| First Author | Sassmann A | Year | 2010 |
| Journal | J Clin Invest | Volume | 120 |
| Issue | 6 | Pages | 2184-93 |
| PubMed ID | 20440069 | Mgi Jnum | J:161458 |
| Mgi Id | MGI:4459350 | Doi | 10.1172/JCI41541 |
| Citation | Sassmann A, et al. (2010) The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice. J Clin Invest 120(6):2184-93 |
| abstractText | A variety of neurotransmitters, gastrointestinal hormones, and metabolic signals are known to potentiate insulin secretion through GPCRs. We show here that beta cell-specific inactivation of the genes encoding the G protein alpha-subunits Galphaq and Galpha11 resulted in impaired glucose tolerance and insulin secretion in mice. Interestingly, the defects observed in Galphaq/Galpha11-deficient beta cells were not restricted to loss of muscarinic or metabolic potentiation of insulin release; the response to glucose per se was also diminished. Electrophysiological recordings revealed that glucose-induced depolarization of isolated beta cells was impaired in the absence of Galphaq/Galpha11, and closure of KATP channels was inhibited. We provide evidence that this reduced excitability was due to a loss of beta cell-autonomous potentiation of insulin secretion through factors cosecreted with insulin. We identified as autocrine mediators involved in this process extracellular nucleotides such as uridine diphosphate acting through the Gq/G11-coupled P2Y6 receptor and extracellular calcium acting through the calcium-sensing receptor. Thus, the Gq/G11-mediated signaling pathway potentiates insulin secretion in response to glucose by integrating systemic as well as autocrine/paracrine mediators. |
