scholarly journals Glucagon-like peptide-1 stimulates human insulin promoter activity in part through cAMP-responsive elements that lie upstream and downstream of the transcription start site

2005 ◽  
Vol 186 (2) ◽  
pp. 353-365 ◽  
Author(s):  
Colin W Hay ◽  
Elaine M Sinclair ◽  
Giovanna Bermano ◽  
Elaine Durward ◽  
Mohammad Tadayyon ◽  
...  
Keyword(s):  
Protein Binding ◽  
Human Insulin ◽  
Insulin Gene ◽  
Start Site ◽  
Β Cells ◽  
Transcription Start ◽  
Pancreatic Β Cells ◽  
Insulin Promoter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted from the enteroendocrine L-cells of the gut and which acts primarily to potentiate the effects of glucose on insulin secretion from pancreatic β-cells. It also stimulates insulin gene expression, proinsulin biosynthesis and affects the growth and differentiation of the islets of Langerhans. Previous studies on the mechanisms whereby GLP-1 regulates insulin gene transcription have focused on the rat insulin promoter. The aim of this study was to determine whether the human insulin promoter was also responsive to GLP-1, and if so to investigate the possible role of cAMP-responsive elements (CREs) that lie upstream (CRE1 and CRE2) and downstream (CRE3 and CRE4) of the transcription start site. INS-1 pancreatic β-cells were transfected with promoter constructs containing fragments of the insulin gene promoter placed upstream of the firefly luciferase reporter gene. GLP-1 was found to stimulate the human insulin promoter, albeit to a lesser degree than the rat insulin promoter. Mutagenesis of CRE2, CRE3 and CRE4 blocked the stimulatory effect of GLP-1 while mutagenesis of CRE1 had no effect. Analysis of nuclear protein binding to the four CREs showed that, while they share some proteins, each CRE site is unique. Stimulation of transcription by GLP-1 through CRE2, CRE3 and CRE4 resulted in altered protein binding that was different for each of the CRE sites involved. Collectively, these data show that the four human CREs are not simply multiple copies of the rat CRE site and further emphasise that the human insulin promoter is distinct from the rodent promoter.

scholarly journals Regulation of Insulin Gene Transcription by the Immediate-Early Growth Response Gene Egr-1

Endocrinology ◽  
2006 ◽  
Vol 147 (6) ◽  
pp. 2923-2935 ◽  
Author(s):  
Kazuhiro Eto ◽  
Varinderpal Kaur ◽  
Melissa K. Thomas
Keyword(s):  
Transcriptional Activation ◽  
Growth Response ◽  
Insulin Gene ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Expression Levels ◽  
Promoter Sequences ◽  
Early Growth Response ◽  
Insulin Promoter ◽  
Insulin Gene Expression

Abstract Changes in extracellular glucose levels regulate the expression of the immediate-early response gene and zinc finger transcription factor early growth response-1 (Egr-1) in insulin-producing pancreatic β-cells, but key target genes of Egr-1 in the endocrine pancreas have not been identified. We found that overexpression of Egr-1 in clonal (INS-1) β-cells increased transcriptional activation of the rat insulin I promoter. In contrast, reductions in Egr-1 expression levels or function with the introduction of either small interfering RNA targeted to Egr-1 (siEgr-1) or a dominant-negative form of Egr-1 decreased insulin promoter activation, and siEgr-1 suppressed insulin gene expression. Egr-1 did not directly interact with insulin promoter sequences, and mutagenesis of a potential G box recognition sequence for Egr-1 did not impair the Egr-1 responsiveness of the insulin promoter, suggesting that regulation of insulin gene expression by Egr-1 is probably mediated through additional transcription factors. Overexpression of Egr-1 increased, and reduction of Egr-1 expression decreased, transcriptional activation of the glucose-responsive FarFlat minienhancer within the rat insulin I promoter despite the absence of demonstrable Egr-1-binding activity to FarFlat sequences. 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. 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. We propose that changes in Egr-1 expression levels in response to extracellular signals, including glucose, can regulate PDX-1 expression and insulin production in pancreatic β-cells.

scholarly journals Glucagon-Like Peptide-1 Agonists Protect Pancreatic β-Cells From Lipotoxic Endoplasmic Reticulum Stress Through Upregulation of BiP and JunB

Diabetes ◽  
2009 ◽  
Vol 58 (12) ◽  
pp. 2851-2862 ◽  
Author(s):  
Daniel A. Cunha ◽  
Laurence Ladrière ◽  
Fernanda Ortis ◽  
Mariana Igoillo-Esteve ◽  
Esteban N. Gurzov ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Glucagon-Like Peptide 1 Protects Pancreatic β-Cells From Death by Increasing Autophagic Flux and Restoring Lysosomal Function

Diabetes ◽  
2017 ◽  
Vol 66 (5) ◽  
pp. 1272-1285 ◽  
Author(s):  
Francesco P. Zummo ◽  
Kirsty S. Cullen ◽  
Minna Honkanen-Scott ◽  
James A.M. Shaw ◽  
Penny E. Lovat ◽  
...  
Keyword(s):  
Autophagic Flux ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Lysosomal Function ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Induction of miR-132 and miR-212 Expression by Glucagon-Like Peptide 1 (GLP-1) in Rodent and Human Pancreatic β-Cells

2015 ◽  
Vol 29 (9) ◽  
pp. 1243-1253 ◽  
Author(s):  
Jin Shang ◽  
Jing Li ◽  
Mark P. Keller ◽  
Hans E. Hohmeier ◽  
Yong Wang ◽  
...  
Keyword(s):  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Molecular physiology of glucagon-like peptide-1 insulin secretagogue action in pancreatic β cells

2011 ◽  
Vol 107 (2) ◽  
pp. 236-247 ◽  
Author(s):  
Colin A. Leech ◽  
Igor Dzhura ◽  
Oleg G. Chepurny ◽  
Guoxin Kang ◽  
Frank Schwede ◽  
...  
Keyword(s):  
Β Cells ◽  
Pancreatic Β Cells ◽  
Molecular Physiology ◽  
Insulin Secretagogue ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
Sign in / Sign up

Export Citation Format

Share Document