ArticleThe EMBO journal2006
ICER induced by hyperglycemia represses the expression of genes essential for insulin exocytosis.
Article in The EMBO journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 66 citations in OpenAlex.
- Novel Aspects of cAMP-Response Element Modulator (CREM) Role in Spermatogenesis and Male Fertility.International journal of molecular sciences · 2023Review
- Article
- In vivo Roles of Rab27 and Its Effectors in Exocytosis.Cell structure and function · 2021Review
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Bridging the Gap Between Diabetes and Stroke in Search of High Clinical Relevance Therapeutic Targets.Neuromolecular medicine · 2019Review
- Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity.Journal of diabetes research · 2016Article
- ERK5 activation in macrophages promotes efferocytosis and inhibits atherosclerosis.Circulation · 2014Article
- JNK3 is required for the cytoprotective effect of exendin 4.Journal of diabetes research · 2014Article
- Decompensation of β-cells in diabetes: when pancreatic β-cells are on ICE(R).Journal of diabetes research · 2014Review
- Article
- Reduction of connexin36 content by ICER-1 contributes to insulin-secreting cells apoptosis induced by oxidized LDL particles.PloS one · 2013Article
- Modulation of neuronal pentraxin 1 expression in rat pancreatic β-cells submitted to chronic glucotoxic stress.Molecular & cellular proteomics : MCP · 2012Article
- Evidence for tuning adipocytes ICER levels for obesity care.Adipocyte · 2012Article
- Regulation of microRNA-375 by cAMP in pancreatic β-cells.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Deregulation of CREB signaling pathway induced by chronic hyperglycemia downregulates NeuroD transcription.PloS one · 2012Article
- Impaired expression of the inducible cAMP early repressor accounts for sustained adipose CREB activity in obesity.Diabetes · 2011Article
- Role for inducible cAMP early repressor in promoting pancreatic beta cell dysfunction evoked by oxidative stress in human and rat islets.Diabetologia · 2011Article
- Adenylyl cyclase 8 is central to glucagon-like peptide 1 signalling and effects of chronically elevated glucose in rat and human pancreatic beta cells.Diabetologia · 2011Article
- Roles of myosin Va and Rab3D in membrane remodeling of immature secretory granules.Cellular and molecular neurobiology · 2010Article
- In vitro expression of NGN3 identifies RAB3B as the predominant Ras-associated GTP-binding protein 3 family member in human islets.The Journal of endocrinology · 2010Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The GTPases Rab3a and Rab27a and their effectors Granuphilin/Slp4 and Noc2 are essential regulators of neuroendocrine secretion. Chronic exposure of pancreatic beta-cells to supraphysiological glucose levels decreased selectively the expression of these proteins. This glucotoxic effect was mimicked by cAMP-raising agents and blocked by PKA inhibitors. We demonstrate that the transcriptional repressor ICER, which is induced in a PKA-dependent manner by chronic hyperglycemia and cAMP-raising agents, is responsible for the decline of the four genes. ICER overexpression diminished the level of Granuphilin, Noc2, Rab3a and Rab27a by binding to cAMP responsive elements located in the promoters of these genes and inhibited exocytosis of beta-cells in response to secretagogues. Moreover, the loss in the expression of the genes of the secretory machinery caused by glucose and cAMP-raising agents was prevented by an antisense construct that reduces ICER levels. We propose that induction of inappropriate ICER levels lead to defects in the secretory process of pancreatic beta-cells possibly contributing, in conjunction with other known deleterious effects of hyperglycemia, to defective insulin release in type 2 diabetes.
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