| First Author | Wang L | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 1 | Pages | 147-57 |
| PubMed ID | 25092678 | Mgi Jnum | J:230240 |
| Mgi Id | MGI:5755790 | Doi | 10.2337/db13-1715 |
| Citation | Wang L, et al. (2015) PTEN deletion in pancreatic alpha-cells protects against high-fat diet-induced hyperglucagonemia and insulin resistance. Diabetes 64(1):147-57 |
| abstractText | An aberrant increase in circulating catabolic hormone glucagon contributes to type 2 diabetes pathogenesis. However, mechanisms regulating glucagon secretion and alpha-cell mass are not well understood. In this study, we aimed to demonstrate that phosphatidylinositol 3-kinase (PI3K) signaling is an important regulator of alpha-cell function. Mice with deletion of PTEN, a negative regulator of this pathway, in alpha-cells show reduced circulating glucagon levels and attenuated l-arginine-stimulated glucagon secretion both in vivo and in vitro. This hypoglucagonemic state is maintained after high-fat-diet feeding, leading to reduced expression of hepatic glycogenolytic and gluconeogenic genes. These beneficial effects protected high-fat diet-fed mice against hyperglycemia and insulin resistance. The data demonstrate an inhibitory role of PI3K signaling on alpha-cell function and provide experimental evidence for enhancing alpha-cell PI3K signaling for diabetes treatment. |
