| First Author | Sumara G | Year | 2009 |
| Journal | Cell | Volume | 136 |
| Issue | 2 | Pages | 235-48 |
| PubMed ID | 19135240 | Mgi Jnum | J:146185 |
| Mgi Id | MGI:3836870 | Doi | 10.1016/j.cell.2008.11.018 |
| Citation | Sumara G, et al. (2009) Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis. Cell 136(2):235-48 |
| abstractText | Dysfunction and loss of insulin-producing pancreatic beta cells represent hallmarks of diabetes mellitus. Here, we show that mice lacking the mitogen-activated protein kinase (MAPK) p38delta display improved glucose tolerance due to enhanced insulin secretion from pancreatic beta cells. Deletion of p38delta results in pronounced activation of protein kinase D (PKD), the latter of which we have identified as a pivotal regulator of stimulated insulin exocytosis. p38delta catalyzes an inhibitory phosphorylation of PKD1, thereby attenuating stimulated insulin secretion. In addition, p38delta null mice are protected against high-fat-feeding-induced insulin resistance and oxidative stress-mediated beta cell failure. Inhibition of PKD1 reverses enhanced insulin secretion from p38delta-deficient islets and glucose tolerance in p38delta null mice as well as their susceptibility to oxidative stress. In conclusion, the p38delta-PKD pathway integrates regulation of the insulin secretory capacity and survival of pancreatic beta cells, pointing to a pivotal role for this pathway in the development of overt diabetes mellitus. |
