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INS — PDX1

Pathways - manually collected, often from reviews:

• KEGG Type II diabetes mellitus: PDX1 → INS (gene expression, expression)

Text-mined interactions from Literome

Seijffers et al., Endocrinology 1999 (Insulinoma) : PDX-1 overexpression did not reduce E47 and BETA2 levels, but was sufficient to suppress rat insulin promoter activity in a dose dependent manner ... Our data demonstrate that PDX-1 regulates transcription of the insulin gene in a dose dependent manner
Shushan et al., DNA Cell Biol 1999 : The pancreatic and duodenal homeobox-1 ( PDX-1 ) plays a major role in glucose induced insulin transcription
Qian et al., Biochem J 1999 : Importantly, the lower Pdx-1 protein levels led to a greater than 50 % reduction in Pdx-1 binding activity to the A3 element on the insulin gene promoter, and a significant reduction in insulin mRNA levels
Furukawa et al., Endocr J 1999 : In this study, we tried to elucidate the role of PDX-1 in the glucose induced transcriptional activation of the human insulin gene promoter in MIN6 cells
Macfarlane et al., J Clin Invest 1999 (Diabetes Mellitus, Type 2...) : The transcription factor insulin promoter factor-1 (IPF-1) plays a central role in both the development of the pancreas and the regulation of insulin gene expression in the mature pancreatic beta cell
Wu et al., Biochem J 1999 : Insulin was shown to potently activate PDX1 DNA binding activity and insulin promoter activity ... These results suggest that both glucose and insulin stimulate PDX1 DNA binding activity and insulin promoter activity via a pathway involving PtdIns 3-kinase and SAPK2
Glick et al., J Biol Chem 2000 : Separate expression of BETA2, E2A, or PDX1 led to modest ( < 10-fold ) activation of the insulin promoter, whereas co-expression of the three proteins produced synergistic, high level activation ( 160-fold )
Macfarlane et al., J Biol Chem 2000 : We have previously used these cells to show that glucose regulation of the insulin gene is dependent on PDX1 , but not calcium
Ferber et al., Nat Med 2000 (Hyperglycemia) : PDX-1 regulates insulin gene expression and is involved in islet cell-specific expression of various genes ... Expression of PDX-1 resulted in a substantial increase in hepatic immunoreactive insulin content and an increase of 300 % in plasma immunoreactive insulin levels, compared with that in mice treated with control adenovirus ... Hepatic immunoreactive insulin induced by PDX-1 was processed to mature mouse insulin 1 and 2 and was biologically active ; it ameliorated hyperglycemia in diabetic mice treated with streptozotocin
Macfarlane et al., Diabetes 2000 (Pancreatic Diseases) : Glucose modulation of insulin mRNA levels is dependent on transcription factor PDX-1 and occurs independently of changes in intracellular Ca2+ ... The availability of a human beta-like cell line, NES2Y, which lacks PDX-1 but expresses the insulin gene, allowed us to determine whether PDX-1 was essential for the stimulatory effect of glucose on insulin mRNA levels ... 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
Ferber et al., Isr Med Assoc J 2000 (Diabetes Mellitus, Type 1...) : 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 ... PDX-1 expression in liver resulted in a 25-fold increase in hepatic immunoreactive insulin content and a threefold increase in plasma immunoreactive insulin levels, as compared to control adenovirus treated mice ... Hepatic immunoreactive insulin , induced by PDX-1 , was processed to mature mI-1 and mI-2 and was biologically active ; it ameliorated hyperglycemia in streptozotocin treated diabetic mice
Clocquet et al., Diabetes 2000 (Diabetes Mellitus, Type 2) : IPF-1 is required for the development of the pancreas and mediates glucose-responsive stimulation of insulin gene transcription
Peshavaria et al., Mol Endocrinol 2000 : This study focuses on the mechanisms by which PDX-1 activates insulin gene transcription ... To evaluate the role of PDX-1 in transcription of the insulin gene, a chloramphenicol acetyltransferase reporter construct was designed with a single yeast GAL4-DNA binding site in place of the A3/PDX-1 binding element in the rat insulin II enhancer
Thomas et al., Endocrinology 2001 : Because IDX-1 gene expression is essential for insulin gene expression, pancreatic beta-cell development, and normal glucose homeostasis, our findings that Hh signaling regulates IDX-1 expression in the endocrine pancreas suggest possible novel therapeutic approaches for diabetes mellitus
Yamakawa et al., Endocr Res 2001 : The present data indicate that IPF1 rather than HNF-1alpha predominantly transactivates the insulin gene, and that HNF-1alpha inhibits IPF1 dependent insulin gene transactivation mediated through the 5 ' flanking sequence of the A3 element
Leibowitz et al., Diabetes 2001 (Diabetes Mellitus, Type 2...) : The homeodomain transcription factor IPF1/PDX1 is required in beta-cells for efficient expression of insulin , glucose transporter 2, and prohormone convertases 1/3 and 2
Shinozuka et al., Biochem Biophys Res Commun 2001 : Altered expression of HES-1, BETA2/NeuroD, and PDX-1 is involved in impaired insulin synthesis induced by glucocorticoids in HIT-T15 cells
Elrick et al., Diabetes 2001 : Glucose and insulin regulate PDX-1 by way of a signaling pathway involving phosphatidylinositol 3-kinase ( PI 3-kinase ) and SAPK2/p38 ... 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
Qiu et al., Mol Cell Biol 2002 : Insulin gene transcription is mediated by interactions between the p300 coactivator and PDX-1 , BETA2, and E47
Kaneto et al., J Biol Chem 2002 : In HeLa and HepG2 cells c-Myc exerted a suppressive effect on the insulin promoter activity only in the presence of NeuroD/BETA2 but not PDX-1
Kojima et al., Diabetes 2002 : These results indicated that combined expression of Pdx-1 and Isl-1 in IEC-6 cells was required for the production of insulin
Campbell et al., Biochem Biophys Res Commun 2002 : The current study has established the fact that glucose, GLP-1, insulin , T ( 3 ), HB-EGF, and TNF-alpha all positively regulate the PDX1 gene promoter in pancreatic beta-cells
Johnson et al., J Clin Invest 2003 (Calcium Signaling) : 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
Miyazaki et al., Diabetes 2004 : 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
Nakajima-Nagata et al., Biochem Biophys Res Commun 2004 : In addition, enforced expression of the homeodomain transcription factor Pdx1 in these cells contributes to enhancement of insulin release in response to insulin secretagogues
Nakajima-Nagata et al., Biochem Biophys Res Commun 2004 : However, the role of Pdx-1 in the regulation of insulin release is not well established ... We further demonstrated the essential role of Pdx-1 in insulin secretion by the gene knock-down strategy ... Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus
Mosley et al., Mol Endocrinol 2004 : Disruption of the function of the endogenous Pdx-1 abolishes the recruitment of p300 to the insulin gene promoter at high concentrations of glucose and results in decreased histone H4 acetylation and insulin gene expression
Imai et al., Biochem Biophys Res Commun 2005 (Diabetes Mellitus) : Constitutively active PDX1 induced efficient insulin production in adult murine liver ... Thus, transient expression of an active mutant of PDX1 in the liver induced sustained PDX1 and insulin expressions without loss of hepatocytic function
Harmon et al., J Biol Chem 2005 : Additionally, transient transfection of PDX-1 or MafA cDNA into glucotoxic cells increased PDX-1 and MafA protein levels and individually increased insulin promoter activity ( untreated = 34 %, PDX-1 = 70 %, MafA = 78 % ; percentage of activity of early passage cells ), whereas the combined transfection of MafA and PDX-1 completely restored insulin promoter activity
Zhao et al., J Biol Chem 2005 : The islet enriched MafA, PDX-1 , and BETA2 activators contribute to both beta cell-specific and glucose-responsive insulin gene transcription
Iype et al., J Biol Chem 2005 : To determine the mechanism underlying regulation of the insulin gene by Pdx-1 , we performed a kinetic analysis of insulin transcription following adenovirus mediated delivery of a small interfering RNA specific for pdx-1 into insulinoma cells and pancreatic islets to diminish endogenous Pdx-1 protein ... Our results suggest that Pdx-1 directly regulates insulin transcription through formation of a complex with transcriptional coactivators on the proximal insulin promoter
Wang et al., Diabetologia 2005 (Calcium Signaling) : Induction of DN-Pdx-1 resulted in defective glucose stimulated and K+-depolarisation induced insulin secretion in INS-1 cells, while overexpression of Pdx-1 had no effect
Kaneto et al., Diabetes 2005 (Carcinoma, Hepatocellular...) : Thus PDX-1/VP16 expression, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance
Docherty et al., Biochem J 2005 : PDX-1 was shown further to activate the endogenous insulin 1 gene in alphaTC1.6 cells, whereas MafA activated the insulin 2 gene ... In combination, PDX-1 and MafA activated both insulin genes
Stanojevic et al., Mol Cell Endocrinol 2005 : Transcriptional activation by PDX-1 is increased by addition of Bridge-1 in multiple contexts, including synergistic activation of a Gal4 reporter by Gal4-Bridge-1 and Gal4-PDX-1 fusion proteins, activation of the somatostatin promoter TAAT1 enhancer, and synergistic activation of the rat insulin I promoter FarFlat enhancer by PDX-1 , E12, and E47
Hagman et al., J Biol Chem 2005 : Combined adenovirus mediated overexpression of PDX-1 and MafA in islets completely prevented the inhibition of insulin gene expression by palmitate ... 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
Kwon et al., Mol Ther 2005 : The transduced TAT-PDX1 activated its downstream target genes and induced insulin protein production in hESCs
Amemiya-Kudo et al., J Biol Chem 2005 : Insulin gene expression is regulated by pancreatic beta cell-specific factors, PDX-1 and BETA2/E47
Holland et al., Diabetes 2005 (Diabetes Mellitus, Experimental) : Repression of Pdx1 in adult mice impaired expression of insulin and glucagon, leading to diabetes within 14 days
Le Lay et al., J Endocrinol 2006 : Involvement of PDX-1 in activation of human insulin gene transcription
Eto et al., Endocrinology 2006 : 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
Koizumi et al., Surgery 2006 (Hyperglycemia) : Forced expression of PDX-1 induces insulin production in intestinal epithelia ... Recently, ectopic expression of pdx-1 in the liver successfully induced insulin production and ameliorated hyperglycemia
Yamada et al., Endocr J 2006 : In this condition, transfer of PDX-1/VP16 also induced the expression of insulin
Liu et al., J Surg Res 2007 (Carcinoma, Pancreatic Ductal...) : Thus, these results also indicated that PDX-1 plays critical roles in insulin promoter activation and demonstrated that PDX-1 production is essential for insulin promoter directed gene therapy
Wang et al., Pancreas 2007 (Pancreatic Neoplasms) : Overexpression of Ad-Pdx-1 in alpha-TC-1 cells induced insulin gene expression ... Collectively, these experiments revealed that Pdx-1 is a potent transcriptional regulator that is capable of modulating histone H4 acetylation and activates the insulin gene in a terminally differentiated glucagonoma cell line
Shternhall-Ron et al., J Autoimmun 2007 (Diabetes Mellitus, Type 1) : Ectopic PDX-1 expression induced pancreatic gene expression and insulin production in the mice livers
Okada et al., Proc Natl Acad Sci U S A 2007 (Hyperplasia...) : 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
Feanny et al., J Surg Res 2008 : Transcription factor pancreatic duodenal homeobox-1 (PDX-1) is critical for beta-cell differentiation and insulin gene expression
Yoon et al., Biochem Biophys Res Commun 2007 (Diabetes Mellitus) : Insulin promoter assay showed that Pdx1 highly activates insulin promoter when combined with Ngn3
Takayama et al., Diabetes Res Clin Pract 2008 : 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
Muniappan et al., BMC physiology 2007 : Expression of either human insulin or the beta cell specific transcription factors PDX-1 , NeuroD1 and MafA in the Hepa1-6 cell line or primary liver cells via adenoviral gene transfer, results in production and secretion of insulin
Rosanas-Urgell et al., International journal of biological sciences 2008 : The crucial role of PDX1 in pancreas development, beta-cell formation and insulin transcription regulation has long been established
Jonmarker et al., APMIS 2008 (Neoplasm Metastasis...) : Pancreatic duodenal homeobox 1 (PDX-1) , a Hox type transcription factor, is necessary for differentiation of exocrine and endocrine pancreas, and regulates insulin gene transcription
Boucher et al., Endocrinology 2009 : Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased insulin expression and secretion
Pillich et al., Molecules (Basel, Switzerland) 2008 : Previous studies have indicated that ectopic Pdx-1 expression in liver or intestinal primary and immortalized cells is sufficient to promote activation of insulin gene expression
Nagaya et al., J Endocrinol 2009 : Transduced expression of PDX-1, NEUROD or PDX-1/VP16 led to expression of not only INS but also GLUT2 and prohormone convertase 1 and 2
Gauthier et al., Cell Metab 2009 : PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression
Wilson et al., Stem Cells 2009 : In contrast to the endogenous promoter, an exogenous rat INS promoter was activated by expression of Pdx1 and Mafa in hIPCs
You et al., Endocrinology 2009 : Pancreas duodenum homeobox-1 (PDX-1) is essential for pancreas development, insulin production, and glucose homeostasis, and ANP increased PDX-1 mRNA levels by 2- to 3-fold in INS-1E cells and islets
Liu et al., Sheng Li Xue Bao 2010 : Moreover, we found that GCK protein level was significantly reduced by UII, while PDX-1 , a key regulator of insulin gene transcription in beta cells, was not affected
Kwon et al., Nutrition 2011 : This improvement was associated with insulin/insulin-like growth factor-1 signaling that was activated by the tyrosine phosphorylation of insulin receptor substrate-2 and serine phosphorylation of Akt, and this in turn increased pancreatic and duodenal homeobox-1 expression
Ardestani et al., J Biol Chem 2011 (Diabetes Mellitus) : The transcription factor PDX1 plays a critical role during ß-cell development and in glucose induced insulin gene transcription in adult ß-cells
You et al., Diabetes & metabolism journal 2011 : The adenovirus mediated overexpression of PDX-1 , BETA2/NeuroD and MafA induced insulin gene expression in NPCCs, but not in adult pig pancreatic cells
Zhang et al., J Cell Physiol 2012 : Ectopic expression of INSM1 directly induces insulin , Pax6, and Nkx6.1 expression, whereas Pdx-1 and NeuroD1 were slightly suppressed by INSM1
Takemitsu et al., Res Vet Sci 2012 : Our results confirm that similar to humans, Pdx1 plays an important role in expression of insulin gene in canines
Zanini et al., PloS one 2011 : PDX1 ( pancreatic duodenal homeobox gene-1 ), insulin, C peptide and Glut-2 were detected in HI-ILCs whereas BM-ILCs only expressed Glut-2 and insulin
Lee et al., Cell Transplant 2013 : Insulin transcript levels and the expression of key transcription factors required for pancreatic development including FoxA2, Nkx2.2, and NeuroD were significantly increased by exogenous Pdx-1 overexpression
Danso-Abeam et al., Eur J Immunol 2013 : Surprisingly, we found that lack of Pdx1 in TECs did not reduce the transcription of insulin or somatostatin, or alter glucagon expression
Katz et al., Stem Cells Dev 2013 : Overexpression of Pdx1 , a TF important for islet differentiation, and silencing of musculoaponeurotic fibrosarcoma oncogene homolog B, a TF that is expressed in mature glucagon producing cells, result in induction of insulin to a higher level compared to Romi and 5-AzC alone
Ohlsson et al., EMBO J 1993 : The pattern of IPF1 expression and its ability to stimulate insulin gene transcription suggest that IPF1 functions both in the regionalization of the primitive gut endoderm and in the maturation of the pancreatic beta-cell
Petersen et al., Proc Natl Acad Sci U S A 1994 (Insulinoma...) : Transcriptional regulation of the human insulin gene is dependent on the homeodomain protein STF1/IPF1 acting through the CT boxes
Dumonteil et al., Diabetes Metab 1996 : Remarkably, IPF-1 and IEF1 are involved in both beta-cell-specific expression and glucose regulation of the insulin gene
Marshak et al., Proc Natl Acad Sci U S A 1996 (Insulinoma...) : A single mutation in the GSF binding site of the human insulin promoter abolishes the stimulation by high glucose only in normal islets, supporting the suggested physiological role of GSF in the glucose regulated expression of the insulin gene ... It is demonstrated that high levels of ectopic GSF/IPF-1 inhibit the expression of the human insulin gene in normal islets, but not in transformed beta TC1 cells
Argenton et al., FEBS Lett 1997 : The conserved role of PDX1 in vertebrate insulin gene regulation opens the possibility to exploit fish models in the study of pancreas development
Peshavaria et al., Mol Cell Biol 1997 : These sequences were also required by PDX-1 to synergistically activate insulin enhancer mediated transcription with another key insulin gene activator, the E2A encoded basic helix-loop-helix E2-5 and E47 proteins ... These results suggest that PDX-1 is not absolutely essential for insulin gene expression in betaTC3 cells