Physiological significance of thermosensitive TRPM2 channel

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Transient receptor potential melastatin 2 (TRPM2) is a non-selective Ca^<2+>-permeable cation channel, and is known to be activated by adenosine 5'-diphosphoribose (ADP-ribose) and hydrogen peroxide. 1) Upon screening of the compounds, it was clarified that 2-aminoethoxydiphenyl borate (2-APB) exhibited the rapid and reversible inhibition of TRPM2 channels and that 2-APB inhibited heat-evoked insulin release from the pancreatic islets. 2) To clarify the involvement of TRPM2 in insulin secretion, we analyzed TRPM2 knock-out (TRPM2-KO) mice, and found that TRPM2 is involved in insulin secretion stimulated by glucose and that further potentiated by incretins, suggesting that TRPM2 may be a new target for diabetes therapy. 3) To determine the effects of a small reduction in ambient temperature on energy metabolism, we compared two groups of mice ; one exposed to a cool environment (20℃) and the other maintained in a near-thermoneutral environment (25℃) for 10 days. We found that a small reduction in ambient temperature can affect glucose homeostasis through regulation of insulin secretion and preferentially enhances fat storage in IWAT.