G?o represses insulin secretion by reducing vesicular docking in pancreatic beta-cells.

ABSTRACT:

Objective

Pertussis toxin uncoupling-based studies have shown that G?i and G?o can inhibit insulin secretion in pancreatic ?-cells. Yet it is unclear whether G?i and G?o operate through identical mechanisms and how these G-protein-mediated signals inhibit insulin secretion in vivo. Our objective is to examine whether/how G?o regulates islet development and insulin secretion in ?-cells.

Research design and methods

Immunoassays were used to analyze the G?o expression in mouse pancreatic cells. G?o 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 G?o regulates insulin vesicle docking and secretion in response to glucose stimulation.

Results

Islet cells differentiate properly in G?o(-/-) mutant mice. G?o inactivation significantly enhances insulin secretion both in vivo and in isolation. G?o nullizygous ?-cells contain an increased number of insulin granules docked on the cell plasma membrane, although the total number of vesicles per ?-cell remains unchanged.

Conclusions

G?o is not required for endocrine islet cell differentiation, but it regulates the number of insulin vesicles docked on the ?-cell membrane.

SUBMITTER: Zhao A 

PROVIDER: S-EPMC3279551 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature