| First Author | Golson ML | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 11 | Pages | 3829-38 |
| PubMed ID | 26251404 | Mgi Jnum | J:246072 |
| Mgi Id | MGI:5923332 | Doi | 10.2337/db15-0465 |
| Citation | Golson ML, et al. (2015) Activation of FoxM1 Revitalizes the Replicative Potential of Aged beta-Cells in Male Mice and Enhances Insulin Secretion. Diabetes 64(11):3829-38 |
| abstractText | Type 2 diabetes incidence increases with age, while beta-cell replication declines. The transcription factor FoxM1 is required for beta-cell replication in various situations, and its expression declines with age. We hypothesized that increased FoxM1 activity in aged beta-cells would rejuvenate proliferation. Induction of an activated form of FoxM1 was sufficient to increase beta-cell mass and proliferation in 12-month-old male mice after just 2 weeks. Unexpectedly, at 2 months of age, induction of activated FoxM1 in male mice improved glucose homeostasis with unchanged beta-cell mass. Cells expressing activated FoxM1 demonstrated enhanced glucose-stimulated Ca2+ influx, which resulted in improved glucose tolerance through enhanced beta-cell function. Conversely, our laboratory has previously demonstrated that mice lacking FoxM1 in the pancreas display glucose intolerance or diabetes with only a 60% reduction in beta-cell mass, suggesting that the loss of FoxM1 is detrimental to beta-cell function. Ex vivo insulin secretion was therefore examined in size-matched islets from young mice lacking FoxM1 in beta-cells. Foxm1-deficient islets indeed displayed reduced insulin secretion. Our studies reveal that activated FoxM1 increases beta-cell replication while simultaneously enhancing insulin secretion and improving glucose homeostasis, making FoxM1 an attractive therapeutic target for diabetes. |
