Gαo represses insulin secretion by reducing vesicular docking in pancreatic beta-cells.

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
Diabetes. 2010 59 (10): 2522-9

PMID: 20622165 · PMCID: PMC3279551 · DOI:10.2337/db09-1719

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.

MeSH Terms (14)

Animals Cell Differentiation Gene Expression Regulation GTP-Binding Protein alpha Subunits Homeodomain Proteins Homeostasis Insulin Insulin-Secreting Cells Insulin Secretion Mice Mice, Knockout Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Trans-Activators

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