Redox signal-mediated enhancement of the temperature sensitivity of Transient Receptor Potential Melastatin 2 (TRPM2) elevated glucose-induced insulin secretion from pancreatic islets [Signal Transduction]

March 27th, 2015 by Kashio, M., Tominaga, M.

Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive Ca2+- permeable cation channel expressed by pancreatic β-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 β-cells of wild-type (Wt) mice, but not in TRPM2KO cells. TRPM2-mediated [Ca2+]i increases were likely caused by Ca2+ influx through the plasma membrane because the responses were abolished in the absence of extracellular Ca2+. In addition, TRPM2 activation downstream from the redox signal plus glucose stimulation enhanced glucose-induced insulin secretion. H2O2 application at 37oC induced [Ca2+]i increases not only in Wt but also in TRPM2KO β-cells. This was likely due to the effect of H2O2 on KATP channel activity. However, the N-acetyl cysteine (NAC)-sensitive fraction of insulin secretion by Wt islets was increased by temperature elevation and this temperature-dependent enhancement was significantly diminished in TRPM2KO islets. These data suggest that endogenous redox signals in pancreatic β-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.
  • Posted in Journal of Biological Chemistry, Publications
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