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

Diabetes
Aizhen ZhaoGuoqiang Gu

Abstract

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. 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. 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. Gαo is not required for endocrine islet cell differentiat...Continue Reading

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Citations

Jan 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ying WangMeisheng Jiang
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Guanghua TangMeisheng Jiang
Apr 12, 2012·American Journal of Physiology. Cell Physiology·Susanne G Straub, Geoffrey W G Sharp
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Sep 11, 2014·American Journal of Physiology. Endocrinology and Metabolism·Veronika LeissBernd Nürnberg
Jan 24, 2018·Molecular and Cellular Endocrinology·Amy C KellySean W Limesand
May 22, 2021·Frontiers in Cell and Developmental Biology·Tiziana SanaviaGuoqiang Gu

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Methods Mentioned

BETA
confocal microscopy
transmission electron microscopy
fluorescence microscopy

Software Mentioned

Metamorph
Bioquant
TIRFM

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