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

Aizhen Zhao, Mica Ohara-Imaizumi, Marcella Brissova, Richard K.P. Benninger, Yanwen Xu, Yuhan Hao, Joel Abramowitz, Guylain Boulay, Alvin C. Powers, David Piston, Meisheng Jiang, Shinya Nagamatsu, Lutz Birnbaumer, Oqiang Gu

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish
Pages (from-to)2522-2529
Number of pages8
Issue number10
StatePublished - Oct 2010


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