Abstract
There are six thermosensitive TRP channels in mammals, and there might be other TRP channels sensitive to temperature stimuli. Recently, we have demonstrated that TRPM2 can be activated by exposure to warm temperatures (>35°C) apparently via direct heat-evoked channel gating. β-NAD+- or ADP-ribose-evoked TRPM2 activity is robustly potentiated at elevated temperatures. We have also reported that, even though cyclic ADP-ribose (cADP-ribose) does not activate TRPM2 at 25°C, co-application of heat and intracellular cADP-ribose dramatically potentiates TRPM2 activity. Here we show that in rodent pancreatic islets, TRPM2 is co-expressed with insulin, and mild heating (around body temperature) of these cells evokes increases in both cytosolic Ca2+ and insulin release which is KATP channel-independent and cAMP-mediated. Heat-evoked response in pancreatic islets was significantly diminished by applying the known TRPM2 inhibitors; nonsteroidal anti-inflammatory drug flufenamic acid (FFA), anti-fungal reagent econazole or 2-aminoethoxydiphenyl borate (2-APB), and by treatment with TRPM2-specific siRNA. These results suggest that TRPM2 regulates Ca2+ entry into pancreatic β-cells at body temperature depending on production of cADPR-related molecules, thereby regulating insulin secretion. [J Physiol Sci. 2006;56 Suppl:S159]
