| First Author | Johnson JD | Year | 2004 |
| Journal | J Biol Chem | Volume | 279 |
| Issue | 23 | Pages | 24794-802 |
| PubMed ID | 15044459 | Mgi Jnum | J:123988 |
| Mgi Id | MGI:3720302 | Doi | 10.1074/jbc.M401216200 |
| Citation | Johnson JD, et al. (2004) RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets. J Biol Chem 279(23):24794-802 |
| abstractText | Cells are programmed to die when critical signaling and metabolic pathways are disrupted. Inhibiting the type 2 ryanodine receptor (RyR2) in human and mouse pancreatic beta-cells markedly increased apoptosis. This mode of programmed cell death was not associated with robust caspase-3 activation prompting a search for an alternative mechanism. Increased calpain activity and calpain gene expression suggested a role for a calpain-dependent death pathway. Using a combination of pharmacological and genetic approaches, we demonstrated that the calpain-10 isoform mediated ryanodine-induced apoptosis. Apoptosis induced by the fatty acid palmitate and by low glucose also required calpain-10. Ryanodine-induced calpain activation and apoptosis were reversed by glucagon-like peptide or short-term exposure to high glucose. Thus RyR2 activity seems to play an essential role in beta-cell survival in vitro by suppressing a death pathway mediated by calpain-10, a type 2 diabetes susceptibility gene with previously unknown function. |
