| First Author | Fransson L | Year | 2014 |
| Journal | Mol Cell Endocrinol | Volume | 383 |
| Issue | 1-2 | Pages | 126-36 |
| PubMed ID | 24361515 | Mgi Jnum | J:211851 |
| Mgi Id | MGI:5576808 | Doi | 10.1016/j.mce.2013.12.010 |
| Citation | Fransson L, et al. (2014) Mitogen-activated protein kinases and protein phosphatase 5 mediate glucocorticoid-induced cytotoxicity in pancreatic islets and beta-cells. Mol Cell Endocrinol 383(1-2):126-36 |
| abstractText | Glucocorticoid excess is associated with glucose intolerance and diabetes. In addition to inducing insulin resistance, glucocorticoids impair beta-cell function and cause beta-cell apoptosis. In this study we show that dexamethasone activates mitogen-activated protein kinases (MAPKs) signaling in MIN6 beta-cells, as evident by enhanced phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK). In contrast, the integrated stress response pathway was inhibited by dexamethasone. A p38 MAPK inhibitor attenuated dexamethasone-induced apoptosis in beta-cells and isolated islets and decreased glucocorticoid receptor phosphorylation at S220. In contrast, a JNK inhibitor augmented DNA fragmentation and dexamethasone-induced formation of cleaved caspase 3. We also show that inhibition of protein phosphatase 5 (PP5) augments apoptosis in dexamethasone-exposed islets and beta-cells, with a concomitant activation of p38 MAPK. In conclusion, our data provide evidence that in islets and beta-cells, p38 MAPK and JNK phosphorylation work in concert with PP5 to regulate the cytotoxic effects exerted by glucocorticoids. |
