of IGFBP-1 increase in plasma, indicating that an acute increase in glucose concentration within a physiologic range has no independent inhibitory effect on IGFBP-1 production in the presence of a nonsuppressive insulin level.
518 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.
519 7683739 Subjects with insulin-dependent diabetes mellitus (IDDM) showed a similar dose-response pattern, suggesting that insulin regulation of IGFBP-1 may be normal in IDDM.
520 7686482 Cyclic adenosine monophosphate stimulates insulin-like growth factor binding protein-4 and its messenger ribonucleic acid in a clonal endothelial cell line.
521 7686482 Endothelial cells regulate the passage of insulin-like growth factors (IGFs) or IGFs complexed to IGF-binding proteins (IGFBPs) from plasma to the extravascular space, and in addition respond to plasma and tissue IGFs.
522 7686482 Northern blot hybridization of BPE-1 RNA identified messenger RNAs for IGFBP-4 and IGFBP-6, but not for IGFBP-1, 2, 3, or 5.
523 7687409 C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in umbilical cord serum: correlations with birth weight.
524 7688338 Insulin-like growth factor binding protein-1 levels in diabetic proliferative retinopathy.
525 7688368 Cycloheximide stabilizes insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and inhibits IGFBP-1 transcription in H4-II-E rat hepatoma cells.
526 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.
527 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.
528 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.
529 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.
530 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.
531 7689963 Rat PC12 pheochromocytoma cells synthesize insulin-like growth factor-binding protein-6.
532 7689963 Insulin-like growth factor-I (IGF-I) and IGF-II are mitogenic for PC12 cells under serum-starved conditions.
533 7689963 It recently was reported that PC12 cells produced an IGFBP that had a marked preferential binding affinity for IGF-II over IGF-I.
534 7689963 Rat IGFBP-6, like human IGFBP-6, is O-glycosylated; incubation with neuraminidase, fucosidase, and O-glycanase reduced its apparent molecular mass to 21 kilodaltons.
535 7689963 Competitive binding studies of rat and human IGFBP-6 with [125I]IGF-II and unlabeled IGF-II or IGF-I demonstrated that both IGFBPs bound IGF-II with similar affinities (Ka, 1.5-1.8 x 10(11) M-1) and bound IGF-I with approximately 25- to 35-fold lower affinity than IGF-II.
536 7693708 Three clustered Sp1 sites are required for efficient transcription of the TATA-less promoter of the gene for insulin-like growth factor-binding protein-2 from the rat.
537 7693708 Insulin-like growth factor-binding protein-2 (IGF-BP-2) transcription in rat liver varies with developmental age and fasting.
538 7693708 In DNase I foot-printing assays using native nt -276 to -36 promoter fragments or fragments containing block substitution mutations, BRL-3A nuclear extract and purified human transcription factor Sp1 protected a region from nt -234 to -215 containing one GC box and a broad region from nt -189 to -125 that contained three clustered but independent GC boxes.
539 7693708 The proximal three GC boxes were sufficient to allow trans-activation of the IGFBP-2 promoter by Sp1 in Drosophila SL2 cells.
540 7693708 Thus, binding of Sp1 or Sp1-related proteins to three clustered GC boxes in the proximal IGFBP-2 promoter is essential for promoter activity.
541 7693708 Three clustered Sp1 sites are required for efficient transcription of the TATA-less promoter of the gene for insulin-like growth factor-binding protein-2 from the rat.
542 7693708 Insulin-like growth factor-binding protein-2 (IGF-BP-2) transcription in rat liver varies with developmental age and fasting.
543 7693708 In DNase I foot-printing assays using native nt -276 to -36 promoter fragments or fragments containing block substitution mutations, BRL-3A nuclear extract and purified human transcription factor Sp1 protected a region from nt -234 to -215 containing one GC box and a broad region from nt -189 to -125 that contained three clustered but independent GC boxes.
544 7693708 The proximal three GC boxes were sufficient to allow trans-activation of the IGFBP-2 promoter by Sp1 in Drosophila SL2 cells.
545 7693708 Thus, binding of Sp1 or Sp1-related proteins to three clustered GC boxes in the proximal IGFBP-2 promoter is essential for promoter activity.
546 7694822 Insulin-like growth-factor binding protein (IGFBP) serum levels and hepatic IGFBP-2 and -3 mRNA expression in diabetic and insulin-treated swine (Sus scrofa).
547 7694822 Diabetes had no significant effect on IGFBP-3 message and serum levels however, subsequent insulin treatment caused more than a two-fold increase in both hepatic IGFBP-3 mRNA and serum levels above controls (P < 0.05). 2.
548 7694822 Both liver message and serum IGFBP-2 were reduced to control levels with insulin therapy. 4.
549 7694822 We report here that in addition to its affects on IGFBP-2, insulin is involved in the regulation of IGFBP-3 expression.
550 7694841 Effects of glucocorticoids on circulating levels and hepatic expression of insulin-like growth factor (IGF)-binding proteins and IGF-I in the adrenalectomized streptozotocin-diabetic rat.
551 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.
552 7694841 Glucocorticoids stimulate and insulin suppresses hepatocellular expression of IGFBP-1 in vitro.
553 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.
554 7694841 Serum [125I]IGF-I-binding activity was increased 4-fold (P < 0.01), and Western ligand and immunoblotting demonstrated that levels of IGFBP-1 were high in intact STZ-diabetic animals.
555 7694841 Corticosterone treatment restored hepatic IGFBP-1 mRNA to intact diabetic levels, and serum concentrations of corticosterone correlated with the abundance of IGFBP-1 mRNA (r = 0.475; P < 0.01), indicating that glucocorticoids play an important role in the regulation of expression of IGFBP-1 in insulin-deficient animals.
556 7694841 This pattern of regulation appeared to be specific; serum levels of immunoreactive IGFBP-2 and -4 tended to rise in adrenalectomized animals, and levels of IGFBP-3 were not affected by either ADNX or corticosterone treatment.
557 7694841 Of note, serum levels of IGF-I by RIA were reduced in STZ-diabetic animals compared to control values (168 +/- 16 vs. 587 +/- 55 ng/ml, respectively; P < 0.01), were partially restored toward control values with ADNX (320 +/- 22 ng/ml), and were reduced again by corticosterone treatment (195 +/- 26 ng/ml), indicating that glucocorticoids also contribute to the regulation of IGF-I levels in insulin-deficient animals.
558 7756975 Increased kidney and liver insulin-like growth factor II/mannose-6-phosphate receptor concentration in experimental diabetes in rats.
559 7756975 Diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I and insulin-like growth factor binding protein concentration suggesting a renotropic function in diabetic kidney growth.
560 7756975 In order to further examine the possible involvement of the insulin-like growth factor system in initial diabetic kidney growth, we have studied the expression of the kidney insulin-like growth factor II/mannose-6-phosphate receptor during the first 4 days after induction of diabetes in rats.
561 7756975 Using a specific antiserum (#3637) raised against the insulin-like growth factor II/mannose-6-phosphate receptor of rat chondrosarcoma a specific band with an apparent molecular weight of 220 kDa was identified in Western blotting experiments with kidney and liver protein extracts.
562 7756975 In untreated diabetic rats a transient increase of the kidney and liver insulin-like growth factor II/mannose-6-phosphate receptor concentration was measured 24-48 h after the induction of diabetes (mean increase in kidney 140% and liver 112%, n = 5).
563 7756975 This increase was followed by a subsequent decrease in the insulin-like growth factor II/mannose-6-phosphate receptor protein concentration after 3-4 days of diabetes.
564 7756975 In conclusion, the present study shows a transient increase of insulin-like growth factor II/mannose-6-phosphate receptor concentration in hypertrophying diabetic kidneys and in diabetic livers, contemporarily with the previously described increase in kidney insulin-like growth factor I and insulin-like growth factor binding protein content.
565 7756975 Increased kidney and liver insulin-like growth factor II/mannose-6-phosphate receptor concentration in experimental diabetes in rats.
566 7756975 Diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I and insulin-like growth factor binding protein concentration suggesting a renotropic function in diabetic kidney growth.
567 7756975 In order to further examine the possible involvement of the insulin-like growth factor system in initial diabetic kidney growth, we have studied the expression of the kidney insulin-like growth factor II/mannose-6-phosphate receptor during the first 4 days after induction of diabetes in rats.
568 7756975 Using a specific antiserum (#3637) raised against the insulin-like growth factor II/mannose-6-phosphate receptor of rat chondrosarcoma a specific band with an apparent molecular weight of 220 kDa was identified in Western blotting experiments with kidney and liver protein extracts.
569 7756975 In untreated diabetic rats a transient increase of the kidney and liver insulin-like growth factor II/mannose-6-phosphate receptor concentration was measured 24-48 h after the induction of diabetes (mean increase in kidney 140% and liver 112%, n = 5).
570 7756975 This increase was followed by a subsequent decrease in the insulin-like growth factor II/mannose-6-phosphate receptor protein concentration after 3-4 days of diabetes.
571 7756975 In conclusion, the present study shows a transient increase of insulin-like growth factor II/mannose-6-phosphate receptor concentration in hypertrophying diabetic kidneys and in diabetic livers, contemporarily with the previously described increase in kidney insulin-like growth factor I and insulin-like growth factor binding protein content.
572 8088124 A fasting blood sample was obtained from subjects with Type 1 diabetes for the measurement of ovarian and adrenal sex hormones, LH and FSH, glucose and insulin, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-1 (IGFBP-1); and an ovarian ultrasound scan was performed.
573 8088124 Subjects with Type 1 diabetes with irregular menses (when compared with diabetic subjects with a regular cycle) had a significantly higher HbA1 (12.8 +/- 0.4 vs 10.5 +/- 0.5%, p < 0.01) and BMI (23.2 +/- 0.6 vs 21.4 +/- 0.6 kg m-2, p < 0.05) associated with a lower sex hormone binding globulin (SHBG) (37.2 +/- 4.0 vs 52.6 +/- 4.0 nmol l-1, p < 0.025) and IGF-I (1.4 +/- 0.2 vs 2.2 +/- 0.2 mUI-1, p < 0.025) and a higher LH:FSH ratio (2.6 +/- 0.5 vs 1.4 +/- 0.2, p < 0.05).
574 8530614 Insulin-like growth factor-binding protein-2 and insulin: studies in children with type 1 diabetes mellitus and maturity-onset diabetes of the young.
575 8530614 The regulation of circulating insulin-like growth factor-binding protein-2 (IGFBP-2) in humans is not well understood.
576 8530614 In vitro and animal data have identified the role of insulin in the regulation of IGFBP-2, but such a relationship has not been established clearly in humans.
577 8530614 In the present study, serum IGFBP-2 concentrations were assessed by Western ligand blot and immunoblot analysis in children with newly diagnosed and untreated insulin-dependent diabetes mellitus (IDDM) and maturity-onset diabetes of the young before and at various times after insulin therapy.
578 8530614 Densitometric analysis demonstrated that before insulin therapy, group A patients had serum IGFBP-2 levels comparable to those in lean controls, and no significant change in IGFBP-2 was observed during insulin therapy.
579 8530614 However, group B patients had a 2-fold elevation in IGFBP-2 levels before insulin therapy compared to lean controls.
580 8530614 In these patients, IGFBP-2 tended to decrease at 1 week, but was not significantly reduced until 1 month after the initiation of insulin therapy.
581 8530614 Children with maturity-onset diabetes of the young, who had insulin levels and body mass indexes greater than IDDM patients and lean controls, had significantly lower IGFBP-2 levels than both lean and obese controls.
582 8530614 IGFBP-2 levels tended to decrease further during insulin therapy.
583 8530614 These results indicate that long standing alterations in serum insulin concentrations beyond the physiological range have significant influence on serum IGFBP-2 levels in children and confirm earlier findings that serum IGFBP-2 levels are not acutely regulated by insulin.
584 8530614 Insulin-like growth factor-binding protein-2 and insulin: studies in children with type 1 diabetes mellitus and maturity-onset diabetes of the young.
585 8530614 The regulation of circulating insulin-like growth factor-binding protein-2 (IGFBP-2) in humans is not well understood.
586 8530614 In vitro and animal data have identified the role of insulin in the regulation of IGFBP-2, but such a relationship has not been established clearly in humans.
587 8530614 In the present study, serum IGFBP-2 concentrations were assessed by Western ligand blot and immunoblot analysis in children with newly diagnosed and untreated insulin-dependent diabetes mellitus (IDDM) and maturity-onset diabetes of the young before and at various times after insulin therapy.
588 8530614 Densitometric analysis demonstrated that before insulin therapy, group A patients had serum IGFBP-2 levels comparable to those in lean controls, and no significant change in IGFBP-2 was observed during insulin therapy.
589 8530614 However, group B patients had a 2-fold elevation in IGFBP-2 levels before insulin therapy compared to lean controls.
590 8530614 In these patients, IGFBP-2 tended to decrease at 1 week, but was not significantly reduced until 1 month after the initiation of insulin therapy.
591 8530614 Children with maturity-onset diabetes of the young, who had insulin levels and body mass indexes greater than IDDM patients and lean controls, had significantly lower IGFBP-2 levels than both lean and obese controls.
592 8530614 IGFBP-2 levels tended to decrease further during insulin therapy.
593 8530614 These results indicate that long standing alterations in serum insulin concentrations beyond the physiological range have significant influence on serum IGFBP-2 levels in children and confirm earlier findings that serum IGFBP-2 levels are not acutely regulated by insulin.
594 8548941 The 'dawn phenomenon' in adolescents with insulin dependent diabetes mellitus: possible contribution of insulin-like growth factor binding protein-1.
595 8636318 Reduced insulin-like growth factor binding protein-1 (IGFBP-1) levels correlate with increased cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM).
596 8636318 We examined cardiovascular risk factors, IGF-I, IGF-II and IGFBP-1 in 74 NIDDM patients analysed as a whole group and according to treatment type.
597 8636318 IGF-I was not significantly associated with cardiovascular risk factors but IGF-II levels correlated positively with total and LDL cholesterol most markedly in the diet treated group (0.72, p < 0.01 and 0.76, p < 0.01 respectively).
598 8636318 In the whole group reduced IGFBP-1 levels were significantly associated with factors known to increase cardiovascular risk: i.e. low HDL cholesterol (0.31, p < 0.01) and elevated blood pressure (-0.35, p < 0.01), BMI (-0.37, p < 0.01), insulin (-0.29, p < 0.01) and proinsulin (-0.24, p < 0.01).
599 8636318 In the treatment groups IGFBP-1 was lower in patients on diet alone (n = 11, 42.6 +/- 11.6 mu g/l) and sulphonylurea +/- insulin (n = 39, 53.2 +/- 7.6 mu g/l) relative to insulin treatment (n = 24, 103.0 +/- 19, 7 mu g/l, p < 0.05).
600 8707251 High insulin-like growth factor binding protein 1 levels in cirrhosis: link with insulin resistance.
601 8707251 The cirrhotic patients had high growth hormone (GH) and low insulin-like growth factor-I (IGF-I) levels, with low insulin-like growth factor-binding protein (IGFBP)-3 levels, but surprisingly high IGFBP-I levels (26.8 +/- 8.4 microgH vs. 3.2 +/- 0.2 microm/L, P < .001).
602 8707251 The log IGFBP-1 level was inversely correlated with the log insulin sensitivity (r = -.95).
603 8707251 GH, IGF-1, and IGFBP-3 levels were now similar in the two groups; IGFBP-1 levels decreased in the cirrhotic patients but remained fivefold higher than the comparison value (10.6 +/- 3.7 vs. 2.1 +/- 0.4, P < .05).
604 8707251 These results suggests an important role for IGFBP-1 in modulating insulin sensitivity in cirrhosis.
605 8707251 High insulin-like growth factor binding protein 1 levels in cirrhosis: link with insulin resistance.
606 8707251 The cirrhotic patients had high growth hormone (GH) and low insulin-like growth factor-I (IGF-I) levels, with low insulin-like growth factor-binding protein (IGFBP)-3 levels, but surprisingly high IGFBP-I levels (26.8 +/- 8.4 microgH vs. 3.2 +/- 0.2 microm/L, P < .001).
607 8707251 The log IGFBP-1 level was inversely correlated with the log insulin sensitivity (r = -.95).
608 8707251 GH, IGF-1, and IGFBP-3 levels were now similar in the two groups; IGFBP-1 levels decreased in the cirrhotic patients but remained fivefold higher than the comparison value (10.6 +/- 3.7 vs. 2.1 +/- 0.4, P < .05).
609 8707251 These results suggests an important role for IGFBP-1 in modulating insulin sensitivity in cirrhosis.
610 8770014 The effect of refeeding and insulin treatment of undernourished and diabetic neonatal rats, respectively, on the regulation of insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) was investigated.
611 8770014 The changes in body weight, insulinemia, glycemia, serum IGF-I, and growth hormone (GH) as well as the increase of the 30-kDa IGFBP in undernourished and diabetic neonatal rats previously shown elsewhere were reversed by refeeding and insulin treatment, respectively.
612 8770014 Also, changes in liver mRNA expression of IGF-I and-II and IGFBP-1 and -2 were restored in refed undernourished and IGF-I and IGFBP-1 levels recovered in insulin-treated diabetic rats.
613 8776722 Insulin and insulin-like growth factor-I regulate hepatic insulin-like growth factor binding protein-3 by different mechanisms.
614 8817654 Dexamethasone stimulation of rat insulin-like growth factor binding protein-1 (IGFBP-1) promoter activity involves the interaction of multiple transcription factors.
615 8817654 Using an improved procedure for transient transfection of H4-II-E rat hepatoma cells, we characterized the cis elements in the proximal promoter of the rat insulin-like growth factor binding protein-1 (rat IGFBP-1) gene that are required for basal (unstimulated) and dexamethasone-stimulated promoter activity.
616 8817654 Three sites are required for optimal basal promoter activity: an AP-2 site (nt -286 to -293), the M4 region of the insulin response element (nt -108 to -99), and a hepatocyte nuclear factor-1 (HNF-1) site (nt -62 to -50).
617 8817654 Dexamethasone stimulation of rat insulin-like growth factor binding protein-1 (IGFBP-1) promoter activity involves the interaction of multiple transcription factors.
618 8817654 Using an improved procedure for transient transfection of H4-II-E rat hepatoma cells, we characterized the cis elements in the proximal promoter of the rat insulin-like growth factor binding protein-1 (rat IGFBP-1) gene that are required for basal (unstimulated) and dexamethasone-stimulated promoter activity.
619 8817654 Three sites are required for optimal basal promoter activity: an AP-2 site (nt -286 to -293), the M4 region of the insulin response element (nt -108 to -99), and a hepatocyte nuclear factor-1 (HNF-1) site (nt -62 to -50).
620 8817667 Formation of 150-kDa binary complexes of insulin-like growth factor binding protein-3 and the acid-labile subunit in vitro and in vivo.
621 8817667 Adult rat serum contains two types of 150-kDa IGFBP complexes: ternary complexes containing bound IGF-I, intact IGFBP-3 and the acid-labile subunit (ALS), and binary complexes that contain ALS and proteolytically-nicked IGFBP-3 but which lack bound IGF.
622 8817667 We present evidence that the binary complexes containing proteolytically-nicked IGFBP-3 can be formed in two ways: by direct association of IGFBP-3 with ALS in the absence of IGF, and by proteolysis of IGFBP-3 within 150-kDa ternary complexes, resulting in increased dissociation of IGF-I.
623 8817667 Proteolysis of IGFBP-3 in the 150-kDa ternary complex provides a regulatable mechanism by which IGF-I may be mobilized from the circulating reservoir of 150-kDa complexes to the tissues.
624 8817667 Formation of 150-kDa binary complexes of insulin-like growth factor binding protein-3 and the acid-labile subunit in vitro and in vivo.
625 8817667 Adult rat serum contains two types of 150-kDa IGFBP complexes: ternary complexes containing bound IGF-I, intact IGFBP-3 and the acid-labile subunit (ALS), and binary complexes that contain ALS and proteolytically-nicked IGFBP-3 but which lack bound IGF.
626 8817667 We present evidence that the binary complexes containing proteolytically-nicked IGFBP-3 can be formed in two ways: by direct association of IGFBP-3 with ALS in the absence of IGF, and by proteolysis of IGFBP-3 within 150-kDa ternary complexes, resulting in increased dissociation of IGF-I.
627 8817667 Proteolysis of IGFBP-3 in the 150-kDa ternary complex provides a regulatable mechanism by which IGF-I may be mobilized from the circulating reservoir of 150-kDa complexes to the tissues.
628 8817667 Formation of 150-kDa binary complexes of insulin-like growth factor binding protein-3 and the acid-labile subunit in vitro and in vivo.
629 8817667 Adult rat serum contains two types of 150-kDa IGFBP complexes: ternary complexes containing bound IGF-I, intact IGFBP-3 and the acid-labile subunit (ALS), and binary complexes that contain ALS and proteolytically-nicked IGFBP-3 but which lack bound IGF.
630 8817667 We present evidence that the binary complexes containing proteolytically-nicked IGFBP-3 can be formed in two ways: by direct association of IGFBP-3 with ALS in the absence of IGF, and by proteolysis of IGFBP-3 within 150-kDa ternary complexes, resulting in increased dissociation of IGF-I.
631 8817667 Proteolysis of IGFBP-3 in the 150-kDa ternary complex provides a regulatable mechanism by which IGF-I may be mobilized from the circulating reservoir of 150-kDa complexes to the tissues.
632 8817687 Insulin-like growth factor-I and insulin-like growth factor binding protein-3 inhibit involution of the mammary gland following lactation: studies in transgenic mice.
633 8817687 The role of the insulin-like growth factor system on mammary gland development and involution following pregnancy and lactation was studied.
634 8817687 Transgenic mice expressing rat IGF-I and human IGFBP-3 specifically in the mammary gland tissue, were created using the whey acidic protein gene.
635 8828497 Heparin inhibition of insulin-like growth factor-binding protein-3 binding to human fibroblasts and rat glioma cells: role of heparan sulfate proteoglycans.
636 8828497 The mitogenic action of insulin-like growth factors (IGFs) on target cells is determined by interaction with signaling IGF-I receptors and modulated by interactions with IGF-binding proteins (IGFBPs).
637 8828497 IGFBP-3, an abundant IGFBP that binds IGF-I and IGF-II with high affinity, can form soluble inhibitory complexes with the IGFs that prevent them from binding to IGF-I receptors.
638 8828497 Complete digestion of cell surface heparan sulfate and chondroitin sulfate glycosaminoglycans using heparitinase and chondroitinase ABC, however, did not significantly decrease IGFBP-3 binding.
639 8828497 These results suggest that direct interaction of heparin or IGF-I with IGFBP-3 inhibits its ability to bind to the surface of GM-10 fibroblasts and C6 glioma cells.
640 8846679 The effects of repeated daily recombinant human insulin-like growth factor I administration in adolescents with type 1 diabetes.
641 8846679 Reduced insulin-like growth factor bioactivity has been linked to poor metabolic control and growth hormone hypersecretion in adolescents with Type 1 diabetes.
642 8846679 The safety and efficacy of recombinant human insulin-like growth factor I administered subcutaneously in a dose of 40 micrograms kg-1 for 28 days was studied in a group of 6 adolescent male subjects with Type 1 diabetes (aged 13.6-19.4 years, puberty stage 3-5).
643 8846679 After a 4-week run-in period (week -4 day 0) recombinant human insulin-like growth factor I was administered for 4 weeks (day 0 to week +4) before a run-out of a further 4 weeks duration (week +4 to +8).
644 8846679 HbA1c levels were measured throughout the study and overnight profiles were undertaken to study levels of insulin-like growth factor 1, insulin-like growth factor binding protein-3, and growth hormone concentrations (week -1, day 0, and week +4).
645 8846679 Recombinant insulin-like growth factor I administration appeared to lead to a sustained increase in insulin-like growth factor I levels (week -1; 198 +/- 16 ng ml-1, week +4; 422 +/- 18 ng ml-1, mean +/- SEM; p = 0.03).
646 8846679 Insulin-like growth factor binding protein-3 concentrations (n = 6) increased in 5 subjects (week -1; 4.5 +/- 0.3 micrograms ml-1, week +4; 5.1 +/- 0.4 micrograms ml-1) and mean overnight growth hormone decreased (week -1; 14.0 +/- 3.1 mUI-1, week +4; 7.6 +/- 1.7 mUI-1) during the period of study but these differences were not statistically significant.
647 8846679 The effects of repeated daily recombinant human insulin-like growth factor I administration in adolescents with type 1 diabetes.
648 8846679 Reduced insulin-like growth factor bioactivity has been linked to poor metabolic control and growth hormone hypersecretion in adolescents with Type 1 diabetes.
649 8846679 The safety and efficacy of recombinant human insulin-like growth factor I administered subcutaneously in a dose of 40 micrograms kg-1 for 28 days was studied in a group of 6 adolescent male subjects with Type 1 diabetes (aged 13.6-19.4 years, puberty stage 3-5).
650 8846679 After a 4-week run-in period (week -4 day 0) recombinant human insulin-like growth factor I was administered for 4 weeks (day 0 to week +4) before a run-out of a further 4 weeks duration (week +4 to +8).
651 8846679 HbA1c levels were measured throughout the study and overnight profiles were undertaken to study levels of insulin-like growth factor 1, insulin-like growth factor binding protein-3, and growth hormone concentrations (week -1, day 0, and week +4).
652 8846679 Recombinant insulin-like growth factor I administration appeared to lead to a sustained increase in insulin-like growth factor I levels (week -1; 198 +/- 16 ng ml-1, week +4; 422 +/- 18 ng ml-1, mean +/- SEM; p = 0.03).
653 8846679 Insulin-like growth factor binding protein-3 concentrations (n = 6) increased in 5 subjects (week -1; 4.5 +/- 0.3 micrograms ml-1, week +4; 5.1 +/- 0.4 micrograms ml-1) and mean overnight growth hormone decreased (week -1; 14.0 +/- 3.1 mUI-1, week +4; 7.6 +/- 1.7 mUI-1) during the period of study but these differences were not statistically significant.
654 8865877 Serum insulin and insulin-like growth factor binding protein-1 levels in adult patients undergoing peritoneal dialysis.
655 8865877 It is known that serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations are inversely related to insulin levels both in healthy and diabetic subjects.
656 8865877 The aim of the present study was to assess serum IGFBP-1 levels in a group of patients undergoing peritoneal dialysis (PD) and to evaluate their relationship with serum insulin concentrations.
657 8865877 In all patients, baseline IGFBP-1, insulin, and growth hormone (GH) levels were determined.
658 8865877 There was no correlation between fasting insulin and IGFBP-1 levels both in the whole group (r = 0.2; NS) and the diabetic (r = 0.2; NS) and nondiabetic (r = 0.3; NS) subgroups, despite high fasting insulin levels.
659 8865877 This suggests that insulin does not affect IGFBP-1 production in this group of patients.
660 8865877 Serum insulin and insulin-like growth factor binding protein-1 levels in adult patients undergoing peritoneal dialysis.
661 8865877 It is known that serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations are inversely related to insulin levels both in healthy and diabetic subjects.
662 8865877 The aim of the present study was to assess serum IGFBP-1 levels in a group of patients undergoing peritoneal dialysis (PD) and to evaluate their relationship with serum insulin concentrations.
663 8865877 In all patients, baseline IGFBP-1, insulin, and growth hormone (GH) levels were determined.
664 8865877 There was no correlation between fasting insulin and IGFBP-1 levels both in the whole group (r = 0.2; NS) and the diabetic (r = 0.2; NS) and nondiabetic (r = 0.3; NS) subgroups, despite high fasting insulin levels.
665 8865877 This suggests that insulin does not affect IGFBP-1 production in this group of patients.
666 8910817 Serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in children with insulin-dependent diabetes mellitus.
667 8910817 Pubertal development has recently been evaluated from the standpoint of changes in insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) levels in healthy children.
668 8910817 We studied puberty related changes in serum IGF-I and IGFBP-3 levels in 24 patients (11 prepubertal) with insulin dependent diabetes mellitus (IDDM) and 26 healthy subjects (14 prepubertal).
669 8910817 Serum IGF-I and IGFBP-3 levels were assayed using immunoradiometric assays and radioimmunoassays, respectively.
670 8910817 Serum IGF-I and IGFBP-3 levels in diabetics did not increase during puberty, as opposed to those in healthy children.
671 8910817 Serum IGF-I and IGFBP-3 levels of diabetic patients were found to be lower than those of control subjects during puberty (p < 0.0001 and p < 0.05, respectively).
672 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.
673 8910817 Our data displaying low IGFBP-3 levels in diabetic children may be due to increased proteolysis, which also causes a shift in IGF-I to its lower molecular weight forms.
674 8910817 The moderate correlation between insulin dose and IGFBP-3 levels (r = 0.5, p < 0.01) may suggest insulin to be a contributing factor in the regulation of IGFBP-3 levels.
675 8910817 We conclude that regulation of IGF-I and IGFBP-3 concentrations is disturbed in children with IDDM, in particular during adolescence.
676 8954066 Insulin like growth factor-binding protein-1 as a marker for hyperinsulinemia in obese menopausal women.
677 8954066 Insulin-like growth factor binding protein-1 (IGFBP-1), which had been shown previously to correlate inversely with insulin in animal and human studies, was evaluated as a diagnostic marker for abnormal glucose stimulated area under the curve (AUC) insulin (defined a priori as > or = 100 microU/ml).
678 8954066 We performed analysis of variance and logistic regression to assess IGFBP-1 and other study covariates, including body mass index, blood pressure, lipids and measures of glucose and insulin in hyperinsulinemic vs. normal women and evaluated performance characteristics (sensitivity, specificity, positive and negative predictive values and accuracy rates).
679 8954066 At a cutoff point of 15ng/ml, which was selected to correspond to the lower 95% confidence limit for the normal study population, IGFBP-1 was abnormal in all 13 women with hyperinsulinemia and 4 women with normal insulin levels (sensitivity 100%, specificity 69%; positive predictive value 76%, negative predictive value 100%, diagnostic accuracy rate 85%).
680 8954066 Logistic regression models indicated that, of all study covariates, IGFBP-1 was the best predictor variable for AUC-insulin as a binary dependent variable.
681 8954066 Insulin like growth factor-binding protein-1 as a marker for hyperinsulinemia in obese menopausal women.
682 8954066 Insulin-like growth factor binding protein-1 (IGFBP-1), which had been shown previously to correlate inversely with insulin in animal and human studies, was evaluated as a diagnostic marker for abnormal glucose stimulated area under the curve (AUC) insulin (defined a priori as > or = 100 microU/ml).
683 8954066 We performed analysis of variance and logistic regression to assess IGFBP-1 and other study covariates, including body mass index, blood pressure, lipids and measures of glucose and insulin in hyperinsulinemic vs. normal women and evaluated performance characteristics (sensitivity, specificity, positive and negative predictive values and accuracy rates).
684 8954066 At a cutoff point of 15ng/ml, which was selected to correspond to the lower 95% confidence limit for the normal study population, IGFBP-1 was abnormal in all 13 women with hyperinsulinemia and 4 women with normal insulin levels (sensitivity 100%, specificity 69%; positive predictive value 76%, negative predictive value 100%, diagnostic accuracy rate 85%).
685 8954066 Logistic regression models indicated that, of all study covariates, IGFBP-1 was the best predictor variable for AUC-insulin as a binary dependent variable.
686 8960832 Effect of intraperitoneal insulin delivery on growth hormone binding protein, insulin-like growth factor (IGF)-I, and IGF-binding protein-3 in IDDM.
687 8960832 Low plasma insulin-like growth factor (IGF)-I despite high circulating growth hormone (GH) in insulin-dependent diabetes mellitus (IDDM) indicate a hepatic GH resistance.
688 8960832 This state may be reflected by the reduction of the circulating GH binding protein (GHBP), corresponding to the extracellular domain of the GH receptor, and the reduction of insulin-like growth factor binding protein (IGFBP)-3, major IGF-I binding protein, upregulated by GH.
689 8960832 In the first, plasma GHBP activity was compared in patients with IDDM on continuous subcutaneous insulin infusion (CSII) or on conventional therapy and in healthy subjects.
690 8960832 CPII for 12 months resulted in: a slight and transient improvement in HbA1c (Time (T)0: 7.6 +/- 0.2%, T3: 7.1 +/- 0.2%, T12: 7.5 +/- 0.2%, p < 0.02), improvement in GHBP (T0: 10.2 +/- 0.8%, T12: 15.5 +/- 1.5, p < 0.0001), near-normalization of IGF-I (T0: 89.4 +/- 8.8 ng/ml, T12: 146.9 +/- 15.6, p < 0.002) and normalization of IGFBP-3 (T0: 1974 +/- 121 ng/ml, T12: 3534 +/- 305, p < 0.0001).
691 8960832 Intraperitoneal insulin delivery, allowing primary portal venous absorption, may influence GH sensitivity, and improve hepatic IGF-I and IGFBP-3 generation.
692 9014852 Maternal diabetes induces upregulation of hepatic insulin-like growth factor binding protein-1 MRNA expression, growth retardation and developmental delay at the same stage of rat fetal development.
693 9014852 Increased expression of Insulin-Like Growth Factor Binding Protein-I (IGFBP-1) is associated with several examples of growth retardation and is upregulated in response to diabetes.
694 9014852 Maternal diabetes induces upregulation of hepatic insulin-like growth factor binding protein-1 MRNA expression, growth retardation and developmental delay at the same stage of rat fetal development.
695 9014852 Increased expression of Insulin-Like Growth Factor Binding Protein-I (IGFBP-1) is associated with several examples of growth retardation and is upregulated in response to diabetes.
696 9030565 Identification of an insulin-responsive element in the rat insulin-like growth factor-binding protein-3 gene.
697 9030565 The hepatic expression and serum levels of insulin-like growth factor-binding protein-3 (IGFBP-3) are decreased in insulin-dependent and insulin-resistant diabetes.
698 9030565 Insulin increases hepatic IGFBP-3 expression by enhancing gene transcription.
699 9030565 This report identifies sequences within the IGFBP-3 promoter that are necessary and sufficient for the response to insulin in hepatic nonparenchymal cells.
700 9030565 By transient transfection, we mapped the insulin response element to the -1150 to -1124 base pair (bp) region of the rat IGFBP-3 promoter.
701 9030565 Thus, we have identified cis-acting DNA sequences that are responsible for regulation of IGFBP-3 transcription by insulin and essential for binding of insulin-responsive nuclear factors.
702 9030565 Identification of an insulin-responsive element in the rat insulin-like growth factor-binding protein-3 gene.
703 9030565 The hepatic expression and serum levels of insulin-like growth factor-binding protein-3 (IGFBP-3) are decreased in insulin-dependent and insulin-resistant diabetes.
704 9030565 Insulin increases hepatic IGFBP-3 expression by enhancing gene transcription.
705 9030565 This report identifies sequences within the IGFBP-3 promoter that are necessary and sufficient for the response to insulin in hepatic nonparenchymal cells.
706 9030565 By transient transfection, we mapped the insulin response element to the -1150 to -1124 base pair (bp) region of the rat IGFBP-3 promoter.
707 9030565 Thus, we have identified cis-acting DNA sequences that are responsible for regulation of IGFBP-3 transcription by insulin and essential for binding of insulin-responsive nuclear factors.
708 9032395 The Rep proteins of adeno-associated virus type 2 (AAV) are known to bind to Rep recognition sequences (RRSs) in the AAV inverted terminal repeats (ITRs), the AAV p5 promoter, and the preferred AAV integration site in human chromosome 19, called AAVS1.
709 9032395 We used the 16-mer core sequences of the RRSs in the AAV ITRs and AAVS1 separately as query sequences and identified 18 new RRSs in or flanking the genes coding for the following: tyrosine kinase activator protein 1 (TKA-1); colony stimulating factor-1; insulin-like growth factor binding protein 2 (IGFBP-2); histone H2B.1; basement membrane heparan sulfate proteoglycan, also known as perlecan; the AF-9 gene product, which is involved in the chromosomal translocation t (9:11)(p22:q23); the betaB subunit of the hormone known as inhibin; interleukin-2 enhancer binding factor; an endoplasmic reticulum-Golgi intermediate compartment resident protein called p63; a global transcription activator (hSNF2L); the beta-actin repair domain; a retinoic acid-inducible factor, also known as midkine; a breast tumor autoantigen; a growth-arrest- and DNA-damage-inducible protein called gadd45; the cyclin-dependent kinase inhibitor called KIP2, which inhibits several G1 cyclin-cyclin-dependent kinase complexes; and the hereditary breast and ovarian cancer gene (BRCA1).
710 9050949 Growth hormone binding proteins, insulin-like growth factor I and insulin-like growth factor binding proteins were determined in 54 children and adolescents affected by type 1 diabetes mellitus (25 prepubertal and 29 pubertal) showing reduced height velocity and the results were compared to those of 104 matched controls.
711 9050949 Insulin-like growth factor I was low both in prepubertal and pubertal diabetic subjects.
712 9050949 Insulin-like growth factor binding protein 3 was similar to controls, while insulin-like growth factor binding protein 1 and 2 were always high in diabetic children.
713 9050949 Insulin-like growth factor binding protein 4 was high only in the prepubertal diabetic group.
714 9050949 In conclusion, a low insulin-like growth factor I in diabetic children seems to depend on a GH receptor and/or a postreceptor defect.
715 9050949 A low insulin-like growth factor I together with a normal insulin-like growth factor binding protein 3 and high levels of insulin-like growth factor binding proteins 1, 2 and 4 results in a reduced bioavailability of insulin-like growth factor I to target tissues.
716 9050949 Growth hormone binding proteins, insulin-like growth factor I and insulin-like growth factor binding proteins were determined in 54 children and adolescents affected by type 1 diabetes mellitus (25 prepubertal and 29 pubertal) showing reduced height velocity and the results were compared to those of 104 matched controls.
717 9050949 Insulin-like growth factor I was low both in prepubertal and pubertal diabetic subjects.
718 9050949 Insulin-like growth factor binding protein 3 was similar to controls, while insulin-like growth factor binding protein 1 and 2 were always high in diabetic children.
719 9050949 Insulin-like growth factor binding protein 4 was high only in the prepubertal diabetic group.
720 9050949 In conclusion, a low insulin-like growth factor I in diabetic children seems to depend on a GH receptor and/or a postreceptor defect.
721 9050949 A low insulin-like growth factor I together with a normal insulin-like growth factor binding protein 3 and high levels of insulin-like growth factor binding proteins 1, 2 and 4 results in a reduced bioavailability of insulin-like growth factor I to target tissues.
722 9050949 Growth hormone binding proteins, insulin-like growth factor I and insulin-like growth factor binding proteins were determined in 54 children and adolescents affected by type 1 diabetes mellitus (25 prepubertal and 29 pubertal) showing reduced height velocity and the results were compared to those of 104 matched controls.
723 9050949 Insulin-like growth factor I was low both in prepubertal and pubertal diabetic subjects.
724 9050949 Insulin-like growth factor binding protein 3 was similar to controls, while insulin-like growth factor binding protein 1 and 2 were always high in diabetic children.
725 9050949 Insulin-like growth factor binding protein 4 was high only in the prepubertal diabetic group.
726 9050949 In conclusion, a low insulin-like growth factor I in diabetic children seems to depend on a GH receptor and/or a postreceptor defect.
727 9050949 A low insulin-like growth factor I together with a normal insulin-like growth factor binding protein 3 and high levels of insulin-like growth factor binding proteins 1, 2 and 4 results in a reduced bioavailability of insulin-like growth factor I to target tissues.
728 9075727 Insulin-like growth factor-I (IGF-I) concentration in 150-kilodalton complexes containing human IGF-binding protein-3 (hIGFBP-3) after intravenous injection of adult rats with hIGFBP-3.
729 9075727 After i.v. injection into adult rats, human insulin-like growth factor-binding protein-3 (hIGFBP-3) forms 150-kDa complexes with excess endogenous rat acid-labile subunit (ALS) within 2 min (Lewitt et al., 1993, Endocrinology 133:1797).
730 9075727 Because their previous in vitro studies indicated that hIGFBP-3 only bound to ALS in the presence of IGF-I, and because little free IGF-I is present in plasma, the authors postulated that IGF-I had been mobilized to the circulation to saturate the 150-kDa hIGFBP-3 complexes.
731 9075727 Gel filtration and immunoprecipitation studies performed on blood collected 2 min after injection confirmed that the injected hIGFBP-3 (46-82% as much as rat IGFBP-3) was associated with ALS in 150-kDa complexes.
732 9075727 Insulin-like growth factor-I (IGF-I) concentration in 150-kilodalton complexes containing human IGF-binding protein-3 (hIGFBP-3) after intravenous injection of adult rats with hIGFBP-3.
733 9075727 After i.v. injection into adult rats, human insulin-like growth factor-binding protein-3 (hIGFBP-3) forms 150-kDa complexes with excess endogenous rat acid-labile subunit (ALS) within 2 min (Lewitt et al., 1993, Endocrinology 133:1797).
734 9075727 Because their previous in vitro studies indicated that hIGFBP-3 only bound to ALS in the presence of IGF-I, and because little free IGF-I is present in plasma, the authors postulated that IGF-I had been mobilized to the circulation to saturate the 150-kDa hIGFBP-3 complexes.
735 9075727 Gel filtration and immunoprecipitation studies performed on blood collected 2 min after injection confirmed that the injected hIGFBP-3 (46-82% as much as rat IGFBP-3) was associated with ALS in 150-kDa complexes.
736 9075727 Insulin-like growth factor-I (IGF-I) concentration in 150-kilodalton complexes containing human IGF-binding protein-3 (hIGFBP-3) after intravenous injection of adult rats with hIGFBP-3.
737 9075727 After i.v. injection into adult rats, human insulin-like growth factor-binding protein-3 (hIGFBP-3) forms 150-kDa complexes with excess endogenous rat acid-labile subunit (ALS) within 2 min (Lewitt et al., 1993, Endocrinology 133:1797).
738 9075727 Because their previous in vitro studies indicated that hIGFBP-3 only bound to ALS in the presence of IGF-I, and because little free IGF-I is present in plasma, the authors postulated that IGF-I had been mobilized to the circulation to saturate the 150-kDa hIGFBP-3 complexes.
739 9075727 Gel filtration and immunoprecipitation studies performed on blood collected 2 min after injection confirmed that the injected hIGFBP-3 (46-82% as much as rat IGFBP-3) was associated with ALS in 150-kDa complexes.
740 9080393 Characterization of IGFBP-3, PAI-1 and SPARC mRNA expression in senescent fibroblasts.
741 9080393 The RNA species encoded by IGFBP-3 (insulin-like growth factor binding protein-3), PAI-1 (plasminogen activator inhibitor-1) and SPARC (secreted protein-acidic and rich in cysteine; a.k.a. osteonectin) are overexpressed in senescent human diploid fibroblasts (HDF).
742 9080393 Characterization of the rates of transcription and the levels of message stability of these genes in early passage (young) versus late passage (old) HDF revealed that IGFBP-3, PAI-1 and SPARC are coordinately overexpressed but not regulated by a unique or simple mechanism encompassing all three transcripts.
743 9112407 Insulin-like growth factor binding protein-1 induces insulin release in the rat.
744 9112407 Injections of human insulin-like growth factor binding protein (hIGFBP-1) are reported to induce hyperglycemia in the rat, suggesting that IGFBP-1 acutely regulates glucose homeostasis.
745 9112407 We now report the effects on glucose and insulin levels of administering recombinant (r) hIGFBP-1.
746 9112407 In a series of studies, normal and streptozotocin (STZ) diabetic male Wistar rats (180-210 g), fasted for 6 or 16 h, were injected with rhIGFBP-1 (i.v., 80-500 microg/rat). rhIGFBP-1 did not affect blood glucose acutely but did stimulate insulin release in normal rats (5 min post injection; PBS, 103.5 +/- 8.5; rhIGFBP-1 (500 microg), 166.8 +/- 15.7; rhIGFBP-1 (100 microg); 151.4 +/- 14.1% initial). rhIGFBP-1 pretreatment, in normal and diabetic rats, reduced the hypoglycemic response to rhIGF-I (diabetic rats after 20 min: PBS, 103.4 +/- 11.4; BP-1 (500 microg) +/- rhIGF-I (50 microg), 97.6 +/- 3.6; rhIGF-I, 48.2 +/- 4.3% initial) but did not affect the hypoglycemic response to des(1-3)IGF-I or insulin (0.5 U/kg).
747 9112407 These data suggest that endogenous IGF-I tonically suppresses insulin secretion and imply that aberrant IGFBP levels or reduced IGF-I bioactivity may lead to chronic hyperinsulinemia.
748 9112407 Insulin-like growth factor binding protein-1 induces insulin release in the rat.
749 9112407 Injections of human insulin-like growth factor binding protein (hIGFBP-1) are reported to induce hyperglycemia in the rat, suggesting that IGFBP-1 acutely regulates glucose homeostasis.
750 9112407 We now report the effects on glucose and insulin levels of administering recombinant (r) hIGFBP-1.
751 9112407 In a series of studies, normal and streptozotocin (STZ) diabetic male Wistar rats (180-210 g), fasted for 6 or 16 h, were injected with rhIGFBP-1 (i.v., 80-500 microg/rat). rhIGFBP-1 did not affect blood glucose acutely but did stimulate insulin release in normal rats (5 min post injection; PBS, 103.5 +/- 8.5; rhIGFBP-1 (500 microg), 166.8 +/- 15.7; rhIGFBP-1 (100 microg); 151.4 +/- 14.1% initial). rhIGFBP-1 pretreatment, in normal and diabetic rats, reduced the hypoglycemic response to rhIGF-I (diabetic rats after 20 min: PBS, 103.4 +/- 11.4; BP-1 (500 microg) +/- rhIGF-I (50 microg), 97.6 +/- 3.6; rhIGF-I, 48.2 +/- 4.3% initial) but did not affect the hypoglycemic response to des(1-3)IGF-I or insulin (0.5 U/kg).
752 9112407 These data suggest that endogenous IGF-I tonically suppresses insulin secretion and imply that aberrant IGFBP levels or reduced IGF-I bioactivity may lead to chronic hyperinsulinemia.
753 9121490 Dexamethasone stimulation of rat insulin-like growth factor binding protein-1 promoter activity involves multiple cis-elements.
754 9121490 Insulin-like growth factor binding protein-1 (IGFBP-1) modulates the mitogenic actions of IGF-I and IGF-II.
755 9121490 Dexamethasone stimulation of rat insulin-like growth factor binding protein-1 promoter activity involves multiple cis-elements.
756 9121490 Insulin-like growth factor binding protein-1 (IGFBP-1) modulates the mitogenic actions of IGF-I and IGF-II.
757 9178759 Growth hormone stimulates transcription of the gene encoding the acid-labile subunit (ALS) of the circulating insulin-like growth factor-binding protein complex and ALS promoter activity in rat liver.
758 9178759 The growth-promoting activity of GH, the principal hormonal determinant of body size, is mediated by insulin-like growth factor I (IGF-I).
759 9178759 Most of the IGF-I in plasma circulates in a 150-kDa complex that contains IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit (ALS).
760 9178759 Growth hormone stimulates transcription of the gene encoding the acid-labile subunit (ALS) of the circulating insulin-like growth factor-binding protein complex and ALS promoter activity in rat liver.
761 9178759 The growth-promoting activity of GH, the principal hormonal determinant of body size, is mediated by insulin-like growth factor I (IGF-I).
762 9178759 Most of the IGF-I in plasma circulates in a 150-kDa complex that contains IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit (ALS).
763 9202228 Bovine insulin-like growth factor binding protein-3: organization of the chromosomal gene and functional analysis of its promoter.
764 9202228 Insulin-like growth factor binding protein-3 (IGFBP-3), the major IGFBP in the circulation, is synthesized by the vascular endothelium in vivo and has been shown to be an important modulator of the physiological effects of IGF.
765 9202228 IGFBP-3 is regulated by a number of growth factors/cytokines to which the vascular endothelium is exposed, including IGF-I stimulation and TGF-beta1 inhibition of IGFBP-3 in cultured endothelial cells.
766 9202228 Results of the transfection studies indicated that 1) nearly 80% of the maximal basal promoter activity was retained within the first 130 bp of the 5' flanking sequence; 2) this region responded to IGF-I, despite lacking the TTF-1/TTF-2 (thyroid specific transcription factors) binding elements that are required for IGF-I stimulation of thyroglobulin synthesis.
767 9202228 These binding elements have also been suggested to be involved in IGF-I regulation of IGFBP-3 transcription, thus, implying the existence of novel cis-acting elements that mediate the IGF-I stimulation of bovine endothelial cell IGFBP-3 mRNA synthesis; 3) deletion of the GC rich sequence element resulted in a 60% reduction in basal promoter activity as well as loss of the IGF-1 stimulatory effect; 4) the TGF-beta1 mediated inhibition of IGFBP-3 transcription required sequence element(s) beyond 1.5 kb of its promoter.
768 9202228 Bovine insulin-like growth factor binding protein-3: organization of the chromosomal gene and functional analysis of its promoter.
769 9202228 Insulin-like growth factor binding protein-3 (IGFBP-3), the major IGFBP in the circulation, is synthesized by the vascular endothelium in vivo and has been shown to be an important modulator of the physiological effects of IGF.
770 9202228 IGFBP-3 is regulated by a number of growth factors/cytokines to which the vascular endothelium is exposed, including IGF-I stimulation and TGF-beta1 inhibition of IGFBP-3 in cultured endothelial cells.
771 9202228 Results of the transfection studies indicated that 1) nearly 80% of the maximal basal promoter activity was retained within the first 130 bp of the 5' flanking sequence; 2) this region responded to IGF-I, despite lacking the TTF-1/TTF-2 (thyroid specific transcription factors) binding elements that are required for IGF-I stimulation of thyroglobulin synthesis.
772 9202228 These binding elements have also been suggested to be involved in IGF-I regulation of IGFBP-3 transcription, thus, implying the existence of novel cis-acting elements that mediate the IGF-I stimulation of bovine endothelial cell IGFBP-3 mRNA synthesis; 3) deletion of the GC rich sequence element resulted in a 60% reduction in basal promoter activity as well as loss of the IGF-1 stimulatory effect; 4) the TGF-beta1 mediated inhibition of IGFBP-3 transcription required sequence element(s) beyond 1.5 kb of its promoter.
773 9246719 Insulin-like growth factor-I (IGF-I) is a pleiotropic protein that acts on many tissues and organs.
774 9246719 Most recently, a clinical trial has revealed the beneficial effects of IGF-I in amyotrophic lateral-sclerosis (ALS), a degenerative disease of the motoneurones.
775 9246719 We review briefly here experimental and clinical information that suggests the potential usefulness of IGF-I in the treatment of certain neurodegenerative diseases, including ALS, Alzheimer's disease, various neuropathies and brain trauma.
776 9246719 Insulin-like growth factor-I (IGF-I) is a pleiotropic protein that acts on many tissues and organs.
777 9246719 Most recently, a clinical trial has revealed the beneficial effects of IGF-I in amyotrophic lateral-sclerosis (ALS), a degenerative disease of the motoneurones.
778 9246719 We review briefly here experimental and clinical information that suggests the potential usefulness of IGF-I in the treatment of certain neurodegenerative diseases, including ALS, Alzheimer's disease, various neuropathies and brain trauma.
779 9369450 Hepatocyte nuclear factor 1 and the glucocorticoid receptor synergistically activate transcription of the rat insulin-like growth factor binding protein-1 gene.
780 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.
781 9369450 In gel shift assays, HNF-1alpha and HNF-1beta in H4-II-E extracts bind to the palindromic HNF-1 site.
782 9369450 Thus, the synergistic effects of HNF-1beta and the GR on dexamethasone-stimulated promoter activity require that they are bound to the HNF-1 site and the GRE, respectively, and may involve protein-protein interactions between the transcription factors, or between them and the basal transcription machinery or a steroid receptor coactivator.
783 9421396 Effect of glucose on insulin-like growth factor binding protein-4 proteolysis.
784 9421396 The role of hyperglycemia in diabetic changes of the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) has not been clearly established.
785 9421396 The results suggest that high glucose acts on pSMC to induce a change in IGFBP-4 proteolytic activity, which results in increased IGF-I availability to its receptors thereby enhancing the SMC proliferative response.
786 9439529 Insulin-like growth factor binding protein production in bovine retinal endothelial cells.
787 9439529 Bovine retinal endothelial cells (BRECs) were cultured to investigate if insulin, insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and a chronic high-glucose condition could control endothelial cell growth.
788 9439529 Insulin, which does not bind to IGFBPs, was a potent mitogenic factor in these cells at a high concentration (10 nmol/L), suggesting a cross-reaction to IGF-I receptor.
789 9439529 These IGFBPs, except the 24-kd form (IGFBP-4), were modulated by both IGF-I and IGF-II, with a maximum effect at 100 and 10 nmol/L, respectively.
790 9439529 In fact, (1) IGFBP mRNA levels were not modified after stimulation with 100 nmol/L IGF-I, (2) 100 nmol/L IGF plus an equimolar concentration of alpha IR3 did not affect IGFBP production, (3) Des(1-3)IGF-I had no effect on IGFBP modulation, whereas at 10 nmol/L it enhanced BREC thymidine cell incorporation, and (4) 100 nmol/L insulin, which at this concentration can cross-react with the IGF-I receptor, did not modify the IGFBP pattern.
791 9439529 In conclusion, we showed that conditions mimicking hyperinsulinemia, rather than high levels of IGFs, could regulate BREC growth and that the IGF-I analog, Des(1-3), even with reduced affinity for IGFBPs but in part capable of binding to IGFBP-3, significantly stimulated BRECs growth only at 10 nmol/L.
792 9449038 Over the last several years, the authors have studied the relationship of insulin-like growth factors (IGFs) and the insulin-like growth factor binding proteins (IGFBPs) in the circulation in a number of clinical settings.
793 9449038 In aging, there are marked decreases in IGF-I and -II, normal levels of IGFBP-3, and marked increases in IGFBP-1 in serum.
794 9449038 In these conditions, serum levels of IGF-I and -II are markedly diminished, IGFBP-3 levels are also decreased, and IGFBP-1 levels are markedly increased.
795 9449038 In addition, there is increased proteolysis of IGFBP-3 (AIDS failure to thrive, uncontrolled diabetes mellitus) and disruption of the ternary complex with decreased levels of ALS (AIDS wasting and burns).
796 9604870 Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats.
797 9604870 The early renal growth in streptozotocin (STZ)-induced diabetic rats is preceded by a transient rise in renal tissue insulin-like growth factor (IGF)-I concentration.
798 9604870 Administration of the long-acting somatostatin analog octreotide to STZ diabetic rats inhibits the early increase in kidney IGF-I and the increase in kidney size without affecting metabolic control.
799 9604870 Renal IGF-I mRNA was significantly decreased to the same extent in both diabetic groups 2 and 7 days after the induction of diabetes, while renal IGF-I receptor (IGF-IR) mRNA was unchanged in rats from either group.
800 9604870 Two days after induction of diabetes, renal insulin-like growth factor binding protein (IGFBP)-1 mRNA and 30-kDa IGFBPs (containing IGFBP-1) increased by 186 and 192%, respectively, in untreated diabetic animals compared with controls.
801 9604870 We conclude that the well-known inhibitory effect of octreotide on the early increase in renal IGF-I concentration and renal size in diabetes may be mediated through a direct effect on renal IGFBP-1 levels.
802 9604870 Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats.
803 9604870 The early renal growth in streptozotocin (STZ)-induced diabetic rats is preceded by a transient rise in renal tissue insulin-like growth factor (IGF)-I concentration.
804 9604870 Administration of the long-acting somatostatin analog octreotide to STZ diabetic rats inhibits the early increase in kidney IGF-I and the increase in kidney size without affecting metabolic control.
805 9604870 Renal IGF-I mRNA was significantly decreased to the same extent in both diabetic groups 2 and 7 days after the induction of diabetes, while renal IGF-I receptor (IGF-IR) mRNA was unchanged in rats from either group.
806 9604870 Two days after induction of diabetes, renal insulin-like growth factor binding protein (IGFBP)-1 mRNA and 30-kDa IGFBPs (containing IGFBP-1) increased by 186 and 192%, respectively, in untreated diabetic animals compared with controls.
807 9604870 We conclude that the well-known inhibitory effect of octreotide on the early increase in renal IGF-I concentration and renal size in diabetes may be mediated through a direct effect on renal IGFBP-1 levels.
808 9605930 Binding of STAT5a and STAT5b to a single element resembling a gamma-interferon-activated sequence mediates the growth hormone induction of the mouse acid-labile subunit promoter in liver cells.
809 9605930 After birth, the endocrine actions of insulin-like growth factor (IGF)-I and -II become increasingly important.
810 9605930 In postnatal animals, most of circulating IGFs occur in 150-kDa complexes formed by association of an acid-labile subunit (ALS) with complexes of IGF and IGF-binding protein-3.
811 9605930 To map the GH response element, a series of 5'-deletion fragments of the mouse ALS promoter (nt -2001 to -49, A(+1)TG) were inserted in the luciferase reporter plasmid pGL3 and transfected into the H4-II-E rat hepatoma cell line.
812 9605930 Using antibodies directed against members of the family of signal transducers and activators of transcription (STAT), this complex was shown to be composed of STAT5a and STAT5b.
813 9605930 Thus, the transcriptional activation of the mouse ALS gene by GH is mediated by the binding of STAT5 isoforms to a single GAS-like element.
814 9605930 Binding of STAT5a and STAT5b to a single element resembling a gamma-interferon-activated sequence mediates the growth hormone induction of the mouse acid-labile subunit promoter in liver cells.
815 9605930 After birth, the endocrine actions of insulin-like growth factor (IGF)-I and -II become increasingly important.
816 9605930 In postnatal animals, most of circulating IGFs occur in 150-kDa complexes formed by association of an acid-labile subunit (ALS) with complexes of IGF and IGF-binding protein-3.
817 9605930 To map the GH response element, a series of 5'-deletion fragments of the mouse ALS promoter (nt -2001 to -49, A(+1)TG) were inserted in the luciferase reporter plasmid pGL3 and transfected into the H4-II-E rat hepatoma cell line.
818 9605930 Using antibodies directed against members of the family of signal transducers and activators of transcription (STAT), this complex was shown to be composed of STAT5a and STAT5b.
819 9605930 Thus, the transcriptional activation of the mouse ALS gene by GH is mediated by the binding of STAT5 isoforms to a single GAS-like element.
820 9605930 Binding of STAT5a and STAT5b to a single element resembling a gamma-interferon-activated sequence mediates the growth hormone induction of the mouse acid-labile subunit promoter in liver cells.
821 9605930 After birth, the endocrine actions of insulin-like growth factor (IGF)-I and -II become increasingly important.
822 9605930 In postnatal animals, most of circulating IGFs occur in 150-kDa complexes formed by association of an acid-labile subunit (ALS) with complexes of IGF and IGF-binding protein-3.
823 9605930 To map the GH response element, a series of 5'-deletion fragments of the mouse ALS promoter (nt -2001 to -49, A(+1)TG) were inserted in the luciferase reporter plasmid pGL3 and transfected into the H4-II-E rat hepatoma cell line.
824 9605930 Using antibodies directed against members of the family of signal transducers and activators of transcription (STAT), this complex was shown to be composed of STAT5a and STAT5b.
825 9605930 Thus, the transcriptional activation of the mouse ALS gene by GH is mediated by the binding of STAT5 isoforms to a single GAS-like element.
826 9615225 Structure and transcription regulation of the human insulin-like growth factor binding protein 4 gene (IGFBP4).
827 9615225 Insulin-like growth factor binding protein 4 (IGFBP-4) is locally produced by normal human bone cells and acts as a potent inhibitor of IGF action in this tissue.
828 9615225 Structure and transcription regulation of the human insulin-like growth factor binding protein 4 gene (IGFBP4).
829 9615225 Insulin-like growth factor binding protein 4 (IGFBP-4) is locally produced by normal human bone cells and acts as a potent inhibitor of IGF action in this tissue.
830 9628244 Insulin-like growth factor binding protein-3 levels during early and late follow-up after surgery in acromegalic patients.
831 9628244 Disease activity in acromegaly is accurately reflected by growth hormone (GH) concentration during oral glucose tolerance test (OGTT) and insulin-like growth factor-I (IGF-I) levels, representing an integrated index of GH activity.
832 9628244 The hormonal assessment included repeated blood samples for estimation of IGF-I, IGFBP-3 and repeated OGTTs.
833 9628244 In each case 100 sigma g octreotide (Sandostatin lambda, Sandoz, Basel) was injected to test the acute response of GH, IGF-I and IGFBP-3.
834 9628244 Despite these observations a strong correlation of IGF-I and IGFBP-3 did not exist before one year post-operatively -- either in the cured or in the non-cured patients.
835 9661636 Postoperative induction of insulin-like growth factor binding protein-3 proteolytic activity: relation to insulin and insulin sensitivity.
836 9661636 Increased serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) proteolytic activity (IGFBP-3-PA) has been demonstrated in a number of clinical states of insulin resistance, including severe illness, after surgery, and in noninsulin-dependent diabetes mellitus.
837 9661636 Characterization of the IGFBP-3-PA demonstrated that it was specific for IGFBP-3, as no degradation of IGFBP-1 and -2 was detected, and the use of various protease inhibitors demonstrated that serine proteases and possibly matrix metalloproteinases contribute to the increased IGFBP-3-PA level after surgery.
838 9709957 Identification of novel high molecular weight insulin-like growth factor-binding protein-3 association proteins in human serum.
839 9709957 The insulin-like growth factor (IGF)-binding proteins (IGFBPs) carry IGFs in serum and regulate their activity and bioavailability.
840 9709957 The main IGFBP in serum, IGFBP-3, is known to form a 150-kDa complex with IGFs and the acid-labile subunit (ALS).
841 9709957 Serum ALS migrated separately (at 88 kDa) from the novel IGFBP-3 APs (as evident by Western immunoblot), and bound IGFBP-3 weakly (by reverse ligand blots).
842 9709957 We also demonstrated that large amounts of one of the IGFBP-3 APs and small amounts of ALS were coimmunoprecipitated with IGFBP-3 from human serum.
843 9709957 Similar to ALS, these IGFBP-3 APs are acid labile and lose their IGFBP-3 binding capacity after exposure to low pH.
844 9709957 We conclude that there are several serum proteins in addition to ALS and IGFs that bind IGFBP-3 with high affinity.
845 9709957 Identification of novel high molecular weight insulin-like growth factor-binding protein-3 association proteins in human serum.
846 9709957 The insulin-like growth factor (IGF)-binding proteins (IGFBPs) carry IGFs in serum and regulate their activity and bioavailability.
847 9709957 The main IGFBP in serum, IGFBP-3, is known to form a 150-kDa complex with IGFs and the acid-labile subunit (ALS).
848 9709957 Serum ALS migrated separately (at 88 kDa) from the novel IGFBP-3 APs (as evident by Western immunoblot), and bound IGFBP-3 weakly (by reverse ligand blots).
849 9709957 We also demonstrated that large amounts of one of the IGFBP-3 APs and small amounts of ALS were coimmunoprecipitated with IGFBP-3 from human serum.
850 9709957 Similar to ALS, these IGFBP-3 APs are acid labile and lose their IGFBP-3 binding capacity after exposure to low pH.
851 9709957 We conclude that there are several serum proteins in addition to ALS and IGFs that bind IGFBP-3 with high affinity.
852 9709957 Identification of novel high molecular weight insulin-like growth factor-binding protein-3 association proteins in human serum.
853 9709957 The insulin-like growth factor (IGF)-binding proteins (IGFBPs) carry IGFs in serum and regulate their activity and bioavailability.
854 9709957 The main IGFBP in serum, IGFBP-3, is known to form a 150-kDa complex with IGFs and the acid-labile subunit (ALS).
855 9709957 Serum ALS migrated separately (at 88 kDa) from the novel IGFBP-3 APs (as evident by Western immunoblot), and bound IGFBP-3 weakly (by reverse ligand blots).
856 9709957 We also demonstrated that large amounts of one of the IGFBP-3 APs and small amounts of ALS were coimmunoprecipitated with IGFBP-3 from human serum.
857 9709957 Similar to ALS, these IGFBP-3 APs are acid labile and lose their IGFBP-3 binding capacity after exposure to low pH.
858 9709957 We conclude that there are several serum proteins in addition to ALS and IGFs that bind IGFBP-3 with high affinity.
859 9709957 Identification of novel high molecular weight insulin-like growth factor-binding protein-3 association proteins in human serum.
860 9709957 The insulin-like growth factor (IGF)-binding proteins (IGFBPs) carry IGFs in serum and regulate their activity and bioavailability.
861 9709957 The main IGFBP in serum, IGFBP-3, is known to form a 150-kDa complex with IGFs and the acid-labile subunit (ALS).
862 9709957 Serum ALS migrated separately (at 88 kDa) from the novel IGFBP-3 APs (as evident by Western immunoblot), and bound IGFBP-3 weakly (by reverse ligand blots).
863 9709957 We also demonstrated that large amounts of one of the IGFBP-3 APs and small amounts of ALS were coimmunoprecipitated with IGFBP-3 from human serum.
864 9709957 Similar to ALS, these IGFBP-3 APs are acid labile and lose their IGFBP-3 binding capacity after exposure to low pH.
865 9709957 We conclude that there are several serum proteins in addition to ALS and IGFs that bind IGFBP-3 with high affinity.
866 9709957 Identification of novel high molecular weight insulin-like growth factor-binding protein-3 association proteins in human serum.
867 9709957 The insulin-like growth factor (IGF)-binding proteins (IGFBPs) carry IGFs in serum and regulate their activity and bioavailability.
868 9709957 The main IGFBP in serum, IGFBP-3, is known to form a 150-kDa complex with IGFs and the acid-labile subunit (ALS).
869 9709957 Serum ALS migrated separately (at 88 kDa) from the novel IGFBP-3 APs (as evident by Western immunoblot), and bound IGFBP-3 weakly (by reverse ligand blots).
870 9709957 We also demonstrated that large amounts of one of the IGFBP-3 APs and small amounts of ALS were coimmunoprecipitated with IGFBP-3 from human serum.
871 9709957 Similar to ALS, these IGFBP-3 APs are acid labile and lose their IGFBP-3 binding capacity after exposure to low pH.
872 9709957 We conclude that there are several serum proteins in addition to ALS and IGFs that bind IGFBP-3 with high affinity.
873 9709957 Identification of novel high molecular weight insulin-like growth factor-binding protein-3 association proteins in human serum.
874 9709957 The insulin-like growth factor (IGF)-binding proteins (IGFBPs) carry IGFs in serum and regulate their activity and bioavailability.
875 9709957 The main IGFBP in serum, IGFBP-3, is known to form a 150-kDa complex with IGFs and the acid-labile subunit (ALS).
876 9709957 Serum ALS migrated separately (at 88 kDa) from the novel IGFBP-3 APs (as evident by Western immunoblot), and bound IGFBP-3 weakly (by reverse ligand blots).
877 9709957 We also demonstrated that large amounts of one of the IGFBP-3 APs and small amounts of ALS were coimmunoprecipitated with IGFBP-3 from human serum.
878 9709957 Similar to ALS, these IGFBP-3 APs are acid labile and lose their IGFBP-3 binding capacity after exposure to low pH.
879 9709957 We conclude that there are several serum proteins in addition to ALS and IGFs that bind IGFBP-3 with high affinity.
880 9741824 Insulin-like growth factor-I and insulin-like growth factor binding protein-1 in a representative population of type 2 diabetic patients in Sweden.
881 9747960 Relationship between non-enzymatic glycosylation and changes in serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels in patients with type 2 diabetes mellitus.
882 9747960 The possible occurrence of increased non-enzymatic glycosylation of serum insulin-like growth factor binding protein-3 (IGFBP-3) in vivo and the changes that would simultaneously occur in serum levels of IGFBP-3 and insulin-like growth factor-1 (IGF-I) were investigated.
883 9747960 We measured levels of IGF-I and IGFBP-3 and the degree of glycation of total serum protein and IGFBP-3, in serum samples obtained from patients with poorly controlled non-insulin-dependent diabetes (type 2) and from age-matched non-diabetic controls.
884 9747960 The IGF-I/IGFBP-3 molar ratio was significantly reduced in the 46-60-year-old type 2 diabetic group, whereas the IGF-I/IGFBP-3 ratio was positively and significantly correlated with GlyP levels only in the control group (r = 0.489, P<0.01).
885 9747960 These results suggest that the IGF-I/IGFBP-3 system is another target for the metabolic derangements of type 2 diabetes.
886 9765271 FATP mRNA levels are down-regulated by insulin in cultured 3T3-L1 adipocytes and up-regulated by nutrient depletion in murine adipose tissue (Man, M.
887 9765271 To determine the molecular mechanism of insulin regulation of FATP transcription, we have isolated the murine FATP gene and its 5'-flanking sequences.
888 9765271 By transient transfection assays in 3T3-L1 adipocytes, the inhibitory action of insulin on FATP transcription was localized to a cis-acting element with the sequence 5'-TGTTTTC-3' from -1347 to -1353.
889 9765271 This sequence is very similar to the insulin response sequence found in the regulatory region of other genes negatively regulated by insulin such as those encoding phosphoenolpyruvate carboxykinase, tyrosine aminotransferase, and insulin-like growth factor-binding protein 1.
890 9765271 Interestingly, this region of chromosome 8 contains a cluster of three other genes important for fatty acid homeostasis, lipoprotein lipase, the mitochondrial uncoupling protein 1 (UCP1) and sterol regulatory element-binding protein 1.
891 9765271 These results characterize the murine FATP gene and its insulin responsiveness as well as present a framework for future studies of its role in lipid metabolism, obesity, and type II diabetes mellitus.
892 9790247 Insulin-like growth factors - insulin-like growth factor binding protein axis and diabetic control in insulin-dependent diabetes mellitus.
893 9790247 There is some evidence that insulin-like growth factors (IGFs) and/or IGF binding proteins (IGFBPs) (IGF-IGFBP axis) may be involved in glucose metabolism.
894 9790247 The purpose of this study was to investigate the relationship between the IGF-IGFBP axis and diabetic control in subjects with insulin-dependent diabetes mellitus (IDDM).
895 9790247 In all subjects, the free form of IGF-I (free IGF-I), the total IGF-I (total IGF-I: free plus complexed form of IGF-I) and IGFBP-3 in serum or plasma were measured.
896 9790247 The Z-scores of free IGF-I, total IGF-I, and IGFBP-3 were calculated.
897 9790247 In 18 young adults with IDDM (age 18.0-30.3 years, 5 males and 13 females), IGFBP-1 in serum was also measured.
898 9790247 In all subjects, the diabetic control parameters such as blood glucose (BS) (momentary control), 1,5-anhydro-D-glucitol (1,5 AG) (Ultrashort-term), fructosamine (short term), and glycosylated hemoglobin (HbA1) (long-term) were measured.
899 9790247 None of the Z scores for free IGF-I, total IGF-I or IGFBP-3 had a significant correlation with BS.
900 9790247 None of the Z scores for free IGF-I, total IGF-I or IGFBP-3 had a significant correlation with 1,5 AG, fructosamine or HbA1.
901 9790247 In young adults, IGFBP-1 did not correlate with 1,5 AG, fructosamine or HbA1.
902 9795360 Serum insulin-like growth factor-binding protein-3 (IGFBP-3) assessed by ligand blot was also reduced in ZD rats (65% of PF; P<0. 01).
903 9795360 However, circulating IGF-I and IGFBP-3 levels were restored by IGF-I infusion to levels similar to those in untreated CTRL rats.
904 9795360 In conclusion, restoration of normal circulating levels of IGF-I and IGFBP-3 by rhIGF-I infusion fails to reverse the growth retardation induced by zinc deficiency.
905 9892227 The heightened hepatic insulin sensitivity is supported by the decrease in gene expression of both glucose-6-phosphatase and PEPCK and by physiological hyperinsulinemia in VF- but not VF+ rats.
906 9892227 The improvement in hepatic insulin sensitivity in VF- rats was also supported by a approximately 70% decrease in the plasma levels of insulin-like growth factor binding protein-1, a marker of insulin's transcription regulation in the liver.
907 9892227 The removal of VF pads also resulted in marked decreases in the gene expression of tumor necrosis factor-alpha (by 72%) and leptin (by 60%) in subcutaneous fat.
908 10070009 Insulin-like growth factor-binding protein-3 (IGFBP-3) was digested with plasmin, and the proteolytic fragments were isolated by HPLC and tested for bioactivity as measured by stimulation of glucose uptake in microvessel endothelial cells.
909 10070009 Both fragments bound 125I-labeled insulin-like growth factor and [3H]heparin.
910 10077006 Transcriptional and posttranscriptional regulation of insulin-like growth factor binding protein-3 by cyclic adenosine 3',5'-monophosphate: messenger RNA stabilization is accompanied by decreased binding of a 42-kDa protein to a uridine-rich domain in the 3'-untranslated region.
911 10077006 The Madin Darby bovine kidney (MDBK) cell line was used to investigate the mechanisms underlying the cAMP regulation of insulin-like growth factor binding protein-3 (IGFBP-3) gene expression.
912 10077006 Transcriptional and posttranscriptional regulation of insulin-like growth factor binding protein-3 by cyclic adenosine 3',5'-monophosphate: messenger RNA stabilization is accompanied by decreased binding of a 42-kDa protein to a uridine-rich domain in the 3'-untranslated region.
913 10077006 The Madin Darby bovine kidney (MDBK) cell line was used to investigate the mechanisms underlying the cAMP regulation of insulin-like growth factor binding protein-3 (IGFBP-3) gene expression.
914 10087296 Characterization and chromosomal localization of the human insulin-like growth factor-binding protein 6 gene.
915 10087296 Insulin-like growth factor-binding protein 6 (IGFBP6), an extracellular protein with preferential affinity for insulin-like growth factor (IGF) II, belongs to a family of binding proteins with at least six members.
916 10087296 Characterization and chromosomal localization of the human insulin-like growth factor-binding protein 6 gene.
917 10087296 Insulin-like growth factor-binding protein 6 (IGFBP6), an extracellular protein with preferential affinity for insulin-like growth factor (IGF) II, belongs to a family of binding proteins with at least six members.
918 10226800 The absence of 150-kDa insulin-like growth factor complexes in fetal rat serum is not due to a lack of functional acid-labile subunit.
919 10226800 Most of the insulin-like growth factors (IGFs) in adult rat or human plasma circulate in 150-kDa heterotrimeric complexes with IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit (ALS).
920 10226800 We report that ALS mRNA is expressed in term fetal rat liver at 30% of the levels in adult liver, that radioiodinated rat ALS is not proteolyzed by incubation with fetal rat serum, and that sufficient functional ALS is present in fetal rat serum to form 150-kDa complexes with recombinant human IGFBP-3.
921 10226800 The absence of 150-kDa insulin-like growth factor complexes in fetal rat serum is not due to a lack of functional acid-labile subunit.
922 10226800 Most of the insulin-like growth factors (IGFs) in adult rat or human plasma circulate in 150-kDa heterotrimeric complexes with IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit (ALS).
923 10226800 We report that ALS mRNA is expressed in term fetal rat liver at 30% of the levels in adult liver, that radioiodinated rat ALS is not proteolyzed by incubation with fetal rat serum, and that sufficient functional ALS is present in fetal rat serum to form 150-kDa complexes with recombinant human IGFBP-3.
924 10226801 Proteolysis of insulin-like growth factor binding protein-3 in serum from pregnant, non-pregnant and fetal rats by matrix metalloproteinases and serine proteases.
925 10226801 The insulin-like growth factors (IGFs) in adult mammalian plasma circulate predominantly in 150-kDa complexes that also contain IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit.
926 10226801 Recombinant human matrix metalloproteinase-3 (MMP-3) proteolyzed recombinant human IGFBP-3 or endogenous rat IGFBP-3 in non-pregnancy serum pretreated with AEBSF to inactivate endogenous serine proteases.
927 10334308 Phosphorylated insulin-like growth factor binding protein 1 is increased in pregnant diabetic subjects.
928 10396366 Insulin-like growth factor binding protein-1 in NIDDM: relationship with the insulin resistance syndrome.
929 10512758 Mitogenic and antiapoptotic effects of insulin-like growth factor binding protein-6 in the human osteoblastic osteosarcoma cell line Saos-2/B-10.
930 10512758 Insulin-like growth factor (IGF) I is a potent mitogen for human osteosarcoma cells such as the Saos-2/B-10 cell line.
931 10629166 In rats, OCT suppresses IGF-I mRNA expression and generation of serum and tissue IGF-I levels.
932 10629166 Serum levels of free IGF-I (P =0.39), IGF-II (P =0.54), and of the acid-labile subunit (ALS) of the ternary complex (P =0.50) were similar during GH+/-OCT as compared with GH alone.
933 10629166 After 1 week off GH treatment, significantly lower levels of IGF-I, IGF-II, IGFBP-3, and ALS were recorded (P<0.001).
934 10629166 In rats, OCT suppresses IGF-I mRNA expression and generation of serum and tissue IGF-I levels.
935 10629166 Serum levels of free IGF-I (P =0.39), IGF-II (P =0.54), and of the acid-labile subunit (ALS) of the ternary complex (P =0.50) were similar during GH+/-OCT as compared with GH alone.
936 10629166 After 1 week off GH treatment, significantly lower levels of IGF-I, IGF-II, IGFBP-3, and ALS were recorded (P<0.001).
937 10674577 Serum insulin-like growth factor binding protein-1 at 16 weeks and subsequent preeclampsia.
938 10694797 Glucose- and insulin-sensitive promoters were constructed by inserting glucose-responsive elements (GlREs) from the rat L-pyruvate kinase (L-PK) gene into the insulin-sensitive, liver-specific, rat insulin-like growth factor binding protein-1 (IGFBP-1) promoter.
939 10720056 Proteolysis of insulin-like growth factor-binding protein-3 is increased in urine from patients with diabetic nephropathy.
940 10720056 The insulin-like growth factor (IGF) system has been implicated in the development of experimental diabetic nephropathy.
941 10720056 IGFBP-3 proteolysis in urine from diabetic patients with normo- [albumin excretion rate (AER), <20 microg/min], micro- (AER, 20-200 microg/min), and macroalbuminuria (AER, >200 microg/min) was studied in 34 patients with noninsulin-dependent diabetes mellitus (NIDDM), 14 patients with insulin-dependent diabetes mellitus, and 9 controls.
942 10770191 The combination of insulin-like growth factor I and insulin-like growth factor-binding protein-3 reduces insulin requirements in insulin-dependent type 1 diabetes: evidence for in vivo biological activity.
943 10770191 Insulin-like growth factor-I (IGF-I) enhances insulin action in normal subjects and in patients with both type 1 and 2 diabetes; however, its administration is associated with significant side effects in a high percentage of patients.
944 10770191 The coadministration of IGF binding protein-3 (IGFBP-3, the predominant IGF binding protein in serum) with IGF-I limits IGF-I inducible side effects, but it does not attenuate the ability of IGF-I to enhance protein synthesis and bone accretion; therefore, we determined whether IGF-I/IGFBP-3 would retain biological activity in type 1 DM and limit side effects associated with free IGF-I administration.
945 10770191 Twelve patients received recombinant human IGF-I plus IGFBP-3 (2 mg/kg-day) by continuous sc infusion for 2 weeks.
946 10770191 During IGF-I/IGFBP-3, insulin doses were reduced by 49%, and mean serum glucose was reduced by 23%.
947 10770191 Free insulin levels obtained during frequent sampling in hospital fell 47% on IGF-I/IGFBP-3, compared with control, but showed no change with placebo.
948 10770191 IGFBP-2 (an IGF-I-dependent responsive variable) rose from 141 +/- 56 to 251 +/- 98 ng/mL (P < 0.01) on IGF-I/IGFBP-3.
949 10770191 To analyze the mechanism by which IGF-I/IGFBP-3 might reduce insulin requirements, the change in serum GH was quantified.
950 10770191 These findings indicate that IGF-I/IGFBP-3 is biologically active on carbohydrate metabolism, as measured by a decrease in insulin requirements in patients with type 1 diabetes.
951 10830291 Vascular endothelial growth factor and transforming growth factor-beta1 regulate the expression of insulin-like growth factor-binding protein-3, -4, and -5 in large vessel endothelial cells.
952 10830291 We investigated the effect of diabetes-associated growth factors on the expression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBPs) in cultured endothelial cells from bovine aorta.
953 10830291 Vascular endothelial growth factor inhibited IGFBP-3 mRNA (P < 0.01) and protein expression and increased IGFBP-5 mRNA (P < 0.001) and protein.
954 10830291 Transforming growth factor-beta1 inhibited IGFBP-3 (P < 0.01), IGFBP-4 (P < 0.01), and IGF-I mRNA expression, whereas at the protein level only IGFBP-3 was significantly decreased.
955 10830291 IGF-I, insulin, or angiotensin II did not affect IGF-I or IGFBP mRNA expression.
956 10830291 At the protein level, IGF-I clearly increased IGFBP-5 levels in conditioned medium.
957 10830291 In conclusion, vascular endothelial growth factor and transforming growth factor-beta1 regulate IGFBP expression in bovine aortic endothelial cells.
958 10856879 Regulation of insulin-like growth factor-binding protein-3 ternary complex in feline diabetes mellitus.
959 10856879 The 140 kDa ternary complex of insulin-like growth factor-binding protein-3 (IGFBP-3), IGFs and an acid-labile subunit (ALS) has previously been shown to be decreased in diabetes mellitus in humans and rats.
960 10856879 Total IGF-I concentrations, measured by RIA using des(1-3)-IGF-I as tracer were (+/-s.e.m.) 54+/-13 nmol/l in eight normal and 227+/-57 nmol/l in eight diabetic cats (P<0.01).
961 10856879 We conclude that (i) in contrast to humans and rats, ALS is the limiting factor for ternary complex formation in normal cats, (ii) ALS concentrations increase in feline diabetes mellitus and, by promoting ternary complex formation, this leads to an increase in total IGF-I concentrations, and (iii) total IGF-I concentrations may not be reliable in the diagnosis of acromegaly in diabetic cats.
962 10856879 Regulation of insulin-like growth factor-binding protein-3 ternary complex in feline diabetes mellitus.
963 10856879 The 140 kDa ternary complex of insulin-like growth factor-binding protein-3 (IGFBP-3), IGFs and an acid-labile subunit (ALS) has previously been shown to be decreased in diabetes mellitus in humans and rats.
964 10856879 Total IGF-I concentrations, measured by RIA using des(1-3)-IGF-I as tracer were (+/-s.e.m.) 54+/-13 nmol/l in eight normal and 227+/-57 nmol/l in eight diabetic cats (P<0.01).
965 10856879 We conclude that (i) in contrast to humans and rats, ALS is the limiting factor for ternary complex formation in normal cats, (ii) ALS concentrations increase in feline diabetes mellitus and, by promoting ternary complex formation, this leads to an increase in total IGF-I concentrations, and (iii) total IGF-I concentrations may not be reliable in the diagnosis of acromegaly in diabetic cats.
966 10856879 Regulation of insulin-like growth factor-binding protein-3 ternary complex in feline diabetes mellitus.
967 10856879 The 140 kDa ternary complex of insulin-like growth factor-binding protein-3 (IGFBP-3), IGFs and an acid-labile subunit (ALS) has previously been shown to be decreased in diabetes mellitus in humans and rats.
968 10856879 Total IGF-I concentrations, measured by RIA using des(1-3)-IGF-I as tracer were (+/-s.e.m.) 54+/-13 nmol/l in eight normal and 227+/-57 nmol/l in eight diabetic cats (P<0.01).
969 10856879 We conclude that (i) in contrast to humans and rats, ALS is the limiting factor for ternary complex formation in normal cats, (ii) ALS concentrations increase in feline diabetes mellitus and, by promoting ternary complex formation, this leads to an increase in total IGF-I concentrations, and (iii) total IGF-I concentrations may not be reliable in the diagnosis of acromegaly in diabetic cats.
970 10965886 Stimulation of insulin-like growth factor binding protein-1 synthesis by interleukin-1beta: requirement of the mitogen-activated protein kinase pathway.
971 10965886 Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is a 28-kDa plasma protein that binds to IGF-I and IGF-II with high affinity.
972 10965886 The purpose of the present study was to investigate the role of the MAP kinase pathway in regulating IGFBP-1 synthesis by IL-1beta.
973 10965886 We show that IL-1beta stimulates the phosphorylation of ERK-1 and -2 in a time- and dose-dependent manner.
974 10965886 In addition, the MAP kinase-kinase MEK-1 and the ribosomal S6-kinase RSK-1 are also phosphorylated in response to IL-1beta.
975 10965886 The transcription factor CREB, a potential substrate of both protein kinase A (PKA) and RSK-1, is phosphorylated in response to IL-1beta and cAMP in HepG2 cells.
976 10965886 The ability of IL-1beta to stimulate the expression of IGFBP-1 and the phosphorylation of the above kinases was specifically inhibited by PD98059, a MEK-1 inhibitor. cAMP also stimulated IGFBP-1 synthesis, but PD98059 failed to block the cAMP effect.
977 10965886 Conversely, a PKA inhibitor (H-89) inhibited the ability of cAMP, but not IL-1beta to stimulate IGFBP-1 synthesis.
978 10965886 The effect of IL-1beta and cAMP on IGFBP-1 messenger RNA (mRNA) accumulation was additive.
979 10965886 IL-1beta, cAMP, PD98059, and H-89 had similar effects on the accumulation of IGFBP-1 protein and mRNA.
980 10965886 IL-1beta and cAMP did not change the half-life of IGFBP-1 mRNA, but PD98059 and SB202190, a p38 MAP kinase inhibitor, destabilized IGFBP-1 mRNA and blocked the phosphorylation of RSK-1 in response to IL-1beta.
981 10965886 Our data demonstrate that the MAP kinase signal transduction pathway plays an important role in the regulation of IGFBP-1 synthesis by IL-1beta.
982 10973497 DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells.
983 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.
984 10973497 We find that the Caenorhabditis elegans protein DAF-16 binds the IGFBP-1 small middle dotIRE with specificity similar to that of the forkhead (FKH) factor(s) that act both to enhance glucocorticoid responsiveness and to mediate the negative effect of insulin at this site.
985 10973497 In HepG2 cells, DAF-16 and its mammalian homologs, FKHR, FKHRL1, and AFX, activate transcription through the IGFBP-1.IRE; this effect is inhibited by the viral oncoprotein E1A, but not by mutants of E1A that fail to interact with the coactivator p300/CREB-binding protein (CBP).
986 10973497 We show that DAF-16 and FKHR can interact with both the KIX and E1A/SRC interaction domains of p300/CBP, as well as the steroid receptor coactivator (SRC).
987 10973497 A C-terminal deletion mutant of DAF-16 that is nonfunctional in C. elegans fails to bind the KIX domain of CBP, fails to activate transcription through the IGFBP-1.IRE, and inhibits activation of the IGFBP-1 promoter by glucocorticoids.
988 10973497 Although AFX interacts with the KIX domain of CBP, it does not interact with SRC and does not respond to glucocorticoids or insulin.
989 10973497 Thus, we conclude that DAF-16 and FKHR act as accessory factors to the glucocorticoid response, by recruiting the p300/CBP/SRC coactivator complex to an FKH factor site in the IGFBP-1 promoter, which allows the cell to integrate the effects of glucocorticoids and insulin on genes that carry this site.
990 10973497 DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells.
991 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.
992 10973497 We find that the Caenorhabditis elegans protein DAF-16 binds the IGFBP-1 small middle dotIRE with specificity similar to that of the forkhead (FKH) factor(s) that act both to enhance glucocorticoid responsiveness and to mediate the negative effect of insulin at this site.
993 10973497 In HepG2 cells, DAF-16 and its mammalian homologs, FKHR, FKHRL1, and AFX, activate transcription through the IGFBP-1.IRE; this effect is inhibited by the viral oncoprotein E1A, but not by mutants of E1A that fail to interact with the coactivator p300/CREB-binding protein (CBP).
994 10973497 We show that DAF-16 and FKHR can interact with both the KIX and E1A/SRC interaction domains of p300/CBP, as well as the steroid receptor coactivator (SRC).
995 10973497 A C-terminal deletion mutant of DAF-16 that is nonfunctional in C. elegans fails to bind the KIX domain of CBP, fails to activate transcription through the IGFBP-1.IRE, and inhibits activation of the IGFBP-1 promoter by glucocorticoids.
996 10973497 Although AFX interacts with the KIX domain of CBP, it does not interact with SRC and does not respond to glucocorticoids or insulin.
997 10973497 Thus, we conclude that DAF-16 and FKHR act as accessory factors to the glucocorticoid response, by recruiting the p300/CBP/SRC coactivator complex to an FKH factor site in the IGFBP-1 promoter, which allows the cell to integrate the effects of glucocorticoids and insulin on genes that carry this site.
998 11071082 Insulin-like growth factor binding protein-1 as glucose regulator in adolescent boys with type 1 diabetes.
999 11081147 Increased levels of GH [122 micrograms/l], insulin-like growth factor (IGF-1) [830 micrograms/l], insulin-like growth factor binding protein 3 (IGFBP-3) [8.6 mg/l] and PRL [590 micrograms/l] were found.
1000 11081147 An eight-week trial of relatively low dose dopamine agonists led to a reduction of PRL, while the GH- and IGF-1 levels remained unchanged; the tumor showed only little shrinkage.
1001 11081147 After TSS, low levels of GH, IGF-1, and PRL documented a complete tumor removal, but persistent diabetes insipidus and anterior lobe deficits resulted from surgery.
1002 11095453 The effect of four weeks of supraphysiological growth hormone administration on the insulin-like growth factor axis in women and men.
1003 11095453 Measurements of serum insulin-like growth factor I (IGF-I) and related markers are routinely used in the diagnosis and treatment of GH deficiency and excess.
1004 11095453 Serum insulin-like growth factor I (IGF-I) levels in males receiving GH increased significantly through day 42 with no significant difference between the 2 doses.
1005 11095453 We conclude that 1) males are significantly more responsive than females to exogenous GH; 2) the increase in IGF-I is more robust compared with those in IGFBP-3 and ALS; 3) IGFBP-2 changes very little during GH treatment; and 4) among IGF-related substances, IGF-I is the most specific marker of supraphysiological GH exposure.
1006 11124266 In Caenorhabditis elegans, an insulin-like signaling pathway to phosphatidylinositol 3-kinase (PI 3-kinase) and AKT negatively regulates the activity of DAF-16, a Forkhead transcription factor.
1007 11124266 We show that in mammalian cells, C. elegans DAF-16 is a direct target of AKT and that AKT phosphorylation generates 14-3-3 binding sites and regulates the nuclear/cytoplasmic distribution of DAF-16 as previously shown for its mammalian homologs FKHR and FKHRL1.
1008 11124266 In vitro, interaction of AKT- phosphorylated DAF-16 with 14-3-3 prevents DAF-16 binding to its target site in the insulin-like growth factor binding protein-1 gene, the insulin response element.
1009 11124266 In HepG2 cells, insulin signaling to PI 3-kinase/AKT inhibits the ability of a GAL4 DNA binding domain/DAF-16 fusion protein to activate transcription via the insulin-like growth factor binding protein-1-insulin response element, but not the GAL4 DNA binding site, which suggests that insulin inhibits the interaction of DAF-16 with its cognate DNA site.
1010 11124266 Elimination of the DAF-16/1433 association by mutation of the AKT/14-3-3 sites in DAF-16, prevents 14-3-3 inhibition of DAF-16 DNA binding and insulin inhibition of DAF-16 function.
1011 11124266 In Caenorhabditis elegans, an insulin-like signaling pathway to phosphatidylinositol 3-kinase (PI 3-kinase) and AKT negatively regulates the activity of DAF-16, a Forkhead transcription factor.
1012 11124266 We show that in mammalian cells, C. elegans DAF-16 is a direct target of AKT and that AKT phosphorylation generates 14-3-3 binding sites and regulates the nuclear/cytoplasmic distribution of DAF-16 as previously shown for its mammalian homologs FKHR and FKHRL1.
1013 11124266 In vitro, interaction of AKT- phosphorylated DAF-16 with 14-3-3 prevents DAF-16 binding to its target site in the insulin-like growth factor binding protein-1 gene, the insulin response element.
1014 11124266 In HepG2 cells, insulin signaling to PI 3-kinase/AKT inhibits the ability of a GAL4 DNA binding domain/DAF-16 fusion protein to activate transcription via the insulin-like growth factor binding protein-1-insulin response element, but not the GAL4 DNA binding site, which suggests that insulin inhibits the interaction of DAF-16 with its cognate DNA site.
1015 11124266 Elimination of the DAF-16/1433 association by mutation of the AKT/14-3-3 sites in DAF-16, prevents 14-3-3 inhibition of DAF-16 DNA binding and insulin inhibition of DAF-16 function.
1016 11147791 Physiological differences in insulin-like growth factor binding protein-1 (IGFBP-1) phosphorylation in IGFBP-1 transgenic mice.
1017 11147791 Insulin-like growth factor binding protein (IGFBP)-1 has been shown to alter cellular responses to insulin-like growth factor 1 (IGF-1).
1018 11147791 Human IGFBP-1 undergoes serine phosphorylation, and this enhances both its affinity for IGF-1 by six- to eightfold and its capacity to inhibit IGF-1 actions.
1019 11147791 Scatchard analysis showed that the affinity of phosphorylated rat IGFBP-1 for IGF-1 was 3.9-fold higher than that of nonphosphorylated human IGFBP-1.
1020 11147791 The phosphorylation state of human IGFBP-1 may account for part of the phenotypic differences noted in the two studies of transgenic mice, and it is an important determinant of the capacity of human IGFBP-1 to inhibit IGF-1 actions in vivo.
1021 11147791 Physiological differences in insulin-like growth factor binding protein-1 (IGFBP-1) phosphorylation in IGFBP-1 transgenic mice.
1022 11147791 Insulin-like growth factor binding protein (IGFBP)-1 has been shown to alter cellular responses to insulin-like growth factor 1 (IGF-1).
1023 11147791 Human IGFBP-1 undergoes serine phosphorylation, and this enhances both its affinity for IGF-1 by six- to eightfold and its capacity to inhibit IGF-1 actions.
1024 11147791 Scatchard analysis showed that the affinity of phosphorylated rat IGFBP-1 for IGF-1 was 3.9-fold higher than that of nonphosphorylated human IGFBP-1.
1025 11147791 The phosphorylation state of human IGFBP-1 may account for part of the phenotypic differences noted in the two studies of transgenic mice, and it is an important determinant of the capacity of human IGFBP-1 to inhibit IGF-1 actions in vivo.
1026 11161963 Increased 24 h mean insulin-like growth factor binding protein-3 proteolytic activity in pubertal type 1 diabetic boys.
1027 11161963 The role of changes in insulin-like growth factor-I (IGF-I) bioavailability for the glycaemic control in these patients has not been completely elucidated.
1028 11161963 In particular, the possible role of increased IGF binding protein-3 (IGFBP-3) proteolysis reported in other insulin resistant states awaits further characterization.
1029 11161963 The aims of this study were to assess if hyperglycaemia in children with type 1 diabetes was associated with changes in free dissociable IGF-I (fdIGF-I) and IGF binding protein-3 protease activity (IGFBP-3-PA) and if increased insulin resistance during puberty was associated with changes in IGFBP-3-PA in healthy and diabetic children.
1030 11289492 Alterations in insulin-like growth factor binding protein-1 and sex hormone binding globulin levels in type 1 diabetic adolescents with microalbuminuria.
1031 11316739 Advanced glycosylation end products up-regulate connective tissue growth factor (insulin-like growth factor-binding protein-related protein 2) in human fibroblasts: a potential mechanism for expansion of extracellular matrix in diabetes mellitus.
1032 11316739 Connective tissue growth factor (CTGF), also known as insulin-like growth factor-binding protein-related protein-2 (IGFBP-rP2), is a potent inducer of extracellular matrix synthesis and angiogenesis and is increased in tissues from rodent models of diabetes.
1033 11316739 In contrast, mRNAs for other IGFBP superfamily members, IGFBP-rP1 (mac 25) and IGFBP-3, were not up-regulated by AGE.
1034 11316739 Reactive oxygen species as well as endogenous transforming growth factor-beta1 could not explain the AGE effect on CTGF mRNA.
1035 11316739 Advanced glycosylation end products up-regulate connective tissue growth factor (insulin-like growth factor-binding protein-related protein 2) in human fibroblasts: a potential mechanism for expansion of extracellular matrix in diabetes mellitus.
1036 11316739 Connective tissue growth factor (CTGF), also known as insulin-like growth factor-binding protein-related protein-2 (IGFBP-rP2), is a potent inducer of extracellular matrix synthesis and angiogenesis and is increased in tissues from rodent models of diabetes.
1037 11316739 In contrast, mRNAs for other IGFBP superfamily members, IGFBP-rP1 (mac 25) and IGFBP-3, were not up-regulated by AGE.
1038 11316739 Reactive oxygen species as well as endogenous transforming growth factor-beta1 could not explain the AGE effect on CTGF mRNA.
1039 11317665 Close relation of fasting insulin-like growth factor binding protein-1 (IGFBP-1) with glucose tolerance and cardiovascular risk in two populations.
1040 11443207 The inverse relationships between plasma insulin and insulin-like growth factor-binding protein-1 levels were maintained, suggesting persistent hepatic effects of insulin.
1041 11443207 Thus, the differences between congenital insulin deficiency vs. insulin receptor deficiency in humans may be explained by persistent insulinomimetic activity of the grossly elevated plasma insulin presumably being mediated through the type 1 insulin-like growth factor receptor.
1042 11586493 Altered lipid profile, leptin, insulin, and anthropometry in offspring of South Asian immigrants in the United States.
1043 11586493 The entire South Asian group had higher truncal skinfold thickness (40.1 +/- 18.1 and 30.3 +/- 12.6 mm, P = <.05) and lower insulin-like growth factor binding protein (IGFBP)-1 levels (46.8 +/- 33.4 and 56.0 +/- 33.4 microg/L, P =.05).
1044 11586493 A significant correlation between plasma leptin and insulin, triglycerides, TC, and body mass index (BMI) was seen in the South Asian males.
1045 11735249 Responses of insulin-like growth factor (IGF)-I and IGF-binding proteins to nutritional status in peroxisome proliferator-activated receptor-alpha knockout mice.
1046 11735249 In normal mice fasting IGF-I and the IGFBP-3 ternary complex were 2-fold higher in males than in females.
1047 11735249 Compared to wild type, male PPARalpha-/- mice had 40% lower total fasting IGF-I concentrations, decreased ALS and less IGFBP-3 ternary complex formation, but within 4 h of refeeding there was an increase in IGF-I and IGFBP-3 ternary complex to values similar to controls.
1048 11735249 IGFBP-1 and insulin concentrations were higher in males than females, and were increased by PPARalpha knockout, suggesting significant hepatic insulin resistance.
1049 11739083 IGFBP-3 binding to endothelial cells inhibits plasmin and thrombin proteolysis.
1050 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.
1051 11739083 IGFBP-3 and IGFBP-4, and their chimeras IGFBP-3(4) and IGFBP-4(3), were treated with plasmin and with thrombin, proteases known to cleave IGFBP-3.
1052 11739083 IGFBP-3 was highly susceptible to plasmin, whereas IGFBP-4 was less so.
1053 11739083 Substitution of the P3 region for the P4 region in IGFBP-4 (IGFBP-4(3)) increased the ability of the protease to digest IGFBP-4(3); substitution of the P4 region for the P3 region in IGFBP-3 (IGFBP-3(4)) decreased the digestion of IGFBP-3(4).
1054 11739083 When 125I-labeled IGFBP-3 or 125I-IGFBP-4(3) was first bound to vascular endothelial cells, subsequent proteolysis by either plasmin or thrombin was substantially inhibited.
1055 11739083 We conclude that the P3 region is central to proteolysis of IGFBP-3 by plasmin and thrombin, processes which were inhibited by association of IGFBP-3 with endothelial cells.
1056 11807812 Insulin-like growth factor binding protein-2 mediates the inhibition of DNA synthesis by transforming growth factor-beta in mink lung epithelial cells.
1057 11807812 Insulin-like growth factor binding protein-3 (IGFBP-3) has been proposed to mediate the growth inhibitory effects of transforming growth factor (TGF)-beta in breast and prostate cancer cells.
1058 11807812 Both TGF-beta and exogenous IGFBP-3 inhibit DNA synthesis in Mv1 mink lung epithelial cells (CCL64).
1059 11807812 Leu(60)-IGF-I also decreased the inhibition of CCL64 DNA synthesis by TGF-beta by up to 70%, whereas Long-R3-IGF-I, an IGF-I analog with higher affinity for IGF-I receptors than for IGFBPs, did not decrease inhibition, suggesting that the effect of Leu(60)-IGF-I resulted from its forming complexes with endogenous IGFBPs.
1060 11807812 Leu(60)-IGF-I did not decrease TGF-beta stimulation of a Smad3-dependent reporter gene.
1061 11807812 If exogenous and secreted IGFBP-2 must bind to CCL64 cells to inhibit DNA synthesis, Leu(60)-IGF-I might reduce the inhibition of DNA synthesis by bIGFBP-2 or TGF-beta by inhibiting the association of IGFBP-2 in the media with CCL64 cells.
1062 11807812 Since TGF-beta does not increase IGFBP-2 abundance, we propose that TGF-beta sensitizes CCL64 cells to the latent growth inhibitory activity of endogenous IGFBP-2 by potentiating an intracellular IGFBP-2 signaling pathway or by promoting the association of secreted IGFBP-2 with the plasma membrane.
1063 11807812 Insulin-like growth factor binding protein-2 mediates the inhibition of DNA synthesis by transforming growth factor-beta in mink lung epithelial cells.
1064 11807812 Insulin-like growth factor binding protein-3 (IGFBP-3) has been proposed to mediate the growth inhibitory effects of transforming growth factor (TGF)-beta in breast and prostate cancer cells.
1065 11807812 Both TGF-beta and exogenous IGFBP-3 inhibit DNA synthesis in Mv1 mink lung epithelial cells (CCL64).
1066 11807812 Leu(60)-IGF-I also decreased the inhibition of CCL64 DNA synthesis by TGF-beta by up to 70%, whereas Long-R3-IGF-I, an IGF-I analog with higher affinity for IGF-I receptors than for IGFBPs, did not decrease inhibition, suggesting that the effect of Leu(60)-IGF-I resulted from its forming complexes with endogenous IGFBPs.
1067 11807812 Leu(60)-IGF-I did not decrease TGF-beta stimulation of a Smad3-dependent reporter gene.
1068 11807812 If exogenous and secreted IGFBP-2 must bind to CCL64 cells to inhibit DNA synthesis, Leu(60)-IGF-I might reduce the inhibition of DNA synthesis by bIGFBP-2 or TGF-beta by inhibiting the association of IGFBP-2 in the media with CCL64 cells.
1069 11807812 Since TGF-beta does not increase IGFBP-2 abundance, we propose that TGF-beta sensitizes CCL64 cells to the latent growth inhibitory activity of endogenous IGFBP-2 by potentiating an intracellular IGFBP-2 signaling pathway or by promoting the association of secreted IGFBP-2 with the plasma membrane.
1070 11960310 The IDDM13 region containing the insulin-like growth factor binding protein-5 (IGFBP5) gene on chromosome 2q33-q36 and the genetic susceptibility to rheumatoid arthritis.
1071 11960310 IGFBP5 is located in a region where an insulin-dependent diabetes mellitus (IDDM) susceptibility locus, IDDM13 (2q33-q36), has been mapped.
1072 11960310 Previous evidence that non-MHC IDDM loci overlap RA susceptibility loci made IGFBP5 and its region an interesting candidate locus which was tested for linkage.
1073 11960310 Forty-nine sibships (2-4 affected siblings per sibship) with RA were genotyped with microsatellite markers covering an 11.2 cM interval in the IGFBP5/IDDM13 region.
1074 11994362 Body composition and circulating levels of insulin, insulin-like growth factor-binding protein-1 and growth hormone (GH)-binding protein affect the pharmacokinetics of GH in adults independently of age.
1075 11994362 The MCR was unrelated to age, but was negatively correlated to baseline concentrations of IGF-binding protein-1 (IGFBP-1; r = -0.53, P < 0.01) and positively correlated to basal levels of insulin (r = 0.46; P < 0.05), GH-binding protein (GHBP; r = 0.52; P < 0.01), IGFBP-3 (r = 0.47; P < 0.05), and total body fat (r = 0.44; P < 0.05).
1076 11994362 GH infusion caused significant changes in the concentrations of IGF-I, free fatty acids, GHBP, IGFBP-1, and insulin, but none of these effects was correlated to age.
1077 11994362 Based on our results we conclude that 1) the clearance of GH is concentration dependent; 2) the pharmacokinetics and acute effects of GH are not affected by age per se; and 3) basal levels of insulin, IGFBP-1, and GHBP as well as age-related changes in body composition are important predictors of GH pharmacokinetics.
1078 12063638 As expected, insulin concentrations rose sixfold and insulin like growth factor binding protein 1 concentrations fell by 20 % with glucose loading.
1079 12127303 Glucagon and GLP-1 stimulate IGFBP-1 secretion in Hep G2 cells without effect on IGFBP-1 mRNA.
1080 12127303 Glucagon has previously been reported to increase serum levels of insulin-like growth factor binding protein-1 (IGFBP-1) in humans.
1081 12127303 In contrast to forskolin the peptides glucagon and GLP-1 had no effect on IGFBP-1 mRNA at 3, 6 and 24 h incubation or any detectable effect on the apparent half-life of IGFBP-1 mRNA.
1082 12127303 However, the exposure to glucagon (10 microg/mL, 2.87 microM) and GLP-1 (1 microM) caused a two-fold stimulation in protein levels of IGFBP-1 after 6 h incubation, declining to control levels after 24 h.
1083 12127303 The regulation of IGFBP-1 secretion by glucagon and GLP-1 appeared to be cAMP independent.
1084 12145180 Low circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) are closely associated with the presence of macrovascular disease and hypertension in type 2 diabetes.
1085 12145180 Posttranslational phosphorylation of IGFBP-1 significantly increases its affinity for IGF-I and therefore represents a further mechanism for controlling IGF bioavailability.
1086 12145180 In contrast, levels of nonphosphorylated and lesser-phosphorylated IGFBP-1 (lpIGFBP-1) were unrelated to macrovascular disease or hypertension but did correlate positively with fasting glucose concentration (rho = 0.350, P < 0.01). tIGFBP-1 concentrations were higher in subjects treated with insulin alone (n = 29) than for any other group.
1087 12235108 In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS).
1088 12235108 Liver IGF-1-deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively.
1089 12235108 Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis.
1090 12235108 In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS).
1091 12235108 Liver IGF-1-deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively.
1092 12235108 Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis.
1093 12235108 In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS).
1094 12235108 Liver IGF-1-deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively.
1095 12235108 Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis.
1096 12519211 Endometrial function in vervet monkeys (Cercopithecus aethiops): morphology, beta3 integrin and insulin-like growth factor binding protein-1 expression during the menstrual cycle and pregnancy in the normal and disrupted endometrium.
1097 12519211 The expression of endometrial beta3 integrin and insulin-like growth factor binding protein-1 (IGFBP-1) was studied in cycling and pregnant vervet monkeys.
1098 12519211 Endometrial function in vervet monkeys (Cercopithecus aethiops): morphology, beta3 integrin and insulin-like growth factor binding protein-1 expression during the menstrual cycle and pregnancy in the normal and disrupted endometrium.
1099 12519211 The expression of endometrial beta3 integrin and insulin-like growth factor binding protein-1 (IGFBP-1) was studied in cycling and pregnant vervet monkeys.
1100 12750235 Similarly, no associations were observed for the ratio of total cholesterol:HDL-cholesterol, triglycerides, and insulin-like growth factor binding protein 1.
1101 12750235 However, those in the highest fourth of glycosylated hemoglobin (HbA(1c)) level had a slightly increased risk of colorectal cancer (OR, 1.57; 95% CI, 0.94-2.60; P(trend) = 0.02).
1102 12818085 [Insulin-like growth factor 1 (somatomedin C) and its binding proteins 1 and 3 in children with special consideration of diabetes].
1103 12818085 Insulin-like growth factor 1 (IGF-1, somatomedin C) belongs to a family of polypeptide hormones, which are structurally close relatives of insulin.
1104 12818085 Somatomedin circulates in plasma in complex with a family of binding proteins. 85-95% of total IGF-1 is found in the complex consisting of IGF-1, binding protein 3 and ALS.
1105 12818085 After binding with IGFBP-1, IGFBP-2 and IGFBP-6, IGF-1 passes through epithelium and reaches the target cells.
1106 12818085 Insulin-like growth factors may be involved in the etiopathogenesis of diabetes and in diabetes complications.
1107 12868196 [Growth hormone, insulin-like growth factor and insulin-like growth factor binding protein in young type I diabetes patients with the onset of diabetic angiopathy].
1108 12914928 Insulin rapidly and completely inhibits expression of the hepatic insulin-like growth factor binding protein-1 (IGFBP-1), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) genes.
1109 12914928 However, we recently found that the regulation of the IGFBP1 but not the PEPCK or G6Pase genes by insulin was sensitive to rapamycin, an inhibitor of mTOR.
1110 12917205 Determinants of circulating insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations in a cohort of Singapore men and women.
1111 12917205 Variation in the circulating concentrations of the insulin-like growth factor (IGF) system has been implicated in the etiology of chronic diseases including cancer (prostate, breast, colon, and lung), heart disease, type 2 diabetes, and osteoporosis.
1112 12917205 We searched for sociodemographic, anthropometric, reproductive, lifestyle, and dietary determinants of IGF-I and insulin-like growth factor binding protein (IGFBP) -3 serum concentrations.
1113 12917205 Radioimmunometrically measured IGF-I and IGFBP-3 concentrations were available for 312 men and 326 postmenopausal women ages 50 years or older.
1114 12917205 Mean IGF-I concentrations were 144 ng/ml and 121 ng/ml for men and women, respectively (gender difference, P < 0.0001), and mean IGFBP-3 concentrations were 3710 ng/ml and 4147 ng/ml for men and women, respectively (gender difference, P < 0.0001).
1115 12917205 IGF-I and IGFBP-3 decreased with age (P for trend <0.0001); the age-related decrease in the IGF-I:IGFBP-3 molar ratio was stronger in women than men.
1116 12917205 Intake of calcium from food and supplement was associated positively with circulating IGF-I, IGFBP-3, and molar ratio.
1117 12917205 Determinants of circulating insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations in a cohort of Singapore men and women.
1118 12917205 Variation in the circulating concentrations of the insulin-like growth factor (IGF) system has been implicated in the etiology of chronic diseases including cancer (prostate, breast, colon, and lung), heart disease, type 2 diabetes, and osteoporosis.
1119 12917205 We searched for sociodemographic, anthropometric, reproductive, lifestyle, and dietary determinants of IGF-I and insulin-like growth factor binding protein (IGFBP) -3 serum concentrations.
1120 12917205 Radioimmunometrically measured IGF-I and IGFBP-3 concentrations were available for 312 men and 326 postmenopausal women ages 50 years or older.
1121 12917205 Mean IGF-I concentrations were 144 ng/ml and 121 ng/ml for men and women, respectively (gender difference, P < 0.0001), and mean IGFBP-3 concentrations were 3710 ng/ml and 4147 ng/ml for men and women, respectively (gender difference, P < 0.0001).
1122 12917205 IGF-I and IGFBP-3 decreased with age (P for trend <0.0001); the age-related decrease in the IGF-I:IGFBP-3 molar ratio was stronger in women than men.
1123 12917205 Intake of calcium from food and supplement was associated positively with circulating IGF-I, IGFBP-3, and molar ratio.
1124 14498768 Somatomedin-1 binding protein-3: insulin-like growth factor-1 binding protein-3, insulin-like growth factor-1 carrier protein.
1125 14498768 Somatomedin-1 binding protein-3 [insulin-like growth factor-1 binding protein-3, SomatoKine] is a recombinant complex of insulin-like growth factor-1 (rhIGF-1) and binding protein-3 (IGFBP-3), which is the major circulating somatomedin (insulin-like growth factor) binding protein; binding protein-3 regulates the delivery of somatomedin-1 to target tissues.
1126 14527633 Specifically, hyperinsulinemia elevates serum concentrations of free insulin-like growth factor-1 (IGF-1) and androgens, while simultaneously reducing insulin-like growth factor-binding protein 3 (IGFBP-3) and sex hormone-binding globulin (SHBG).
1127 14527633 Since IGFBP-3 is a ligand for the nuclear retinoid X receptor alpha, insulin-mediated reductions in IGFBP-3 may also influence transcription of anti-proliferative genes normally activated by the body's endogenous retinoids.
1128 14700556 High levels of 150-kDa insulin-like growth factor binding protein three ternary complex in patients with acromegaly and the effect of pegvisomant-induced serum IGF-I normalization.
1129 14722613 The growth retardation was associated with a greater than 60-fold increase in the expression of hepatic insulin-like growth factor binding protein-1.
1130 15194686 Insulin-response element-binding protein 1: a novel Akt substrate involved in transcriptional action of insulin.
1131 15194686 In this report, we identified a novel transcription factor that binds and transactivates the insulin-response elements of the insulin-like growth factor-binding protein-3 and other insulin responsive genes.
1132 15194686 This factor is a target of insulin signal transduction downstream of the phosphatidylinositol 3'-kinase/protein kinase B (Akt) pathway.
1133 15194686 Identification of a novel target of Akt that appears to mediate signals specific for insulin action should provide further insight into the mechanism of insulin action at the genomic level.
1134 15220193 Here we investigated whether the addition of exendin-4, a hormone that stimulates insulin secretion and beta-cell replication and differentiation, improves induction of remission by ALS.
1135 15220193 Transient treatment of overtly diabetic NOD mice with ALS and exendin-4 achieved complete remission in 23 of 26 mice (88%) within 75 days, accompanied by progressive normalization of glucose tolerance, improved islet histology, increased insulin content in the pancreas, and insulin release in response to a glucose challenge.
1136 15220193 Here we investigated whether the addition of exendin-4, a hormone that stimulates insulin secretion and beta-cell replication and differentiation, improves induction of remission by ALS.
1137 15220193 Transient treatment of overtly diabetic NOD mice with ALS and exendin-4 achieved complete remission in 23 of 26 mice (88%) within 75 days, accompanied by progressive normalization of glucose tolerance, improved islet histology, increased insulin content in the pancreas, and insulin release in response to a glucose challenge.
1138 15242989 To understand the role of the GH/IGF-I axis in liver regeneration, we performed partial hepatectomies in three groups of mice: GH antagonist (GHa) transgenic mice, in which the action of GH is blocked; liver IGF-I-deficient mice that lack IGF-I specifically in the liver and also lack the acid-labile subunit (ALS; LID+ALSKO mice), in which IGF-I levels are very low and GH secretion is increased; and control mice.
1139 15358277 Moreover, newer diagnostic tools, such as high-resolution neuroimaging, measurements of serum insulin-like growth factor 1 and insulin-like growth factor-binding protein 3, and an increasing number of genetic tests, have emerged.
1140 15554902 Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure.
1141 15554902 To study the function of the PDK1 (3-phosphoinositide-dependent protein kinase-1) signalling pathway in mediating insulin's actions in the liver, we employed CRE recombinase/loxP technology to generate L(liver)-PDK1-/- mice, which lack expression of PDK1 in hepatocytes and in which insulin failed to induce activation of PKB in liver.
1142 15554902 The glucose intolerance of the L-PDK1-/- mice may be due to an inability of glucose to suppress hepatic glucose output through the gluconeogenic pathway, since the mRNA encoding hepatic PEPCK (phosphoenolpyruvate carboxykinase), G6Pase (glucose-6-phosphatase) and SREBP1 (sterol-regulatory-element-binding protein 1), which regulate gluconeogenesis, are no longer controlled by feeding.
1143 15554902 Furthermore, three other insulin-controlled genes, namely IGFBP1 (insulin-like-growth-factor-binding protein-1), IRS2 (insulin receptor substrate 2) and glucokinase, were regulated abnormally by feeding in the liver of PDK1-deficient mice.
1144 15554902 These results establish that the PDK1 signalling pathway plays an important role in regulating glucose homoeostasis and controlling expression of insulin-regulated genes.
1145 15598684 Insulin-like growth factor binding protein-1 is independently affected by ethnicity, insulin sensitivity, and leptin in healthy, glucose-tolerant young men.
1146 15598684 We examined the relationships among IGF binding protein (IGFBP)-1, insulin sensitivity, and leptin in different ethnic groups (Asian Indians, Chinese, and Caucasians) using the euglycemic hyperinsulinemic clamp.
1147 15598684 IGFBP-1, insulin, and leptin were measured after fasting and during the clamp.
1148 15598684 The ratio of insulin to IGFBP-1 at fasting and throughout the euglycemic clamp was higher in Asian Indians.
1149 15598684 Fasting IGFBP-1 had a strong negative correlation with fasting leptin levels (r = -0.715, P = 0.001).
1150 15598684 Multiple linear regression demonstrated that fasting insulin, leptin, ethnicity, and insulin sensitivity were significant predictors for fasting IGFBP-1.
1151 15598684 IGFBP-1 is independently determined by ethnicity, insulin sensitivity, and leptin in glucose-tolerant men.
1152 15598684 The presence of relative insulin resistance and low fasting IGFBP-1 levels in Asian Indians may contribute to their higher risk of developing diabetes and cardiovascular disease.
1153 15613437 Sex hormone-binding globulin and insulin-like growth factor-binding protein-1 as indicators of metabolic syndrome, cardiovascular risk, and mortality in elderly men.
1154 15613437 Two binding proteins, SHBG and IGF-binding protein-1 (IGFBP-1), are both down-regulated by insulin and therefore could serve as potential indicators of the metabolic syndrome and hyperinsulinemia-related cardiovascular risk.
1155 15613437 We compared serum SHBG and IGFBP-1 as potential markers of abnormal glucose tolerance, the metabolic syndrome, diabetes mellitus, cardiovascular risk factors, and total, cardiovascular, and coronary heart disease mortality in elderly men.
1156 15613437 Low SHBG and IGFBP-1 were both associated with an increased prevalence of abnormal glucose tolerance and the metabolic syndrome, but only SHBG was associated with diabetes mellitus.
1157 15613437 SHBG was less influenced by body mass index than IGFBP-1.
1158 15613437 It is concluded that low SHBG is a better indicator of increased cardiovascular mortality than low or high IGFBP-1.
1159 15625284 Circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 are associated with early carotid atherosclerosis.
1160 15645308 When mated with an acid-labile subunit (ALS) gene-deleted mouse they also show osteopenia suggesting that circulating IGF-I levels play a significant role in bone formation.
1161 15645308 In a separate transgenic mouse we created a model of severe insulin resistance and type 2 diabetes by the overexpression of a dominant-negative IGF-I receptor in skeletal muscle.
1162 15673562 Kidney growth in normal and diabetic mice is not affected by human insulin-like growth factor binding protein-1 administration.
1163 15673562 Insulin-like growth factor I (IGF-I) accumulates in the kidney following the onset of diabetes, initiating diabetic renal hypertrophy.
1164 15673562 It has been suggested that IGF-I is trapped in the kidney by IGF binding protein 1 (IGFBP-1).
1165 15673562 Human IGFBP-1 administration had no effect on increased kidney weight or albuminuria in early diabetes, although it abolished renal cortical IGF-I accumulation and glomerular hypertrophy in diabetic mice.
1166 15673562 Increased IGF-I levels in kidneys of normal mice receiving hIGFBP-1 were not reflected on kidney parameters.
1167 15736102 Altered response of insulin-like growth factor-binding protein 1 to nutritional deprivation in type 2 diabetes mellitus.
1168 15736102 Circulating insulin-like growth factor-binding protein 1 (IGFBP-1) normally has a close inverse relationship to insulin secretion, which results in a characteristic diurnal variation.
1169 15736102 However, in type 2 diabetes the correlation with insulin may be lost and IGFBP-1 concentrations relatively increased.
1170 15736102 During refeeding after nutritional deprivation the IGFBP-1 response to insulin was restored in the individuals with diabetes.
1171 15736102 In conclusion, patients with type 2 diabetes mellitus have altered IGFBP-1 regulation, relating to impaired hepatic insulin sensitivity, which improves after a period of energy (caloric) restriction.
1172 15736102 Altered response of insulin-like growth factor-binding protein 1 to nutritional deprivation in type 2 diabetes mellitus.
1173 15736102 Circulating insulin-like growth factor-binding protein 1 (IGFBP-1) normally has a close inverse relationship to insulin secretion, which results in a characteristic diurnal variation.
1174 15736102 However, in type 2 diabetes the correlation with insulin may be lost and IGFBP-1 concentrations relatively increased.
1175 15736102 During refeeding after nutritional deprivation the IGFBP-1 response to insulin was restored in the individuals with diabetes.
1176 15736102 In conclusion, patients with type 2 diabetes mellitus have altered IGFBP-1 regulation, relating to impaired hepatic insulin sensitivity, which improves after a period of energy (caloric) restriction.
1177 15777106 Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3.
1178 15777106 Insmed is developing mecasermin rinfabate, a recombinant complex of insulin-like growth factor-I (rhIGF-I) and binding protein-3 (rhIGFBP-3) [insulin-like growth factor-I/insulin-like growth factor binding protein-3, rhIGF-I/rhIGFBP-3, SomatoKine], for a number of metabolic and endocrine indications.
1179 15777106 In the human body, IGF-I circulates in the blood bound to a binding protein-3 (IGFBP-3), which regulates the delivery of IGF-I to target tissues, and particular proteases clip them apart in response to stresses and release IGF-I as needed.
1180 15777106 For the treatment of IGF-I deficiency, it is desirable to administer IGF-I bound to IGFBP-3 to maintain the normal equilibrium of these proteins in the blood.
1181 15777106 Insmed has acquired an exclusive licence to Pharmacia's regulatory filings concerning yeast-derived insulin-like growth factor 1 (IGF-1).
1182 15777106 In January 2004, Insmed obtained a non-exclusive licence to the patents for use of IGF-I for the treatment of extreme or severe insulin-resistant diabetes from Fujisawa Pharmaceutical.
1183 15777106 Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3.
1184 15777106 Insmed is developing mecasermin rinfabate, a recombinant complex of insulin-like growth factor-I (rhIGF-I) and binding protein-3 (rhIGFBP-3) [insulin-like growth factor-I/insulin-like growth factor binding protein-3, rhIGF-I/rhIGFBP-3, SomatoKine], for a number of metabolic and endocrine indications.
1185 15777106 In the human body, IGF-I circulates in the blood bound to a binding protein-3 (IGFBP-3), which regulates the delivery of IGF-I to target tissues, and particular proteases clip them apart in response to stresses and release IGF-I as needed.
1186 15777106 For the treatment of IGF-I deficiency, it is desirable to administer IGF-I bound to IGFBP-3 to maintain the normal equilibrium of these proteins in the blood.
1187 15777106 Insmed has acquired an exclusive licence to Pharmacia's regulatory filings concerning yeast-derived insulin-like growth factor 1 (IGF-1).
1188 15777106 In January 2004, Insmed obtained a non-exclusive licence to the patents for use of IGF-I for the treatment of extreme or severe insulin-resistant diabetes from Fujisawa Pharmaceutical.
1189 15787669 Effect of maternal diabetes on phosphorylation of insulin-like growth factor binding protein-1 in cord serum.
1190 15914054 Insulin-like growth factor binding protein (IGFBP)-6 is unique among IGFBPs for its IGF-II binding specificity.
1191 15914054 IGFBP-6 inhibits growth of a number of IGF-II-dependent cancers, including rhabdomyosarcoma, neuroblastoma and colon cancer.
1192 15914054 Although the major action of IGFBP-6 appears to be inhibition of IGF-II actions, a number of studies suggest that it may also have IGF-independent actions.
1193 15914054 Both the N-terminal and C-terminal domains of IGFBP-6 contribute to high affinity IGF binding, and the C-terminal domain appears to confer its IGF-II specificity.
1194 15914054 The three-dimensional structure of the C-domain of IGFBP-6 contains a thyroglobulin type 1 fold, and the IGF-II binding site is located in the proximal half of this domain adjacent to the glycosaminoglycan binding site.
1195 15914054 This is particularly significant since IGFBP-6 provides an attractive basis for therapy of IGF-II-dependent tumors.
1196 15935983 Insulin-like growth factor binding protein-3 mediates cytokine-induced mesangial cell apoptosis.
1197 15935983 Insulin-like growth factors (IGFs) and their high affinity binding proteins (IGFBPs) exert major actions on mesangial cell survival, but their underlying mechanisms remain unclear.
1198 15935983 Anti-sense IGFBP-3 oligo at 10 microg/mL significantly inhibited apoptosis induced by 100 ng/mL TNF-alpha, serum-free conditions, or high (25 mM) glucose.
1199 15935983 Increased IGFBP-3 release associated with high ambient glucose or TNF-alpha was inhibited by pre-treatment with anti-sense oligo.
1200 15935983 Under serum-free conditions, recombinant human IGFBP-3 blocked Akt phosphorylation at threonine 308 (pThr308), whereas anti-sense oligo treatment was associated with enhanced pThr308 activity.
1201 15935983 In summary, these data support a novel mechanism for TNF-alpha-induced mesangial cell apoptosis mediated by IGFBP-3 and present regulation of pThr308 activity as a novel mechanism underlying IGFBP-3 action.
1202 15959422 Cord serum insulin-like growth factor binding protein-1 and -3: effect of maternal diabetes and relationships to fetal growth.
1203 15966854 Early investigations into the insulin-like growth factor (IGF)-independent actions of insulin-like growth factor-binding protein (IGFBP)-3 have implicated a large array of signaling proteins with links to cell cycle control and apoptosis.
1204 16081485 Isolation and validation of human prepubertal skeletal muscle cells: maturation and metabolic effects of IGF-I, IGFBP-3 and TNFalpha.
1205 16081485 We have developed a primary skeletal muscle cell culture model derived from normal prepubertal children to investigate the effects of insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and tumour necrosis factor alpha (TNFalpha) on growth, differentiation and metabolism.
1206 16081485 Differentiation was confirmed biochemically by an increase in creatine kinase (CK) activity and IGFBP-3 secretion over time.
1207 16081485 IGF-I promoted whilst TNFalpha inhibited myoblast proliferation, differentiation and IGFBP-3 secretion.
1208 16081485 IGF-I partially rescued the cells from the inhibiting effects of TNFalpha.
1209 16081485 Compared to adult myoblast cultures, children's skeletal muscle cells demonstrated higher basal and day 7 CK activities, increased levels of IGFBP-3 secretion, diminished IGF-I/TNFalpha action and absence of the inhibitory effect of exogenous IGFBP-3 on differentiation.
1210 16081485 Additional studies demonstrated that TNFalpha increased basal glucose transport via GLUT1, nitric oxide synthase and p38MAPK-dependent mechanisms.
1211 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.
1212 16176184 GSK3 inhibition in liver reduces expression of the gluconeogenic genes PEPCK (phosphoenolpyruvate carboxykinase), G6Pase (glucose-6-phosphatase), as well as IGFBP1 (insulin-like growth factor binding protein-1).
1213 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.
1214 16189247 Recombinant, nonglycosylated human insulin-like growth factor-binding protein-3 (IGFBP-3) is degraded preferentially after administration to type II diabetics, resulting in increased endogenous glycosylated IGFBP-3.
1215 16275148 Novel actions of IGFBP-3 on intracellular signaling pathways of insulin-secreting cells.
1216 16275148 We recently reported insulin-like growth factor binding protein-3 (IGFBP-3) as a novel mediator of apoptosis in insulin-secreting cells.
1217 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.
1218 16275148 By immunoblot, we demonstrate that G(56)G(80)G(81)-IGFBP-3 suppresses phosphorylation of c-raf-MEK-ERK pathway and p38 kinase in time-dependent and dose-dependent manners.
1219 16275148 SAPK/JNK signaling was unaffected.
1220 16275148 These data delineate several novel intracellular sites of action for IGFBP-3 in insulin-secreting cells.
1221 16355814 Serum zinc, insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in children with type 1 diabetes mellitus.
1222 16369209 Insulin and insulin-like growth factors (IGFs) belong to the most biologically characterized family of peptides involved in metabolism, growth and development.
1223 16369209 The IGF-I receptor is a member of the family of tyrosine kinase growth factor receptors, and is highly homologous (70%) to the insulin receptor, especially in the tyrosine kinase domain (84%) ADDIN.
1224 16369209 However, most of the circulating IGF-I associates with a high molecular weight complex approximately 150 KDa consisting of IGFBP-3 and the acid labile subunit (ALS) ADDIN.
1225 16415018 In particular, insulin-like growth factor-binding protein 1 was down-regulated in the HBX mouse liver.
1226 16549931 Acute interleukin-6 infusion increases IGFBP-1 but has no short-term effect on IGFBP-3 proteolysis in healthy men.
1227 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.
1228 16549931 In addition, IL-6 alters the hepatic expression of insulin-like growth factor-I (IGF-I) and the IGFBPs in vitro.
1229 16549931 The aim of the present study was to investigate whether moderately elevated IL-6 levels have short-term effects on circulating IGF-I, IGFBP-1 and IGFBP-3 proteolysis in vivo.
1230 16549931 Free IGF-I, total IGF-I, IGFBP-1, insulin and cortisol were measured using immunoassays.
1231 16549931 We found that IL-6 concentrations reaching approximately 100 pg/ml significantly increased IGFBP-1 after the end of infusion in the absence of changes in insulin.
1232 16549931 There was no effect of IL-6 on IGFBP-3 proteolysis, total IGF-I or free dissociable IGF-I.
1233 16549931 These data suggest that moderately elevated levels of IL-6 such as in the post-operative state or after exercise may contribute to increased levels of IGFBP-1.
1234 16549931 Although this study does not exclude that high levels and/or prolonged exposure to IL-6 may induce IGFBP-3 proteolysis in sepsis or chronic inflammatory disease, it suggests that IL-6 released from exercising skeletal muscle is not directly involved in proteolysis of circulating IGFBP-3.
1235 16556765 Low insulin-like growth factor binding protein-2 expression is responsible for increased insulin receptor substrate-1 phosphorylation in mesangial cells from mice susceptible to glomerulosclerosis.
1236 16556765 However, IGF-I, IGF-I receptor, and IRS-1 protein levels were induced by exposure to 25 mm glucose in both cell lines.
1237 16556765 Addition of exogenous IGFBP-2 partially blunted the effect of 25 mm glucose on IRS-1 phosphorylation in ROP MC.
1238 16556765 Finally, addition of exogenous IGFBP-2 in ROP MC partially blunted the effect of high glucose on IRS-1 phosphorylation and might have a protective role.
1239 16610982 There has been interest in using recombinant human (rh) insulin-like growth factor (IGF)-I (rhIGF-I) to treat short stature, either alone or in combination with its binding protein (insulin-like growth factor binding protein [IGFBP]-3).
1240 16610982 In addition, the serum half-life of unbound rhIGF-I is shorter when administered to patients with GHIS, who have low serum concentrations of its binding proteins IGFBP-3 and acid-labile subunit (ALS), than when administered to normal volunteers or to the patient with an IGF-I gene deletion (who had normal levels of IGFBP-3). iPlex (mecasermin rinfabate), an equimolar mixture of IGF-I and its binding protein IGFBP-3, was developed to prolong the half-life and to counteract acute adverse events (particularly hypoglycaemia) associated with administration of IGF-I.
1241 16610982 There has been interest in using recombinant human (rh) insulin-like growth factor (IGF)-I (rhIGF-I) to treat short stature, either alone or in combination with its binding protein (insulin-like growth factor binding protein [IGFBP]-3).
1242 16610982 In addition, the serum half-life of unbound rhIGF-I is shorter when administered to patients with GHIS, who have low serum concentrations of its binding proteins IGFBP-3 and acid-labile subunit (ALS), than when administered to normal volunteers or to the patient with an IGF-I gene deletion (who had normal levels of IGFBP-3). iPlex (mecasermin rinfabate), an equimolar mixture of IGF-I and its binding protein IGFBP-3, was developed to prolong the half-life and to counteract acute adverse events (particularly hypoglycaemia) associated with administration of IGF-I.
1243 16793770 Nonsecreted insulin-like growth factor binding protein-3 (IGFBP-3) can induce apoptosis in human prostate cancer cells by IGF-independent mechanisms without being concentrated in the nucleus.
1244 16793770 Insulin-like growth factor binding protein-3 (IGFBP-3), a secreted protein, has the intrinsic ability to induce apoptosis directly without binding insulin-like growth factors.
1245 16793770 Nonsecreted insulin-like growth factor binding protein-3 (IGFBP-3) can induce apoptosis in human prostate cancer cells by IGF-independent mechanisms without being concentrated in the nucleus.
1246 16793770 Insulin-like growth factor binding protein-3 (IGFBP-3), a secreted protein, has the intrinsic ability to induce apoptosis directly without binding insulin-like growth factors.
1247 16862465 Pregnancy-induced changes in insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and acid-labile subunit (ALS) in patients with growth hormone (GH) deficiency and excess.
1248 16915540 Insulin-like growth factor binding protein-2 (IGFBP-2) is a marker for the metabolic syndrome.
1249 17237715 Insulin-like growth factor binding protein-3 induces insulin resistance in adipocytes in vitro and in rats in vivo.
1250 17237715 Insulin-like growth factor binding protein (IGFBP)-3 binds to IGF and modulates their actions and also possesses intrinsic activities.
1251 17237715 We investigated its effects on insulin action and found that when IGFBP-3 was added to fully differentiated 3T3-L1 adipocytes in culture, insulin-stimulated glucose transport was significantly inhibited to 60% of control in a time- and dose-dependent manner.
1252 17237715 Tumor necrosis factor (TNF)-alpha treatment also inhibited glucose transport to the same degree as IGFBP-3 and, in addition, increased IGFBP-3 levels 3-fold.
1253 17237715 Co-treatment with TNF-alpha and IGFBP-3 antisense partially prevented the inhibitory effect of TNF-alpha on glucose transport, indicating a role for IGFBP-3 in cytokine-induced insulin resistance.
1254 17237715 Insulin-stimulated phosphorylation of the insulin receptor was markedly decreased by IGFBP-3 treatment.
1255 17237715 IGFBP-3 treatment suppressed adiponectin expression in 3T3-L1 adipocytes.
1256 17237715 These in vitro and in vivo findings demonstrate that IGFBP-3 has potent insulin-antagonizing capability and suggest a role for IGFBP-3 in cytokine-induced insulin resistance and other mechanisms involved in the development of type-2 diabetes.
1257 17237715 Insulin-like growth factor binding protein-3 induces insulin resistance in adipocytes in vitro and in rats in vivo.
1258 17237715 Insulin-like growth factor binding protein (IGFBP)-3 binds to IGF and modulates their actions and also possesses intrinsic activities.
1259 17237715 We investigated its effects on insulin action and found that when IGFBP-3 was added to fully differentiated 3T3-L1 adipocytes in culture, insulin-stimulated glucose transport was significantly inhibited to 60% of control in a time- and dose-dependent manner.
1260 17237715 Tumor necrosis factor (TNF)-alpha treatment also inhibited glucose transport to the same degree as IGFBP-3 and, in addition, increased IGFBP-3 levels 3-fold.
1261 17237715 Co-treatment with TNF-alpha and IGFBP-3 antisense partially prevented the inhibitory effect of TNF-alpha on glucose transport, indicating a role for IGFBP-3 in cytokine-induced insulin resistance.
1262 17237715 Insulin-stimulated phosphorylation of the insulin receptor was markedly decreased by IGFBP-3 treatment.
1263 17237715 IGFBP-3 treatment suppressed adiponectin expression in 3T3-L1 adipocytes.
1264 17237715 These in vitro and in vivo findings demonstrate that IGFBP-3 has potent insulin-antagonizing capability and suggest a role for IGFBP-3 in cytokine-induced insulin resistance and other mechanisms involved in the development of type-2 diabetes.
1265 17316097 Insulin-like growth factor binding protein-1 to screen for insulin resistance in children.
1266 17351286 Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1/MAC25) is linked to endothelial-dependent vasodilation in high-ferritin type 2 diabetes.
1267 17479439 The divergent effect of insulin-like growth factor binding protein (IGFBP) - 1 on IGF-induced Steroidogenesis in bovine adrenocortical cells is not due to its phosphorylation status.
1268 17479439 In previous studies we have shown that insulin-like growth factor (IGF)-II stimulates basal as well as ACTH-induced cortisol secretion from bovine adrenocortical cells more potently than IGF-I.
1269 17479439 The steroidogenic effect of both, IGF-I and IGF-II, is mediated through the IGF-I receptor and modified by locally produced IGF binding proteins.
1270 17479439 Further studies demonstrate that bovine adrenocortical cells do synthesize IGFBP-1 to -4 and that their secretion is regulated differentially by IGFs and ACTH.
1271 17479439 Coincubation of bovine adrenocortical cells with purified IGFBP-1 (30 nM) induced a time--and dose-dependent potentiating effect (38+/-2%) on IGF-I-stimulated (6.5 nM) cortisol-secretion, wheras the IGF-II induced steroidogenic effect was inhibited (40+/-3%) by IGFBP-1.
1272 17479439 In order to evaluate the influence of different phosphorylation states of IGFBP-1 on the steroidogenic effect of IGF-I and IGF-II and on the affinity to IGFs, a highly phosphorylated (pIGFBP-1) and a dephosphorylated isoform (dIGFBP-1) of IGFBP-1 have been separated by anion exchange chromatography for further incubation experiments and binding studies.
1273 17479439 No different effects on IGF-I or IGF-II-induced steroidogenesis were observed when a highly phosphorylated IGFBP-1 isoform was used, compared to the dephosphorylated IGFBP-1 isoforms.
1274 17479439 In binding studies IGFBP-1 did show high affinity binding for IGF-I with a calculated association constant (K (a)) of 2,17 x 10 (9) M (-1).
1275 17479439 IN CONCLUSION, these results demonstrate that in bovine adrenocortical cells IGFBP-1 time- and dose-dependently inhibits the steroidogenic effect of IGF-II and stimulates the effect of IGF-I.
1276 17479439 The previously observed stronger steroidogenic potency of IGF-II in bovine adrenocortical cells therefore can not be explained by an interaction with IGFBP-1.
1277 17479439 The mechanisms by which IGFBP-1 divergently regulates the steroidogenic effect of IGF-I and IGF-II remain unclear at present and further investigation is necessary to elucidate the mechanisms by which IGFBP-1 modulates IGF action in the adult adrenal gland.
1278 17594780 Insulin-like growth factor binding protein-1 is an emerging marker which may be useful in this context.
1279 17655506 Calpain proteolysis of insulin-like growth factor binding protein (IGFBP) -2 and -3, but not of IGFBP-1.
1280 17655506 Calpains are cytoplasmic Ca(2+)-regulated cysteine proteases that may regulate insulin-like growth factor (IGF)-independent actions of insulin-like growth factor binding proteins (IGFBPs) through IGFBP proteolysis.
1281 17655506 In this study, [(125)I]-labeled IGFBP-2 and -3, but not IGFBP-1, were proteolyzed by Ca(2+)-activated m-calpain in vitro.
1282 17655506 Degradation of higher concentrations of the recombinant proteins IGFBP-2 and -3 by m-calpain was dose-dependent, but was terminated within 20 min by autolysis.
1283 17655506 By subjecting proteolytic fragments to N-terminal amino acid sequence analysis, the primary cleavage sites in IGFBP-2 and -3 were localized to the non-conserved central linker regions.
1284 17655506 Using the biosensor technique, in vitro binding of m-calpain to IGFBP-3 was demonstrated to be a Ca(2+)-dependent reaction with a rapid on/off rate.
1285 17693389 Attenuation of insulin secretion by insulin-like growth factor binding protein-1 in pancreatic beta-cells.
1286 17693389 Incubation of dispersed mouse beta-cells with IGFBP-1 for 30min inhibited insulin secretion stimulated by glucose, glucagon-like peptide 1 (GLP-1) or tolbutamide without changes in basal release of insulin and in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and NAD(P)H evoked by glucose.
1287 17693389 In contrast, IGFBP-1 augmented glucose-stimulated insulin secretion in intact islets, associated with a reduced somatostatin secretion.
1288 17693389 These results suggest a suppressive action of IGFBP-1 on insulin secretion in isolated beta-cells through a mechanism distal to energy generating steps and not involving regulation of [Ca(2+)](i).
1289 17693389 In contrast, IGFBP-1 amplifies glucose-stimulated insulin secretion in intact islets, possibly by suppressing somatostatin secretion.
1290 17693389 These direct modulatory influences of IGFBP-1 on insulin secretion may imply an important regulatory role of IGFBP-1 in vivo and in the pathogenesis of type 2 diabetes, in which loss of insulin release is an early pathogenetic event.
1291 17959403 An N-terminal fragment of insulin-like growth factor binding protein-3 (IGFBP-3) induces apoptosis in human prostate cancer cells in an IGF-independent manner.
1292 18068478 Localization of increased insulin-like growth factor binding protein-3 in diabetic rat penis: implications for erectile dysfunction.
1293 18162523 Induction of apoptosis in human prostate cancer cells by insulin-like growth factor binding protein-3 does not require binding to retinoid X receptor-alpha.
1294 18162523 Binding to RXR-alpha has been proposed to be required for IGFBP-3 to induce apoptosis.
1295 18162523 A COOH-terminal region in IGFBP-3 (residues 215-232) contains a nuclear localization signal, and binding domains for RXR-alpha and heparin (HBD).
1296 18162523 Different combinations of the 11 amino acids in this region that differ from IGFBP-1, a related IGFBP, which does not localize to the nucleus or bind RXR-alpha, were mutated to the IGFBP-1 sequence.
1297 18162523 IGFBP-3 binding to glutathione S-transferase-RXR-alpha only was lost when all 11 sites were mutated (HBD-11m-IGFBP-3).
1298 18162523 Expressed nuclear RXR-alpha did not transport cytoplasmic IGFBP-3 nuclear localization signal mutants that can bind RXR-alpha to the nucleus even after treatment with RXR ligand.
1299 18162523 We conclude that in PC-3 cells, RXR-alpha is not required for the nuclear translocation of IGFBP-3 and that IGFBP-3 can induce apoptosis in human prostate cancer cells without binding RXR-alpha.
1300 18496669 Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men.
1301 18952711 Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism.
1302 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).
1303 18952711 Phenotypic comparisons of controls and four mouse lines with genetic IGF-1 deficits-liver-specific IGF-1 deficiency (LID), ALS knockout (ALSKO), IGFBP-3 (BP3) knockout, and a triply deficient LID/ALSKO/BP3 line-produced several novel findings. 1) All deficient strains had decreased serum IGF-1 levels, but this neither predicted growth potential or skeletal integrity nor defined growth hormone secretion or metabolic abnormalities. 2) IGF-1 deficiency affected development of both cortical and trabecular bone differently, effects apparently dependent on the presence of different circulating IGF-1 complexes. 3) IGFBP-3 deficiency resulted in increased linear growth.
1304 18952711 Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism.
1305 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).
1306 18952711 Phenotypic comparisons of controls and four mouse lines with genetic IGF-1 deficits-liver-specific IGF-1 deficiency (LID), ALS knockout (ALSKO), IGFBP-3 (BP3) knockout, and a triply deficient LID/ALSKO/BP3 line-produced several novel findings. 1) All deficient strains had decreased serum IGF-1 levels, but this neither predicted growth potential or skeletal integrity nor defined growth hormone secretion or metabolic abnormalities. 2) IGF-1 deficiency affected development of both cortical and trabecular bone differently, effects apparently dependent on the presence of different circulating IGF-1 complexes. 3) IGFBP-3 deficiency resulted in increased linear growth.
1307 19164337 Serum insulin-like growth factor binding protein-1: an improvement over other simple indices of insulin sensitivity in the assessment of subjects with normal glucose tolerance.
1308 19297224 Low levels of insulin-like growth-factor-binding protein-1 (IGFBP-1) are prospectively associated with the incidence of type 2 diabetes and impaired glucose tolerance (IGT): the Söderåkra Cardiovascular Risk Factor Study.
1309 19408737 [Insulin-like growth factor-binding protein-1: a new biochemical marker of nonalcoholic fatty liver disease?].
1310 19463807 Biological variation in fasting serum insulin-like growth factor binding protein-1 (IGFBP-1) among individuals with a varying glucose tolerance.
1311 19477944 Unraveling insulin-like growth factor binding protein-3 actions in human disease.
1312 19477944 Interestingly, apart from the ability to inhibit or enhance IGF actions, IGFBP-3 also exhibits very clear, distinct biological effects independent of the IGF/IGF-I receptor axis.
1313 19477944 This review reinforces the concept in support of the IGF/IGF-IR axis-independent actions of IGFBP-3 and delineates potential underlying mechanisms involved and subsequent biological significance, focusing in particular on functional binding partners and the clinical significance of IGFBP-3 in the assessment of cancer risk.
1314 19771387 Insulin-like growth factor binding protein: a possible marker for the metabolic syndrome?
1315 19771387 Insulin-like growth factor (IGF) binding proteins (IGFBPs) moved on to contain both IGF high- and low-affinity binders, exerting mitogenic and metabolic actions through its complex interplay between IGF/insulin and its IGF/insulin-independent manner.
1316 19786971 Associations of insulin-like growth factor binding protein-3 gene polymorphisms with IGF-I activity and lipid parameters in adolescents.
1317 19897600 Role of insulin-like growth factor-binding protein 5 (IGFBP5) in organismal and pancreatic beta-cell growth.
1318 19897600 A major effector of the insulin/IGF-I signaling pathway, the serine/threonine protein kinase Akt, mediates cellular processes such as glucose uptake, protein synthesis, cell survival, and growth.
1319 19897600 IGF-I is required for normal organismal growth, and in the pancreatic beta-cell, the insulin/IGF-I signaling pathway is critical for normal and adaptive maintenance of beta-cell mass.
1320 19897600 Although IGFBP5 is identified as a gene induced by Akt1 activation in the beta-cell, Igfbp5 expression is not necessary for myrAkt1 to augment beta-cell size or mass in vivo.
1321 20007694 The insulin-like growth factor-1 binding protein acid-labile subunit alters mesenchymal stromal cell fate.
1322 20007694 Age-related osteoporosis is accompanied by an increase in marrow adiposity and a reduction in serum insulin-like growth factor-1 (IGF-1) and the binding proteins that stabilize IGF-1.
1323 20007694 To determine the relationship between these proteins and bone marrow adiposity, we evaluated the adipogenic potential of marrow-derived mesenchymal stromal cells (MSCs) from mice with decreased serum IGF-1 due to knockdown of IGF-1 production by the liver or knock-out of the binding proteins.
1324 20007694 We found that expression of the late adipocyte differentiation marker peroxisome proliferator-activated receptor gamma was increased in marrow isolated from ALSKO mice.
1325 20007694 MSCs from ALSKO mice also exhibited decreased alkaline-phosphatase positive colony size in cultures that were stimulated with osteoblast differentiation media.
1326 20007694 These osteoblast-like cells from ALSKO mice failed to induce osteoclastogenesis of control cells in co-culture assays, indicating that impairment of IGF-1 complex formation with ALS in bone marrow alters cell fate, leading to increased adipogenesis.
1327 20061427 Serum insulin-like growth factor-binding protein-2 levels and metabolic and cardiovascular risk factors in young adults and children born small for gestational age.
1328 20134415 Aims of the study were to measure insulin-like growth factor-binding protein-2 (IGFBP-2) expression by abdominal subcutaneous adipocytes and to assess the relationship between IGFBP-2 expression, circulating IGFBP-2, obesity, and insulin sensitivity in obese children.
1329 20134415 Serum free and total IGF-I, IGFBP-2, adiponectin, and leptin were measured.
1330 20134415 Circulating IGFBP-2 was positively associated with insulin sensitivity, in agreement with previous studies.
1331 20134415 IGFBP-2 expression was associated with fat mass percentage (r = 0.656; P < 0.02), insulin sensitivity (r = -0.604; P < 0.05), free IGF-I (r = 0.646; P < 0.05), and leptin (r = 0.603; P < 0.05), but not with circulating IGFBP-2 (r = 0.003, P = ns).
1332 20134415 The association between IGFBP-2 expression and adiposity (r = 0.648; P < 0.05) was independent of insulin sensitivity (covariate).
1333 20134415 In conclusion, circulating IGFBP-2 was positively associated with insulin sensitivity.
1334 20134415 IGFBP-2 was expressed by subcutaneous abdominal adipocytes of obese children and increased with adiposity, independently from the level of insulin sensitivity.
1335 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.
1336 20499371 Insulin-like growth factor 1 (IGF-1) is a crucial mediator of body size and bone mass during growth and development.
1337 20499371 In serum, IGF-1 is stabilized by several IGF-1-binding proteins (IGFBPs) and the acid labile subunit (ALS).
1338 20630940 Proteomic analysis identifies insulin-like growth factor-binding protein-related protein-1 as a podocyte product.
1339 20630940 As validation, we confirmed that one of these proteins, insulin-like growth factor-binding protein-related protein-1 (IGFBP-rP1), was expressed in mRNA and protein of cultured podocytes.
1340 20630940 In addition, transforming growth factor-β1 stimulation increased IGFBP-rP1 in conditioned medium.
1341 20630940 IGFBP-rP1 was absent from podocytes of normal mice and was expressed in podocytes and pseudocrescents of transgenic mice, where it was coexpressed with desmin, a podocyte injury marker.
1342 20630940 Proteomic analysis identifies insulin-like growth factor-binding protein-related protein-1 as a podocyte product.
1343 20630940 As validation, we confirmed that one of these proteins, insulin-like growth factor-binding protein-related protein-1 (IGFBP-rP1), was expressed in mRNA and protein of cultured podocytes.
1344 20630940 In addition, transforming growth factor-β1 stimulation increased IGFBP-rP1 in conditioned medium.
1345 20630940 IGFBP-rP1 was absent from podocytes of normal mice and was expressed in podocytes and pseudocrescents of transgenic mice, where it was coexpressed with desmin, a podocyte injury marker.
1346 20711952 Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells.
1347 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).
1348 20711952 Vitamin D stimulates ovarian steroidogenesis and IGFBP-1 production in human ovarian cells likely acting via vitamin D receptor.
1349 20711952 Vitamin D also enhances inhibitory effect of insulin on IGFBP-1 production.
1350 20855548 Fetal exposure to altered amniotic fluid glucose, insulin, and insulin-like growth factor-binding protein 1 occurs before screening for gestational diabetes mellitus.
1351 20926583 Evidence of a role for insulin-like growth factor binding protein (IGFBP)-3 in metabolic regulation.
1352 20926583 Fasting blood glucose and insulin levels were significantly elevated in IGFBP-3(-/-) mice.
1353 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.
1354 20926583 In summary, glucose tolerance and clamp testing indicate that IGFBP-3(-/-) mice preserve insulin sensitivity despite evidence of increased basal glucose turnover and hepatic steatosis.
1355 21127808 These studies specifically show effects on the glucose transporter (GLUT-4) gene and protein; insulin-like growth factor binding protein-1 (IGFBP-1); nuclear transcription factor kappa B (NFκB); tumor necrosis factor alpha (TNF-α); and insulin production.
1356 21628395 Understanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging.
1357 21628395 IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues.
1358 21628395 To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice).
1359 21628395 The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or 'free IGF1'.
1360 21628395 We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels.
1361 21628395 Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type.
1362 21628395 The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions.
1363 21628395 Understanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging.
1364 21628395 IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues.
1365 21628395 To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice).
1366 21628395 The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or 'free IGF1'.
1367 21628395 We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels.
1368 21628395 Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type.
1369 21628395 The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions.
1370 22396199 The latter is characterized by dysregulation of the Akt, AMP-activated protein kinase (AMPK), and IGF-I pathways and expression of microRNAs (miRNAs).
1371 22396199 Two-week treatment with TCM was associated with activation of AMPK, Akt, and insulin-like growth factor-binding protein (IGFBP)1 pathways, with downregulation of miR29-b and expression of a gene network implicated in cell cycle, intermediary, and NADPH metabolism with normalization of CYP7a1 and IGFBP1 expression.
1372 22522884 Upregulation of plasma insulin-like growth factor binding protein 2 levels after biliopancreatic diversion in humans.
1373 22522884 The insulin-like growth factor (IGF) binding protein 2 (IGFBP-2) is a 36 kDa circulating protein that has been recently suggested to modulate insulin sensitization and fat accumulation.
1374 22522884 In humans, a low-circulating concentration of IGFBP-2 has been associated with obesity and insulin resistance.
1375 22522884 Changes in IGFBP-2 concentrations were significantly and negatively associated with blood glucose, insulin, triglycerides, and total cholesterol levels.
1376 22522884 The mechanisms for the augmentation in IGFBP-2 after BPD-DS and its contribution to insulin sensitization remain to be elucidated.
1377 22689104 Serum IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels and two polymorphisms in IGF-1 gene (rs35767, rs17032362) were investigated.While mean IGF-1 SDS value was lower in study group (p=0.002), no difference was detected between mean IGFBP-3 SDS values.
1378 22689104 Comparing the cases with wild type, homozygous and heterozygous carriers for both polymorphisms with respect to height, weight, BMI, IGF-1 and IGFBP-3 SDS values, no significant difference was detected.IGF-1 SDS levels of patients with ISS were significantly lower compared to control group.
1379 22689104 No effect of IGF-1 gene rs35767 and rs17032362 polymorphisms on stature, IGF-1 and IGFBP-3 levels could be demonstrated.
1380 22884472 Posttranslational modifications of the insulin-like growth factor-binding protein 3 in patients with type 2 diabetes mellitus assessed by affinity chromatography.
1381 22884472 Structural and ligand-binding properties of the insulin-like growth factor-binding protein (IGFBP)-3 in patients with poorly controlled diabetes mellitus type 2 were investigated using boronic acid- and lectin-affinity chromatography.
1382 22884472 Posttranslational modifications of the insulin-like growth factor-binding protein 3 in patients with type 2 diabetes mellitus assessed by affinity chromatography.
1383 22884472 Structural and ligand-binding properties of the insulin-like growth factor-binding protein (IGFBP)-3 in patients with poorly controlled diabetes mellitus type 2 were investigated using boronic acid- and lectin-affinity chromatography.
1384 22976122 Studies linking insulin-like growth factor-1 (IGF-1) to age-related bone loss in humans have been reported but remain only correlative.
1385 22976122 In this investigation, we characterized the bone phenotype of aged WT C57BL/6J male mice in comparison to that of C57BL/6J mice with reduced serum IGF-1 levels arising from an igfals gene deletion (ALS knockout (ALSKO)).
1386 23015654 Insulin-like growth factor-I and insulin-like growth factor binding protein-3 in Alzheimer's disease.
1387 23488611 A novel mutation in IGFALS, c.380T>C (p.L127P), associated with short stature, delayed puberty, osteopenia and hyperinsulinaemia in two siblings: insights into the roles of insulin growth factor-1 (IGF1).
1388 23583762 In particular, mice expressing reduced levels of VEGF suffer from late-onset motor neuron degeneration, whereas VEGF delivery significantly delays motor neuron death in ALS mouse models, at least partly through neuroprotective effects.
1389 23583762 Specifically, VEGF decreased expression of the stress-related gene activating transcription factor 3 (ATF3) in DRG neurons isolated from streptozotocin-induced diabetic mice (ex vivo) and in isolated DRG neurons exposed to high glucose concentrations (in vitro).
1390 23583762 A small synthetic VEGF mimicking pentadecapeptide (QK) exerted similar effects on DRG cultures: the peptide reduced ATF3 expression in vitro and ex vivo in paclitaxel- and hyperglycemia-induced models of neuropathy to a similar extent as the full-length recombinant VEGF protein.
1391 23583762 By using transgenic mice selectively overexpressing the VEGF receptor 2 in postnatal neurons, these neuroprotective effects were shown to be mediated through VEGF receptor 2.
1392 23607045 Serum samples were analyzed for calcium, phosphorus, albumin, creatinine, alkaline phosphatase, 25 (OH) vitamin D3, intact parathormone (PTH) levels (both cases and controls) and HbA1c, antimicrosomal and IgA tissue transglutaminase (IgA TTG) antibodies, cortisol, follicle stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG), tetraiodothyronine (T4), thyroid stimulating hormone (TSH), growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein 3 (IGFBP3) (cases only).
1393 23607045 Linear regression analysis showed that low BMD in T1DM patients was associated with poor glycaemic control, lower IGF-1 levels, less physical activity (in total population as well as in male and female subgroups), and lower body fat percentage (in females) and higher alkaline phosphatase level (in males) (P < 0.05).
1394 23696565 FoxC2(AD)(+/Tg) mice are lean and insulin-sensitive and have high bone mass due to increased bone formation associated with high bone turnover.
1395 23696565 Conditioned media (CM) collected from forkhead box c2 (FOXC2)-induced beige adipocytes activated the osteoblast phenotype and increased levels of phospho-AKT and β-catenin in recipient cells.
1396 23696565 Immunodepletion of CM with antibodies against wingless related MMTV integration site 10b (WNT10b) and insulin-like growth factor binding protein 2 (IGFBP2) resulted in the loss of pro-osteoblastic activity, and the loss of increase in the levels of phospho-AKT and β-catenin.
1397 23696565 Conversely, CM derived from cells overexpressing IGFBP2 or WNT10b restored osteoblastic activity in recipient cells.
1398 23935929 Microarray analysis revealed that SPARC depletion upregulated the expression of interleukin 11 (IL11), KISS1, insulin-like growth factor binding protein 4 (IGFBP4), collagen type I alpha 1 (COLIA1), matrix metallopeptidase 9 (MMP9), and downregulated the expression of the alpha polypeptide of chorionic gonadotropin (CGA), MMP1, gap junction protein alpha 1 (GJA1), et al.
1399 23963811 Since insulin-like growth factor binding protein 2 (IGFBP2) has been shown to be independently associated with obesity and diabetes risk, we examined the IGF-IGFBP axis in male rat offspring following either maternal UN or maternal obesity to explain possible common pathways in the development of metabolic disorders.
1400 23963811 Circulating IGF-1 and IGFBP3 levels and hepatic mRNA expression of IGFBP1 and IGFBP2 were significantly decreased in UN and HF offspring compared to CONT.
1401 15496506 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces insulin-like growth factor binding protein-1 gene expression and counteracts the negative effect of insulin.
1402 15496506 We studied the regulation of insulin-like growth factor binding protein-1 (IGFBP-1), a protein involved in glucose homeostasis and whose expression is down-regulated by insulin.
1403 15496506 This XRE, located near the insulin-glucocorticoid regulatory region, binds the aryl-hydrocarbon receptor.
1404 15496506 In agreement with previous studies, the IGFBP-1 promoter was down-regulated by insulin (50%); we show here that although TCDD activated the IGFBP-1 promoter 5- to 6-fold, the combination of TCDD and insulin led to an expression level of IGFBP-1 that was higher than basal level (2- to 3-fold activation).
1405 15496506 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces insulin-like growth factor binding protein-1 gene expression and counteracts the negative effect of insulin.
1406 15496506 We studied the regulation of insulin-like growth factor binding protein-1 (IGFBP-1), a protein involved in glucose homeostasis and whose expression is down-regulated by insulin.
1407 15496506 This XRE, located near the insulin-glucocorticoid regulatory region, binds the aryl-hydrocarbon receptor.
1408 15496506 In agreement with previous studies, the IGFBP-1 promoter was down-regulated by insulin (50%); we show here that although TCDD activated the IGFBP-1 promoter 5- to 6-fold, the combination of TCDD and insulin led to an expression level of IGFBP-1 that was higher than basal level (2- to 3-fold activation).