ArticleProceedings of the National Academy of Sciences of the United States of America2007
Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 215 papers.
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Who cites it
215 citing papers in PubMed, 418 citations in OpenAlex.
- G protein-coupled receptor 119 agonist DS-8500a effects on pancreatic β-cells in Japanese type 2 diabetes mellitus patients.Journal of diabetes investigation · 2019Trial
- Teneligliptin, a Dipeptidyl Peptidase-4 Inhibitor, Improves Early-Phase Insulin Secretion in Drug-Naïve Patients with Type 2 Diabetes.Drugs in R&D · 2015Trial
- Article
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Altered GScience advances · 2026Article
- IG20/MADD gene functional isoform KIAA0358 can promote insulin secretion in glucose and repaglinide-induced pancreatic β-cells.Acta pharmacologica Sinica · 2026Article
- Gene expression profiles associated with stimulus-responsive insulin secretion in insulinoma.Endocrine connections · 2026Article
- Breast Cancer-Secreted DPP3 Promotes Lung Metastasis by Remodelling the Vascular Niche in Lung via the Rap1 Signalling Pathway.Journal of extracellular vesicles · 2025Article
- Submembrane liprin-α1 clusters spatially localize insulin granule fusion.The Journal of cell biology · 2025Article
- ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver.Communications biology · 2025Article
- Physiology and clinical applications of GIP.Endocrine journal · 2025Review
- Epac1 mediates thermogenesis and lipolysis in white adipose tissue via the p38γ-NFAT5 axis in a PKA-independent manner.Clinical science (London, England : 1979) · 2025Article
- Characteristics of Berberine Effects on Insulin Exocytosis in Pancreatic β Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Engineering Baker's Yeast for Efficient cAMP Synthesis via Regulation of PKA Activity.Foods (Basel, Switzerland) · 2025Article
- Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments.Pharmacological reviews · 2025Review
- Biphasic glucose-stimulated insulin secretion over decades: a journey from measurements and modeling to mechanistic insights.Life metabolism · 2025Review
- The impact of sulfonylureas on diverse ion channels: an alternative explanation for the antidiabetic actions.Frontiers in cell and developmental biology · 2025Review
- Spatiotemporal orchestration of calcium-cAMP oscillations on AKAP/AC nanodomains is governed by an incoherent feedforward loop.PLoS computational biology · 2024Article
- Article
- Proteomic Analysis of Rap1A GTPase Signaling-Deficient C57BL/6 Mouse Pancreas and Functional Studies Identify an Essential Role of Rap1A in Pancreas Physiology.International journal of molecular sciences · 2024Article
155 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
cAMP is well known to regulate exocytosis in various secretory cells, but the precise mechanism of its action remains unknown. Here, we examine the role of cAMP signaling in the exocytotic process of insulin granules in pancreatic beta cells. Although activation of cAMP signaling alone does not cause fusion of the granules to the plasma membrane, it clearly potentiates both the first phase (a prompt, marked, and transient increase) and the second phase (a moderate and sustained increase) of glucose-induced fusion events. Interestingly, all granules responsible for this potentiation are newly recruited and immediately fused to the plasma membrane without docking (restless newcomer). Importantly, cAMP-potentiated fusion events in the first phase of glucose-induced exocytosis are markedly reduced in mice lacking the cAMP-binding protein Epac2 (Epac2(ko/ko)). In addition, the small GTPase Rap1, which is activated by cAMP specifically through Epac2 in pancreatic beta cells, mediates cAMP-induced insulin secretion in a protein kinase A-independent manner. We also have developed a simulation model of insulin granule movement in which potentiation of the first phase is associated with an increase in the insulin granule density near the plasma membrane. Taken together, these data indicate that Epac2/Rap1 signaling is essential in regulation of insulin granule dynamics by cAMP, most likely by controlling granule density near the plasma membrane.
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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.