ArticleAmerican journal of physiology. Endocrinology and metabolism2011
Cool-1/βPIX functions as a guanine nucleotide exchange factor in the cycling of Cdc42 to regulate insulin secretion.
Article in American journal of physiology. Endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 42 citations in OpenAlex.
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- Serotonin Influences Insulin Secretion in Rat Insulinoma INS-1E Cells.International journal of molecular sciences · 2024Article
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- Novel regulatory roles of small G protein GDP dissociation stimulator (smgGDS) in insulin secretion from pancreatic β-cells.Molecular and cellular endocrinology · 2024Article
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- Cholesterol Redistribution in Pancreatic β-Cells: A Flexible Path to Regulate Insulin Secretion.Biomolecules · 2023Review
- Elevated alanine aminotransferase is associated with biphasic insulin secretion in the healthy elderly Han Chinese population.The Journal of international medical research · 2022Article
- Underappreciated roles for Rho GDP dissociation inhibitors (RhoGDIs) in cell function: Lessons learned from the pancreatic islet β-cell.Biochemical pharmacology · 2022Review
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- Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet.International journal of molecular sciences · 2020Article
- GPCRs, G Proteins, and Their Impact on β-cell Function.Comprehensive Physiology · 2020Review
- Role of Caveolin-1 in Diabetes and Its Complications.Oxidative medicine and cellular longevity · 2020Review
- Quantitative proteomics reveals novel interaction partners of Rac1 in pancreatic β-cells: Evidence for increased interaction with Rac1 under hyperglycemic conditions.Molecular and cellular endocrinology · 2019Article
- Cdc42: A Novel Regulator of Insulin Secretion and Diabetes-Associated Diseases.International journal of molecular sciences · 2019Review
- Transgenerational Obesity and Alteration of ARHGEF11 in the Rat Liver Induced by Intrauterine Hyperglycemia.Journal of diabetes research · 2019Article
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- Mechanisms of the amplifying pathway of insulin secretion in the β cell.Pharmacology & therapeutics · 2017Review
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7 authors at 2 institutions in 1 country.
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Abstract
Second-phase insulin release requires the sustained mobilization of insulin granules from internal storage pools to the cell surface for fusion with the plasma membrane. However, the detailed mechanisms underlying this process remain largely unknown. GTP-loading of the small GTPase Cdc42 is the first glucose-specific activation step in the process, although how glucose triggers Cdc42 activation is entirely unknown. In a directed candidate screen for guanine nucleotide exchange factors (GEFs), which directly activate small GTPases, Cool-1/βPix was identified in pancreatic islet beta cells. In support of its role as the beta cell Cdc42 GEF, βPix coimmunoprecipitated with Cdc42 in human islets and MIN6 beta cells in a glucose-dependent manner, peaking just prior to Cdc42 activation. Furthermore, RNAi-mediated βPix reduction by 50% corresponded to full ablation of glucose-induced Cdc42 activation and significant attenuation of basal and glucose-stimulated insulin secretion. Of the two Cdc42 guanine nucleotide dissociation inhibitor (GDI) proteins identified in beta cells, βPix competed selectively with caveolin-1 (Cav-1) but not RhoGDI in coimmunoprecipitation and GST-Cdc42-GDP interaction assays. However, a phospho-deficient Cav-1-Y14F mutant failed to compete with βPix; Cav-1(Tyr14) is an established phosphorylation site for Src kinase. Taken together, these data support a new model, wherein glucose stimulates Cav-1 and induces its dissociation from Cdc42, possibly via Src kinase activation to phosphorylate Cav-1(Tyr14), to promote Cdc42-βPix binding and Cdc42 activation, and to trigger downstream signaling and ultimately sustain insulin release.
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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.