| First Author | Zhang T | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 3 | Pages | 1055-70 |
| PubMed ID | 26727107 | Mgi Jnum | J:323787 |
| Mgi Id | MGI:6835300 | Doi | 10.1210/en.2015-1852 |
| Citation | Zhang T, et al. (2016) FoxO1 Plays an Important Role in Regulating beta-Cell Compensation for Insulin Resistance in Male Mice. Endocrinology 157(3):1055-70 |
| abstractText | beta-Cell compensation is an essential mechanism by which beta-cells increase insulin secretion for overcoming insulin resistance to maintain euglycemia in obesity. Failure of beta-cells to compensate for insulin resistance contributes to insulin insufficiency and overt diabetes. To understand the mechanism of beta-cell compensation, we characterized the role of forkhead box O1 (FoxO1) in beta-cell compensation in mice under physiological and pathological conditions. FoxO1 is a key transcription factor that serves as a nutrient sensor for integrating insulin signaling to cell metabolism, growth, and proliferation. We showed that FoxO1 improved beta-cell compensation via 3 distinct mechanisms by increasing beta-cell mass, enhancing beta-cell glucose sensing, and augmenting beta-cell antioxidative function. These effects accounted for increased glucose-stimulated insulin secretion and enhanced glucose tolerance in beta-cell-specific FoxO1-transgenic mice. When fed a high-fat diet, beta-cell-specific FoxO1-transgenic mice were protected from developing fat-induced glucose disorder. This effect was attributable to increased beta-cell mass and function. Furthermore, we showed that FoxO1 activity was up-regulated in islets, correlating with the induction of physiological beta-cell compensation in high-fat-induced obese C57BL/6J mice. These data characterize FoxO1 as a pivotal factor for orchestrating physiological adaptation of beta-cell mass and function to overnutrition and obesity. |
