Gαo Represses Insulin Secretion by Reducing Vesicular Docking in Pancreatic β-Cells
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Molecular physiology of G-protein regulation of insulin secretion.
The study examines insulin secretion and pancreatic biology, not research practice.
Cell biology of G-protein regulation of insulin secretion, domain biomedical science.
Abstract
OBJECTIVE: Pertussis toxin uncoupling-based studies have shown that Gαi and Gαo can inhibit insulin secretion in pancreatic β-cells. Yet it is unclear whether Gαi and Gαo operate through identical mechanisms and how these G-protein-mediated signals inhibit insulin secretion in vivo. Our objective is to examine whether/how Gαo regulates islet development and insulin secretion in β-cells. RESEARCH DESIGN AND METHODS: Immunoassays were used to analyze the Gαo expression in mouse pancreatic cells. Gαo was specifically inactivated in pancreatic progenitor cells by pancreatic cell-specific gene deletion. Hormone expression and insulin secretion in response to different stimuli were assayed in vivo and in vitro. Electron microscope and total internal reflection fluorescence-based assays were used to evaluate how Gαo regulates insulin vesicle docking and secretion in response to glucose stimulation. RESULTS: Islet cells differentiate properly in Gαo(-/-) mutant mice. Gαo inactivation significantly enhances insulin secretion both in vivo and in isolation. Gαo nullizygous β-cells contain an increased number of insulin granules docked on the cell plasma membrane, although the total number of vesicles per β-cell remains unchanged. CONCLUSIONS: Gαo is not required for endocrine islet cell differentiation, but it regulates the number of insulin vesicles docked on the β-cell membrane.
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The record
- Venue
- Diabetes
- Topic
- Pancreatic function and diabetes
- Field
- Medicine
- Canadian institutions
- Université de Sherbrooke
- Funders
- National Institute of Diabetes and Digestive and Kidney DiseasesJapan Society for the Promotion of ScienceNational Institutes of HealthAstellas Foundation for Research on Metabolic DisordersVanderbilt Diabetes Research and Training Center, Vanderbilt University Medical CenterAstellas PharmaVanderbilt UniversityResearch Foundation for Opto-Science and TechnologyNational Institute of Environmental Health SciencesU.S. Department of Veterans Affairs
- Keywords
- InsulinSecretionBiologyIsletEndocrinologyInternal medicineIn vivoEnteroendocrine cellCell biologyHormoneEndocrine systemMedicine
- Has abstract in OpenAlex
- yes