ArticleCell reports2015
Feedback inhibition of CREB signaling promotes beta cell dysfunction in insulin resistance.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 76 citations in OpenAlex.
- Stimulation to secrete insulin induces pancreatic β-cell dysfunction through Tfe3 activation.iScience · 2026Article
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- Immunoglobulin A controls intestinal virus colonization to preserve immune homeostasis.Cell host & microbe · 2025Article
- Spint1 disruption in mouse pancreas leads to glucose intolerance and impaired insulin production involving HEPSIN/MAFA.Nature communications · 2024Article
- Refined tamoxifen administration in mice by encouraging voluntary consumption of palatable formulations.Lab animal · 2024Article
- PKIB, a Novel Target for Cancer Therapy.International journal of molecular sciences · 2024Review
- Adipose Tissue Hypoxia in Obesity: Clinical Reappraisal of Hypoxia Hypothesis.Advances in experimental medicine and biology · 2024Review
- CaFrontiers in endocrinology · 2024Review
- Impaired BCAA catabolism in adipose tissues promotes age-associated metabolic derangement.Nature aging · 2023Article
- Noncanonical Regulation of cAMP-Dependent Insulin Secretion and Its Implications in Type 2 Diabetes.Comprehensive Physiology · 2023Article
- Review
- Nutrient regulation of the islet epigenome controls adaptive insulin secretion.The Journal of clinical investigation · 2023Article
- Edmond Fischer's kinase legacy: History of the protein kinase inhibitor and protein kinase A.IUBMB life · 2023Article
- Expression Silencing of Mitogen-Activated Protein Kinase 8 Interacting Protein-1 Conferred Its Role in Pancreatic β-Cell Physiology and Insulin Secretion.Metabolites · 2023Article
- The CRHR1/CREB/REST signaling cascade regulates mammalian embryonic neural stem cell properties.EMBO reports · 2023Article
- Microarray analysis of hub genes, non-coding RNAs and pathways in lung after whole body irradiation in a mouse model.International journal of radiation biology · 2023Article
- Review
- Aging compromises human islet beta cell function and identity by decreasing transcription factor activity and inducing ER stress.Science advances · 2022Article
- Role of the Transcription Factor MAFA in the Maintenance of Pancreatic β-Cells.International journal of molecular sciences · 2022Review
- MafA Regulation in β-Cells: From Transcriptional to Post-Translational Mechanisms.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Although persistent elevations in circulating glucose concentrations promote compensatory increases in pancreatic islet mass, unremitting insulin resistance causes deterioration in beta cell function that leads to the progression to diabetes. Here, we show that mice with a knockout of the CREB coactivator CRTC2 in beta cells have impaired oral glucose tolerance due to decreases in circulating insulin concentrations. CRTC2 was found to promote beta cell function in part by stimulating the expression of the transcription factor MafA. Chronic hyperglycemia disrupted cAMP signaling in pancreatic islets by activating the hypoxia inducible factor (HIF1)-dependent induction of the protein kinase A inhibitor beta (PKIB), a potent inhibitor of PKA catalytic activity. Indeed, disruption of the PKIB gene improved islet function in the setting of obesity. These results demonstrate how crosstalk between nutrient and hormonal pathways contributes to loss of pancreatic islet function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.