| First Author | Basco D | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 546 |
| PubMed ID | 29416045 | Mgi Jnum | J:257792 |
| Mgi Id | MGI:6119146 | Doi | 10.1038/s41467-018-03034-0 |
| Citation | Basco D, et al. (2018) alpha-cell glucokinase suppresses glucose-regulated glucagon secretion. Nat Commun 9(1):546 |
| abstractText | Glucagon secretion by pancreatic alpha-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that alpha-cell glucokinase (Gck) plays a role in the control of glucagon secretion. Using mice with alpha-cell-specific inactivation of Gck (alphaGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of KATP channels in alpha-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels. alphaGckKO mice display hyperglucagonemia in the fed state, which is associated with increased hepatic gluconeogenic gene expression and hepatic glucose output capacity. In adult mice, fed hyperglucagonemia is further increased and glucose intolerance develops. Thus, glucokinase governs an alpha-cell metabolic pathway that suppresses secretion at or above normoglycemic levels; abnormal suppression of glucagon secretion deregulates hepatic glucose metabolism and, over time, induces a pre-diabetic phenotype. |
