Ignet

Gene Pair Information

Gene Pair: INS, PDX1

Related Sentences

#	PMID	Sentence
1	8922372	Among the two important transcription factors for insulin gene expression, IEF1 is present both in alpha- and beta-cells, but PDX-1/IPF1/STF-1/IDX-1, a homeodomain-containing transcription factor, is present in beta-cells but not in alpha-cells.
2	8922372	The exogenous expression of PDX-1 in alphaTC1.6 cells alone could induce islet amyloid polypeptide (IAPP) mRNA expression in the cells but not the expression of insulin, glucokinase, or GLUT2 gene.
3	8922372	However, when betacellulin was added to the medium, the PDX-1-expressing alphaTC1.6 cells, but not the control alphaTC1.6 cells, came to express insulin and glucokinase mRNAs.
4	8922372	These observations demonstrate the potency of PDX-1 for the expression of the insulin, glucokinase, and IAPP genes and suggest that certain regulatory factors, which can partially be modified by betacellulin, also contribute to the beta-cell specificity of gene expression.
5	11117522	PDX-1 binds to and transactivates the promoters of several physiologically relevant genes within the beta-cell, including insulin, glucose transporter 2, glucokinase, and islet amyloid polypeptide.
6	11117522	This study focuses on the mechanisms by which PDX-1 activates insulin gene transcription.
7	11117522	These results suggest that the PDX-1 transactivation domain is specifically required for appropriate regulation of insulin enhancer function in beta-cells.
8	11181516	Nuclear IDX-1 protein levels on Western blots were increased by ectopic Hh expression, thereby providing a mechanism for Hh-mediated regulation of the insulin promoter.
9	11181516	We propose that Hh signaling activates the insulin gene promoter indirectly via the direct activation of IDX-1 expression.
10	11270685	Nes2y cells, both variants showed about a 50% reduction in their ability to activate insulin gene transcription compared to wild-type IPF1, as measured by reporter gene assay.
11	11781323	These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets.
12	11904435	The loss in beta-cell function in Pdx-1(+/-)/Hnf-3beta(+/-) mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-1(+/-)/Hnf-1alpha(+/-) mice.
13	11978636	In fact, overexpression of both Pdx-1 and Isl-1 in IEC-6 cells (Isl-YK-12, -14, and -15 cells) gave them the ability to express insulin without exposure to betacellulin.
14	12011047	These results were correlated with changes in the binding of the important transcription factor PDX-1 to the insulin promoter; adenoviral overexpression of DN-JNK preserved PDX-1 DNA binding activity in the face of oxidative stress, whereas wild type JNK overexpression decreased PDX-1 DNA binding activity.
15	12684063	That the effects of Mad on insulin expression were mediated through PDX-1 was further substantiated by studies showing inhibition of insulin promoter activation by Mad in the presence of mutated PDX-1 binding site.
16	12684063	Such regulation of insulin expression by Mad with modulation of PDX-1 expression and DNA binding activity could offer useful therapeutic and/or experimental tools to promote insulin production in appropriate cell types.
17	12783165	The glucagonoma cell line InR1G9 was transduced with a Pdx1-encoding lentiviral vector and insulin and glucagon mRNA levels were analysed by northern blot and real-time PCR.
18	12783165	In glucagonoma cells transduced with a Pdx1-encoding lentiviral vector, insulin gene expression was induced while glucagon mRNA levels were reduced by 50 to 60%.
19	12829640	The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription.
20	12829640	These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology.
21	14509268	We conclude that dexamethasone inhibits insulin expression in pancreatic beta-cells via a mechanism involving down-regulation of Pdx-1 and induction of C/EBPbeta.
22	15001545	PDX-1 interacts with multiple transcription factors and coregulators, including the coactivator p300, to activate the transcription of the insulin gene and other target genes within pancreatic beta-cells.
23	15001545	Several mutant PDX-1 proteins that are associated with heritable forms of diabetes in humans, in particular the mutant P63fsdelC, exhibited increased binding to a carboxy-terminal segment of p300 in the setting of decreased DNA-binding activities, suggesting that sequestration of p300 by mutant PDX-1 proteins may be an additional mechanism by which insulin gene expression is reduced in heterozygous carriers of pdx-1(ipf-1) mutations.
24	15001545	Impairment of interactions between PDX-1 and p300 in pancreatic beta-cells may limit insulin production and lead to the development of diabetes.
25	15144884	However, the role of Pdx-1 in the regulation of insulin release is not well established.
26	15144884	In the present study, we identified a new target of Pdx-1 involved in insulin release.
27	15153417	These events appear to correlate with pdx-1 gene expression and its ability to bind the insulin gene.
28	15562255	GLUT4+/-;PDX-1+/- mice developed beta-cell hyperplasia but failed to increase their beta-cell insulin content.
29	15743769	Chromatin immunoprecipitation assays revealed that the decrease in insulin transcription was associated with decreases in the occupancies of Pdx-1 and p300 at the proximal insulin promoter.
30	15743769	Our results suggest that Pdx-1 directly regulates insulin transcription through formation of a complex with transcriptional coactivators on the proximal insulin promoter.
31	15756539	The severely impaired proinsulin processing combined with decreased GLP-1R expression and cellular cAMP content, rather than metabolic defects or altered exocytosis, may contribute to the beta cell dysfunction induced by Pdx-1 deficiency.
32	16166097	In correlation with this degradation, we observed a subsequent reduction in the activation of the insulin promoter and a decrease in PDX-1-mediated gene expression, i.e. glut2 and glucokinase.
33	16280646	When oxidative stress was induced in vitro in beta cells, the insulin gene promoter activity and mRNA levels were suppressed, accompanied by the reduced activity of pancreatic and duodenal homeobox factor-1 (PDX-1) (also known as IDX-1/STF-1/IPF1), an important transcription factor for the insulin gene.
34	16309850	Incretin hormones have trophic effects on beta cell function that can aid prevention and treatment of diabetes. cAMP is the primary mediator of these effects, and has been shown to potentiate glucose-stimulated insulin secretion, promote proper beta cells differentiation by increasing expression of the crucial transcription factor PDX-1, and prevent beta cell apoptosis. cGMP's role in beta cell function has received far less scrutiny, but there is emerging evidence that it may have a trophic impact on beta cell function analogous to that of cAMP.
35	16505238	Exposure of INS-1 beta-cells to elevated glucose leads to reduced insulin gene transcription, and this is associated with diminished binding of pancreatic duodenal homeobox factor 1 (PDX-1) and mammalian homologue of avian MafA/l-Maf (MafA).
36	16887799	We used DNA binding (gel shift) assays and Western immunoblots to demonstrate that cellular levels of the transcription factor PDX-1, normally decreased by glucotoxicity, were preserved with CDK5 inhibition, as was the binding of PDX-1 to the insulin promoter.
37	16968152	These nestin-positive cell-derived ICCs expressed numerous beta-cell lineage genes, including insulin; Glut-2; pancreatic duodenal homebox-1 protein (PDX-1); islet amyloid polypeptide (IAPP); neurogenin 3 (ngn3); and alpha, gamma, and delta cell gene markers.
38	17383157	Ectopic PDX-1 expression induced pancreatic gene expression and insulin production in the mice livers.
39	17457565	After transplantation, the PDX1-positive cells further differentiated into mature cell types producing insulin and glucagon, resulting in amelioration of hyperglycaemia and weight loss in streptozotocin-treated diabetic mice.
40	17416680	Although both groups on the high-fat diet developed insulin resistance, beta IRKO, but not beta IGFRKO, mice exhibited poor islet growth consistent with insulin-stimulated phosphorylation, nuclear exclusion of FoxO1, and reduced expression of Pdx-1.
41	17592437	Mutations in the IPF1 gene cause MODY4; IPF1 D76N is a polymorphism, which inhibits the insulin promoter and decreases insulin-secretion.
42	17784830	By day 34, Pdx1+ cells comprise between 5% and 20% of the total cell population and Insulin gene expression is up-regulated, with release of C-peptide into the culture medium.
43	17991720	Both peroxisome proliferator-activated receptor-alpha (PPARalpha) and pancreatic/duodenal homeobox-1 (PDX-1) have been reported to be associated with glucose-stimulated insulin secretion (GSIS), but the relationship between PPARalpha and PDX-1 is not yet fully understood.
44	17991720	In turn, this enhanced expression led to an increase in PDX-1 mRNA and nuclear protein, as well as DNA binding activity of PDX-1 with the insulin promoter.
45	17938503	In mature beta-cells, PDX-1 transactivates the insulin and other genes involved in glucose sensing and metabolism such as GLUT2 and glucokinase.
46	18468239	These data indicate that cell-surface heparan sulfate proteoglycans are required for PDX-1 internalization and that PDX-1 protein transduction could be a valuable strategy for inducing insulin expression in pancreatic stem/progenitor cells without requiring gene transfer technology.
47	18951876	In this study, human insulin promoter was activated by Smad2, Smad3 and the pancreatic and duodenal homeobox factor-1 (PDX-1) in the ALK7 pathway.
48	18951876	These results indicate that one of the direct target genes of Nodal and Activin AB signals is the insulin gene in pancreatic beta-cells and that PDX-1 is directly involved in the ALK7-Smad pathway.
49	18535489	At 6 wk of development (wd) insulin promoting factor 1 (IPF1) was expressed in the majority of epithelial cells forming tubular structures while GR was present in the mesenchyme, suggesting an early role of glucocorticoids, before endocrine and exocrine differentiation.
50	18535489	The first insulin cells did not express IPF1 or GR.
51	19371350	Combination treatment also increased expression of insulin and pancreatic and duodenal homeobox 1 (PDX1), maintained normal beta-cell/alpha-cell distribution in islets and restored pancreatic insulin content to levels comparable to non-diabetic mice.
52	19501121	The percentage of cells expressing Pdx-1 alone or together with INGAP or insulin increased significantly in ducts.
53	19576197	Thus, in mice, MafA expression in Pdx1+ pancreatic progenitors is not sufficient to specify insulin+ cells but in fact deters pancreatic development and the differentiation of endocrine cells.
54	19656489	Islet transduction with dominant-negative Pdx1 (RIPDN79PDX1) impairs mitochondrial metabolism and glucose-stimulated insulin secretion (GSIS).
55	15944145	This study was designed to assess whether palmitate alters the expression and binding activity of the key regulatory factors pancreas-duodenum homeobox-1 (PDX-1), MafA, and Beta2, which respectively bind to the A3, C1, and E1 elements in the proximal region of the insulin promoter.
56	15944145	Combined adenovirus-mediated overexpression of PDX-1 and MafA in islets completely prevented the inhibition of insulin gene expression by palmitate.
57	15944145	These results demonstrate that prolonged exposure of islets to palmitate inhibits insulin gene transcription by impairing nuclear localization of PDX-1 and cellular expression of MafA.
58	18199433	Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation.
59	18338074	In mature beta-cells, PDX-1 transactivates insulin and other beta-cell-related genes such as GLUT2 and glucokinase.
60	21108535	Indeed, the complementation of NKX6.1 by ectopic PDX-1 expression substantially and specifically promoted insulin expression and glucose regulated processed hormone secretion to a higher extent than that of PDX-1 alone, without increasing the reprogrammed cells.
61	20827659	The critical role of pdx-1 in stimulating certain endocrine pancreatic properties in RSCs was further confirmed upon the introduction of an expression construct for pdx-1 which markedly induced insulin and somatostatin.
62	20886041	Dispersed human pancreatic islets and MIN6 beta-cells were infected with a dual reporter lentivirus containing both eGFP driven by the insulin promoter and mRFP driven by the pdx1 promoter.
63	20886041	Using this approach and 5 replicate screens, we identified 7 extracts that reproducibly changed insulin and/or pdx1 promoter activity from a library of 1319 marine invertebrate extracts.
64	21190012	After infection with adenovirus expressing MAFA, Pdx1 or green fluorescent protein (Gfp), P2 rat islets were evaluated by RT-PCR and insulin secretion with static incubation and reverse haemolytic plaque assay (RHPA).
65	21190012	Overexpression of Pdx1 increased Mafa, Neurod1, glucokinase (Gck) mRNA and insulin content but failed to enhance glucose responsiveness.
66	20626638	The pancreatic duodenal homeobox-1 (PDX-1) expression might also be different because it links glucose metabolism to the regulation of insulin gene transcription in the pancreas. ?
67	21115832	Here, we identify 9cRA in mouse pancreas by liquid chromatography/tandem mass spectrometry (LC/MS/MS), and show that 9cRA decreases with feeding and after glucose dosing and varies inversely with serum insulin. 9cRA reduces glucose-stimulated insulin secretion (GSIS) in mouse islets and in the rat ?-cell line 832/13 within 15 min by reducing glucose transporter type 2 (Glut2) and glucokinase (GK) activities. 9cRA also reduces Pdx-1 and HNF4? mRNA expression, ?8- and 80-fold, respectively: defects in Pdx-1 or HNF4? cause maturity onset diabetes of the young (MODY4 and 1, respectively), as does a defective GK gene (MODY2).
68	20811152	These findings indicate that in adult mouse ? cells, Pcif1 limits Pdx1 protein accumulation and thus the expression of insulin and other gene targets important in the maintenance of ? cell mass and function.
69	8866550	In contrast to the insulin gene, however, neither the synergistic effect of the Pan1 expression on the IPF1-induced promoter activation nor the glucose responsiveness of the activity was observed for the GK gene promoter.
70	9000703	These data suggest that 1) the loss of GLUT2 protein associated with hyperglycemia is at least partially explained by reduced levels of the GLUT2 gene transcripts; 2) the reduction of beta-cell insulin content during chronic hyperglycemia may not be completely due to degranulation (reduced levels of gene transcripts may play a role); and 3) the reduction in the transcription factor IDX-1 raises the possibility that dysregulation of transcription factors may contribute to the abnormal beta-cell function found in states of chronic hyperglycemia.
71	9453241	The transcriptional control of the gene in beta-cells involves at least two islet-specific DNA-binding proteins, GTIIa and PDX-1, which also transactivates the insulin, somatostatin and glucokinase genes.
72	9460079	Notably, three MODY genes encode transcription factors implicated in the regulation of insulin gene transcription: hepatocyte nuclear factors 1 alpha and 4 alpha, and islet duodenum homeobox-1 (IDX-1, also known as IPF-1).
73	9604866	Since the STF-1, but not the RIPE-3b1 activator, gene has been cloned, we examined its restorative effects on insulin gene promoter activity after reconstitution with STF-1 cDNA.
74	9604866	Compared with basal levels, we observed a trend toward an increase in insulin promoter activity in intermediate passage cells with STF-1 transfection (1.43-fold) that became a significant increase when E2-5 was cotransfected (1.78-fold).
75	9604866	In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity.
76	9604866	Control studies in glucotoxic betaTC-6 cells deficient in RIPE-3b1 activator but not STF-1 did not demonstrate an increase in insulin promoter activity after STF-1 transfection.
77	9616224	Impaired functions of the transactivating factors islet duodenum homeobox-1 (IDX-1) and RIPE3b-binding proteins have been implicated in the pathological downregulation of insulin gene transcription by high glucose levels in pancreatic beta cell lines in vitro, and, similarly, the exposure of pancreatic islets to fatty acids decreases IDX-1 expression.
78	9616224	Our findings indicate that the differential dysregulation of both IDX-1 and C/EBPbeta, in response to sustained hyperglycemia or hyperlipidemia, may be involved in the impairment of insulin gene expression during the manifestation of diabetes mellitus.
79	9649577	This circumstance suggests that the mechanism of diabetes in these individuals may be due not only to reduced gene dosage, but also to a dominant negative inhibition of transcription of the insulin gene and other beta cell-specific genes regulated by the mutant IPF-1.
80	10078550	Islet duodenal homeobox 1 (IDX-1/PF-1/STF-1/PDX-1), a homeodomain protein that transactivates the insulin promoter, has been shown by targeted gene ablation to be required for pancreatic development.
81	10499550	The results of electrophoretic mobility shift experiments showed that PDX-1 protein binding to the Al element of the rat insulin II promoter was also increased 2 h post treatment with GLP-1.
82	10545531	Functional transactivation assays of these IPF-1 mutant isoforms in a beta-pancreatic tumor cell line transfected with a transcriptional reporter and IPF-1 expression plasmids demonstrate a significant inhibition of basal insulin promoter activity (stronger with the InsCCG243 mutant).
83	10567373	In addition, they exhibit impaired expression of the homeodomain transcription factor PDX1, which is a key component of the signaling pathway linking nutrient metabolism to the regulation of insulin gene expression.
84	10567702	PDX-1 has been suggested to be involved in the glucose-dependent regulation of insulin gene transcription.
85	10580420	To investigate if this sensitivity represents an acquired trait during beta-cell maturation, we used two in vitro cultured cell systems: 1) a pluripotent glucagon-positive pre-beta-cell phenotype (NHI-glu) that, after in vivo passage, matures into an insulin-producing beta-cell phenotype (NHI-ins) and 2) a glucagonoma cell-type (AN-glu) that, after stable transfection with pancreatic duodenal homeobox factor-1 (PDX-1), acquires the ability to produce insulin (AN-ins).
86	10720084	We conclude that variants in IPF-1 are not a common cause of MODY or late-onset type 2 diabetes in the Caucasian population, and that in terms of insulin transcription both the N76 and the T140 mutations are likely to represent functionally normal IPF-1 variants with no direct role in the pathogenesis of MODY or late-onset type 2 diabetes mellitus.
87	10868963	These effects are partially mediated through the activity of a homeodomain transcription factor, PDX-1, which binds to four sites within the human insulin gene promoter.
88	10868963	However, in NES2Y cells stably transfected with PDX-1 (NES-PDX-1), glucose exhibited a marked stimulatory effect on both the insulin promoter (5+/-0.2-fold, n = 6) and insulin mRNA levels (4.8+/-0.5-fold, n = 4).
89	10868963	These results demonstrate that glucose modulation of insulin mRNA levels is dependent on the activity of PDX-1 and that these effects are independent of changes in intracellular Ca2+ concentrations.
90	10905482	Here, we show that the insulinotropic hormone glucagon-like peptide (GLP)-1, which is produced by the intestine, enhances the pancreatic expression of the homeodomain transcription factor IDX-1 that is critical for pancreas development and the transcriptional regulation of the insulin gene.
91	10905482	Thus, in addition to stimulating insulin secretion, GLP-1 stimulates the expression of the transcription factor IDX-1 while stimulating beta-cell neogenesis and may thereby be an effective treatment for diabetes.
92	10909415	We demonstrated that PDX-1 is sufficient to activate the endogenous, otherwise silent, mouse insulin 1 and 2 and pro-insulin convertase gene expression in liver.
93	11316746	Furthermore, forskolin, (which stimulates adenylyl cyclase and insulin secretion), and 8-Bromo-cAMP, (an analog of cAMP which also stimulates insulin secretion), mimicked the effects of GLP-1 on PDX-1.
94	11457885	Mutations in the homeodomain transcription factor IDX-1, a critical regulator of pancreas development and insulin gene transcription, confer a strong predisposition to the development of diabetes mellitus in humans.
95	11457885	Doxycycline-induced impairment of IDX-1 expression reduced activation of the Insulin promoter but activated the Idx-1 promoter, suggesting that pancreatic beta cells regulate IDX-1 transcription to maintain IDX-1 levels within a narrow range.
96	11574405	Glucose and insulin regulate PDX-1 by way of a signaling pathway involving phosphatidylinositol 3-kinase (PI 3-kinase) and SAPK2/p38.
97	11574405	Glucose- and insulin-stimulated translocation of PDX-1 to the nucleoplasm was inhibited by wortmannin and SB 203580, indicating that a pathway involving PI 3-kinase and SAPK2/p38 was involved; translocation was unaffected by PD 098959 and rapamycin, suggesting that neither mitogen-activated protein kinase nor p70(s6k) were involved.
98	11574405	These results demonstrated that PDX-1 shuttles between the nuclear periphery and nucleoplasm in response to changes in glucose and insulin concentrations and that these events are dependent on PI 3-kinase, SAPK2/p38, and a nuclear phosphatase(s).
99	12099699	Pdx-1 is also able to bind and activate transcription from the A3 element of the human insulin gene promoter in yeast.
100	12124776	Differentiation to insulin-producing cells was also seen when Capan-1 cells were transfected with pdx-1, with 80% of these cells expressing insulin 3 days after transfection.
101	12145164	When the PDX-1(+) IEC-6 cells were kept in vitro, treatment with betacellulin could also confer insulin gene expression to them.
102	12150938	Glucose-regulated transcription of the insulin gene is in part mediated via the homeobox transcription factor PDX-1.
103	12503852	Glucose, the main physiological regulator of insulin secretion, also regulates insulin gene transcription through PDX-1.
104	12697734	Mice with 50% Pdx1, a homeobox gene critical for pancreatic development, had worsening glucose tolerance with age and reduced insulin release in response to glucose, KCl, and arginine from the perfused pancreas.
105	12697734	Surprisingly, insulin secretion in perifusion or static incubation experiments in response to glucose and other secretagogues was similar in islets isolated from Pdx1(+/-) mice compared with Pdx1(+/+) littermate controls.
106	12697734	These results suggest that an increase in apoptosis, with abnormal regulation of islet number and beta cell mass, represents a key mechanism whereby partial PDX1 deficiency leads to an organ-level defect in insulin secretion and diabetes.
107	12756298	We explored whether fetal human progenitor liver cells (FH) could be induced to differentiate into insulin-producing cells after expression of the pancreatic duodenal homeobox 1 (Pdx1) gene, which is a key regulator of pancreatic development and insulin expression in beta cells.
108	12756298	Immortalized FH cells expressing Pdx1 activated multiple beta-cell genes, produced and stored considerable amounts of insulin, and released insulin in a regulated manner in response to glucose.
109	12869553	We have also demonstrated the expression of upstream genes of Pdx-1, such as HNF3beta and HNF1alpha, as well as its downstream genes, including insulin, Glut2, and Nkx6.1, to be well preserved.
110	15047618	The results showed that pdx-1 expression clearly enhanced the expression of the insulin 2, somatostatin, Kir6.2, glucokinase, neurogenin3, p48, Pax6, PC2, and HNF6 genes in the resulting differentiated cells.
111	15047618	Thus, exogenous expression of pdx-1 should provide a promising approach for efficiently producing insulin-secreting cells from human ES cells for future therapeutic use in diabetic patients.
112	15331541	In vitro treatment of embryonic pancreata with dexamethasone, a glucocorticoid agonist, induced a decrease of insulin-expressing cell numbers and a doubling of acinar cell area, indicating that glucocorticoids favored acinar differentiation; in line with this, expression of Pdx-1, Pax-6, and Nkx6.1 was downregulated, whereas the mRNA levels of Ptf1-p48 and Hes-1 were increased.
113	15514704	As a possible mechanism underlying the phenomena, expression of pancreatic and duodenal homeobox factor-1 (PDX-1), an important transcription factor for the insulin gene, was more clearly visible in the nuclei of islet cells after the antioxidant treatment.
114	15664997	In this study, we show that MafA overexpression, together with PDX-1 (pancreatic and duodenal homeobox factor-1) and NeuroD, markedly increases insulin gene expression in the liver.
115	15677506	Similarly, Ex-4 failed to increase levels of plasma insulin, pancreatic insulin content, and pancreatic insulin mRNA transcripts in beta-cell(Pdx1-/-) mice.
116	15677506	Moreover, Ex-4 increased the levels of insulin and amylin mRNA transcripts and augmented glucose-stimulated insulin secretion in islets from beta-cell(Pdx1+/+) mice but not in beta-cell(Pdx1-/-) islets.
117	15793239	In this study, we showed that a modified form of the pancreatic and duodenal homeobox factor 1 (PDX-1) carrying the VP16 transcriptional activation domain (PDX-1/VP16) markedly increases insulin biosynthesis and induces various pancreas-related factors in the liver, especially in the presence of NeuroD or neurogenin 3 (Ngn3).
118	15793239	Thus PDX-1/VP16 expression, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance.
119	15896300	We previously reported that exogenous PDX-1 protein can permeate cells and induce insulin gene expression in progenitor cells.
120	15899968	PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner.
121	15935394	The release of insulin, the expression of preproinsulin (PPI), glucose transporter2 (GLUT2) and pancreatic duodenal homeobox-1 (PDX-1), and levels of intracellular free Ca++([Ca++]i) were measured in rat pancreatic islets treated with or without high concentrations of FFA (0.1 and 1.0 mM oleic acid) for 24 h.
122	16055439	Insulin gene expression is regulated by pancreatic beta cell-specific factors, PDX-1 and BETA2/E47.
123	16504534	A more promising gene therapy approach has been to express pancreatic endocrine developmental factors, such as PDX-1, NeuroD/BETA2 and Neurogenin 3, to promote differentiation of non-endocrine cells towards a beta cell or islet phenotype, enabling these cells to synthesize and secrete insulin in a glucose-regulated manner.
124	16543365	Notably, augmenting Egr-1 expression levels in insulin-producing cells increased the mRNA and protein expression levels of pancreas duodenum homeobox-1 (PDX-1), a major transcriptional regulator of glucose-responsive activation of the insulin gene.
125	16543365	Increasing Egr-1 expression levels enhanced PDX-1 binding to insulin promoter sequences, whereas mutagenesis of PDX-1-binding sites reduced the capacity of Egr-1 to activate the insulin promoter.
126	16936209	RNA of Pdx-1, Glut-2, and Gck was detectable by RT-PCR in whole thymus but not in the clones, suggesting thymic proinsulin expression is Pdx-1 independent and that Pdx-1, Glut-2, and Gck are likely expressed in the thymus as antigens, not as regulatory molecules.
127	17150967	Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia.
128	17158802	Insulin treatment was associated with the nuclear localization of Pdx1 and the prosurvival effects of insulin were largely absent in islets 50% deficient in Pdx1, providing direct evidence that Pdx1 is a signaling target of insulin.
129	17158802	Bridge-1, a Pdx1-binding partner and regulator of beta-cell survival, was increased significantly at low insulin doses.
130	17226789	The differentiated PDX-1+ hMSCs expressed multiple islet-cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C-peptide in a weak glucose-regulated manner.
131	17259388	SHP downregulates insulin gene expression via two mechanisms: by downregulating PDX-1 and MafA gene expression and by inhibiting p300-mediated pancreatic duodenal homeobox factor 1-and BETA2-dependent transcriptional activity from the insulin promoter.
132	17299998	Infection with the adenovirus expressing PDX-1, Ngn3, NeuroD, or Pax4 induced the insulin gene expression.
133	17449132	Furthermore, MafA markedly enhances insulin gene promoter activity and ameliorates glucose tolerance in diabetic mice, especially in the presence of PDX-1 and NeuroD.
134	17467845	In conclusion, with increasing age, insulin secretory function of islets deteriorates accompanied with a decrease in expression of beta cell-specific genes including PDX-1.
135	17627512	In mature beta-cells, PDX-1 transactivates the insulin gene and other genes involved in glucose sensing and metabolism, such as GLUT2 and glucokinase.
136	17706592	Insulin promoter assay showed that Pdx1 highly activates insulin promoter when combined with Ngn3.
137	17709883	The molecular mechanisms responsible for the glucose toxic effect on beta cell function involves disappearance of two important regulators of insulin promoter activity, PDX-1 and MafA.
138	17785922	It is produced exclusively by pancreatic islet beta-cells. beta-cell-enriched transcription factors, such as Pdx1 and Beta2, have dual roles in the activation of the insulin gene promoter establishing beta-cell-specific insulin expression, and in the regulation of beta-cell differentiation.
139	17900743	Thus, our study demonstrated that pdx-1 is not essential for insulin gene expression, at least in cells differentiated from this population of nestin-expression enriched ES cells, and suggested that the insulin-producing cells derived from ES cells may be different from the pancreatic beta cells in terms of their lineage.
140	17991758	Prolonged exposure of isolated islets of Langerhans to elevated levels of fatty acids, in the presence of high glucose, impairs insulin gene expression via a transcriptional mechanism involving nuclear exclusion of pancreas-duodenum homeobox-1 (Pdx-1) and loss of MafA expression.
141	17991758	This was associated with reduced Pdx-1 binding to the endogenous insulin promoter, and an increased proportion of Pdx-1 localized in the cytoplasm versus the nucleus.
142	18360684	PDX-1 binds to the promoter of insulin, glucose transporter 2, and glucokinase and regulates their expression.
143	18360684	By protein-protein interaction, PDX-1 acts in concert with other transcription factors or coactivators at the level of the insulin promoter.
144	19062254	Interestingly, immunohistochemistry demonstrated that, the islets from MSC-treated rats expressed high levels of PDX-1 and that these cells were also positive for insulin staining.
145	19393272	Furthermore, MafA overexpression, together with PDX-1 and NeuroD, markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells.
146	19604517	Gestational high-fat programming impairs insulin release and reduces Pdx-1 and GK immunoreactivity.
147	19689288	The combination of MafA, PDX-1 and NeuroD markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells.
148	19757377	While stable expression of Pdx1 in ASCs did not induce the pancreatic phenotype in vitro in our experiment, the transplanted stem cells became engrafted in the pancreas, wherein they expressed insulin and C-peptide, which is a marker of insulin-producing cells.
149	19785038	We explored this possibility by determining whether ectopic expression of transcription factors known to induce transcription of this gene in beta cells, pancreatic and duodenal homeobox factor 1 (Pdx1), V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa), and neurogenic differentiation 1 (Neurod1), would activate INS gene expression in long-term hIPC cultures.
150	19785038	In contrast to the endogenous promoter, an exogenous rat INS promoter was activated by expression of Pdx1 and Mafa in hIPCs.
151	19785038	Lastly, ChIP assays show that exogenously expressed Pdx1 and Mafa bind at very low levels to the INS promoter and at 20- to 25-fold higher levels to the GCG promoter in hIPCs.
152	19855005	Here, we find that Pdx1 is required for compensatory beta cell mass expansion in response to diet-induced insulin resistance through its roles in promoting beta cell survival and compensatory hypertrophy.
153	19855005	These findings suggest that Pdx1 deficiency leads to a failure of beta cell compensation for insulin resistance at least in part by impairing critical functions of the ER.
154	19901909	Pancreatic duodenal homeobox 1 (Pdx1) protein is a key transcription factor involved in the regulation of insulin gene expression that is expressed at high levels in the beta-cells of the pancreatic islets.
155	20349222	Surprisingly, XBP1s overexpression impaired glucose-stimulated insulin secretion and increased beta cell apoptosis, whereas it protected fibroblasts against cell death induced by ER-stress. mRNA expression of Pdx1 and Mafa was inhibited in cells overproducing XBP1s, leading to decreased insulin expression.
156	20349222	XBP1s knockdown partially restored cytokine/ER-stress-driven insulin and Pdx1 inhibition but had no effect on cytokine-induced ER-stress and apoptosis.
157	21799688	This effect may possibly be involved in enhancing beta-cell regeneration and promoting insulin secretion by targeting PPAR? and PDX-1.
158	21540283	Pancreatic and duodenal homeobox 1 (PDX1), a key pancreatic transcription factor, regulates insulin along with targets involved in insulin processing and secretion.
159	21506889	Transgenic overexpression of NGN3 and/or PDX1 proteins not only induced direct target genes, such as NEUROD1 and insulin, and but also triggered parts of the gene expression cascade that is involved in pancreatic endocrine differentiation.
160	21765243	Moreover, hPL-A induced PDX-1 intracellular expression, improving beta cell activity and ameliorating insulin secretion in response to high glucose stimulation.