ArticleBMC molecular biology2007
Transcriptional response of pancreatic beta cells to metabolic stimulation: large scale identification of immediate-early and secondary response genes.
Article in BMC molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 63 citations in OpenAlex.
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- Single-cell transcriptomic profiling of human pancreatic islets reveals genes responsive to glucose exposure over 24 h.Diabetologia · 2024Article
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- Single cell multiomic analysis reveals diabetes-associated β-cell heterogeneity driven by HNF1A.Nature communications · 2023Article
- Nutrient regulation of the islet epigenome controls adaptive insulin secretion.The Journal of clinical investigation · 2023Article
- Role of Delta/Notch-like EGF-related receptor in blood glucose homeostasis.Frontiers in endocrinology · 2023Article
- Enhancer of Zeste Homolog 2 (EZH2) Mediates Glucolipotoxicity-Induced Apoptosis in β-Cells.International journal of molecular sciences · 2020Article
- Effect of dietary restriction and subsequent re-alimentation on the transcriptional profile of bovine jejunal epithelium.PloS one · 2018Article
- Role of sulfiredoxin as a peroxiredoxin-2 denitrosylase in human iPSC-derived dopaminergic neurons.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Tumor promoter-induced sulfiredoxin is required for mouse skin tumorigenesis.Carcinogenesis · 2014Article
- Role of sulfiredoxin in systemic diseases influenced by oxidative stress.Redox biology · 2014Review
- Glucose regulation of a cell cycle gene module is selectively lost in mouse pancreatic islets during ageing.Diabetologia · 2013Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPhysiological long term adaptation of pancreatic beta cells is driven by stimuli such as glucose and incretin hormones acting via cAMP (e.g. GLP-1) and involves regulated gene expression. Several rapidly inducible immediate-early genes (IEGs) have been identified in beta cells. Many of these IEGs code for transcription factors and have the potential to control the transcription of downstream target genes likely involved in long term cellular adaptation. The identity of these target genes has not been determined, and the sequence of events occurring during beta cell adaptation is still unclear.
resultsWe have developed a microarray-based strategy for the systematic search of targets. In Min6 insulin-secreting cells, we identified 592 targets and 1278 IEGs responding to a co-stimulation with glucose and cAMP. Both IEGs and targets were involved in a large panel of functions, including those important to beta cell physiology (metabolism, secretion). Nearly 200 IEGs were involved in signaling and transcriptional regulation. To find specific examples of the regulatory link between IEGs and targets, target promoter sequences were analyzed in silico. Statistically significant over-representation of AP-1 response elements notably suggested an important role for this transcription factor, which was experimentally verified. Indeed, cell stimulation altered expression of IEG-encoded components of the AP-1 complex, activating AP-1-dependent transcription. Loss and gain-of-function experiments furthermore allowed to validate a new AP-1 regulated gene (sulfiredoxin) among the targets. AP-1 and sulfiredoxin are sequentially induced also in primary cells from rat islets of Langerhans.
conclusionBy identifying IEGs and their downstream targets, this study brings a comprehensive description of the transcriptional response occurring after beta cell stimulation, as well as new mechanistic insights concerning the AP-1 transcription factor.
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