| First Author | Kashio M | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 19 | Pages | 12435-42 |
| PubMed ID | 25817999 | Mgi Jnum | J:222577 |
| Mgi Id | MGI:5644892 | Doi | 10.1074/jbc.M115.649913 |
| Citation | Kashio M, et al. (2015) Redox Signal-mediated Enhancement of the Temperature Sensitivity of Transient Receptor Potential Melastatin 2 (TRPM2) Elevates Glucose-induced Insulin Secretion from Pancreatic Islets. J Biol Chem 290(19):12435-42 |
| abstractText | Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive Ca(2+)-permeable cation channel expressed by pancreatic beta cells where channel function is constantly affected by body temperature. We focused on the physiological functions of redox signal-mediated TRPM2 activity at body temperature. H2O2, an important molecule in redox signaling, reduced the temperature threshold for TRPM2 activation in pancreatic beta cells of WT mice but not in TRPM2KO cells. TRPM2-mediated [Ca(2+)]i increases were likely caused by Ca(2+) influx through the plasma membrane because the responses were abolished in the absence of extracellular Ca(2+). In addition, TRPM2 activation downstream from the redox signal plus glucose stimulation enhanced glucose-induced insulin secretion. H2O2 application at 37 degrees C induced [Ca(2+)]i increases not only in WT but also in TRPM2KO beta cells. This was likely due to the effect of H2O2 on KATP channel activity. However, the N-acetylcysteine-sensitive fraction of insulin secretion by WT islets was increased by temperature elevation, and this temperature-dependent enhancement was diminished significantly in TRPM2KO islets. These data suggest that endogenous redox signals in pancreatic beta cells elevate insulin secretion via TRPM2 sensitization and activity at body temperature. The results in this study could provide new therapeutic approaches for the regulation of diabetic conditions by focusing on the physiological function of TRPM2 and redox signals. |
