| First Author | Zhao A | Year | 2010 |
| Journal | Diabetes | Volume | 59 |
| Issue | 10 | Pages | 2522-9 |
| PubMed ID | 20622165 | Mgi Jnum | J:169627 |
| Mgi Id | MGI:4941424 | Doi | 10.2337/db09-1719 |
| Citation | Zhao A, et al. (2010) Galphao represses insulin secretion by reducing vesicular docking in pancreatic beta-cells. Diabetes 59(10):2522-9 |
| abstractText | OBJECTIVE: Pertussis toxin uncoupling-based studies have shown that Galphai and Galphao can inhibit insulin secretion in pancreatic beta-cells. Yet it is unclear whether Galphai and Galphao operate through identical mechanisms and how these G-protein-mediated signals inhibit insulin secretion in vivo. Our objective is to examine whether/how Galphao regulates islet development and insulin secretion in beta-cells. RESEARCH DESIGN AND METHODS: Immunoassays were used to analyze the Galphao expression in mouse pancreatic cells. Galphao 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 Galphao regulates insulin vesicle docking and secretion in response to glucose stimulation. RESULTS: Islet cells differentiate properly in Galphao(-/-) mutant mice. Galphao inactivation significantly enhances insulin secretion both in vivo and in isolation. Galphao nullizygous beta-cells contain an increased number of insulin granules docked on the cell plasma membrane, although the total number of vesicles per beta-cell remains unchanged. CONCLUSIONS: Galphao is not required for endocrine islet cell differentiation, but it regulates the number of insulin vesicles docked on the beta-cell membrane. |
