| First Author | Kumar A | Year | 2018 |
| Journal | Diabetes | Volume | 67 |
| Issue | 8 | Pages | 1561-1575 |
| PubMed ID | 29764859 | Mgi Jnum | J:264034 |
| Mgi Id | MGI:6192431 | Doi | 10.2337/db17-0943 |
| Citation | Kumar A, et al. (2018) Activation of Nrf2 Is Required for Normal and ChREBPalpha-Augmented Glucose-Stimulated beta-Cell Proliferation. Diabetes 67(8):1561-1575 |
| abstractText | Patients with both major forms of diabetes would benefit from therapies that increase beta-cell mass. Glucose, a natural mitogen, drives adaptive expansion of beta-cell mass by promoting beta-cell proliferation. We previously demonstrated that a carbohydrate response element-binding protein (ChREBPalpha) is required for glucose-stimulated beta-cell proliferation and that overexpression of ChREBPalpha amplifies the proliferative effect of glucose. Here we found that ChREBPalpha reprogrammed anabolic metabolism to promote proliferation. ChREBPalpha increased mitochondrial biogenesis, oxygen consumption rates, and ATP production. Proliferation augmentation by ChREBPalpha required the presence of ChREBPbeta. ChREBPalpha increased the expression and activity of Nrf2, initiating antioxidant and mitochondrial biogenic programs. The induction of Nrf2 was required for ChREBPalpha-mediated mitochondrial biogenesis and for glucose-stimulated and ChREBPalpha-augmented beta-cell proliferation. Overexpression of Nrf2 was sufficient to drive human beta-cell proliferation in vitro; this confirms the importance of this pathway. Our results reveal a novel pathway necessary for beta-cell proliferation that may be exploited for therapeutic beta-cell regeneration. |
