| First Author | Briant LJB | Year | 2018 |
| Journal | Cell Rep | Volume | 23 |
| Issue | 11 | Pages | 3300-3311 |
| PubMed ID | 29898400 | Mgi Jnum | J:270771 |
| Mgi Id | MGI:6278704 | Doi | 10.1016/j.celrep.2018.05.035 |
| Citation | Briant LJB, et al. (2018) CPT1a-Dependent Long-Chain Fatty Acid Oxidation Contributes to Maintaining Glucagon Secretion from Pancreatic Islets. Cell Rep 23(11):3300-3311 |
| abstractText | Glucagon, the principal hyperglycemic hormone, is secreted from pancreatic islet alpha cells as part of the counter-regulatory response to hypoglycemia. Hence, secretory output from alpha cells is under high demand in conditions of low glucose supply. Many tissues oxidize fat as an alternate energy substrate. Here, we show that glucagon secretion in low glucose conditions is maintained by fatty acid metabolism in both mouse and human islets, and that inhibiting this metabolic pathway profoundly decreases glucagon output by depolarizing alpha cell membrane potential and decreasing action potential amplitude. We demonstrate, by using experimental and computational approaches, that this is not mediated by the KATP channel, but instead due to reduced operation of the Na(+)-K(+) pump. These data suggest that counter-regulatory secretion of glucagon is driven by fatty acid metabolism, and that the Na(+)-K(+) pump is an important ATP-dependent regulator of alpha cell function. |
