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- Title
Gαo represses insulin secretion by reducing vesicular docking in pancreatic beta-cells.
- Authors
Zhao A; Ohara-Imaizumi M; Brissova M; Benninger RK; Xu Y; Hao Y; Abramowitz J; Boulay G; Powers AC; Piston D; Jiang M; Nagamatsu S; Birnbaumer L; Gu G; Zhao, Aizhen; Ohara-Imaizumi, Mica; Brissova, Marcella; Benninger, Richard K P; Xu, Yanwen; Hao, Yuhan
- Abstract
<bold>Objective: </bold>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.<bold>Research Design and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Gαo is not required for endocrine islet cell differentiation, but it regulates the number of insulin vesicles docked on the β-cell membrane.
- Publication
Diabetes, 2010, Vol 59, Issue 10, p2522
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db09-1719