| First Author | Laurent G | Year | 2008 |
| Journal | Cell Metab | Volume | 7 |
| Issue | 2 | Pages | 113-24 |
| PubMed ID | 18249171 | Mgi Jnum | J:132138 |
| Mgi Id | MGI:3775173 | Doi | 10.1016/j.cmet.2007.12.010 |
| Citation | Laurent G, et al. (2008) Oxidative stress contributes to aging by enhancing pancreatic angiogenesis and insulin signaling. Cell Metab 7(2):113-24 |
| abstractText | JunD, a transcription factor of the AP-1 family, protects cells against oxidative stress. Here, we show that junD(-/-) mice exhibit features of premature aging and shortened life span. They also display persistent hypoglycemia due to enhanced insulin secretion. Consequently, the insulin/IGF-1 signaling pathways are constitutively stimulated, leading to inactivation of FoxO1, a positive regulator of longevity. Hyperinsulinemia most likely results from enhanced pancreatic islet vascularization owing to chronic oxidative stress. Indeed, accumulation of free radicals in beta cells enhances VEGF-A transcription, which in turn increases pancreatic angiogenesis and insulin secretion. Accordingly, long-term treatment with an antioxidant rescues the phenotype of junD(-/-) mice. Indeed, dietary antioxidant supplementation was protective against pancreatic angiogenesis, hyperinsulinemia, and subsequent activation of insulin signaling cascades in peripheral tissues. Taken together, these data establish a pivotal role for oxidative stress in systemic regulation of insulin and define a key role for the JunD protein in longevity. |
