title: TRPM2 modulates insulin secretion in pancreatic β-cells.
abstract: Insulin secretion from pancreatic β-cells is the primary mechanism by which the body lowers blood glucose concentrations. Glucose is the principal stimulator of insulin secretion, and the primary pathway involved in glucose-stimulated insulin secretion is the ATP-sensitive K+ channel voltage-gated Ca2+ channel-mediated pathway. Several TRP channels expressed in pancreatic β-cells have been reported to be involved in insulin secretion. One recent report found that TRPM2 is expressed in pancreatic β-cells and modulates insulin secretion stimulated by glucose and further potentiated by incretin hormones. TRPM2 is a Ca2+-permeable non-selective cation channel activated by adenosine dinucleotides, hydrogen peroxide, and intracellular Ca2+. Glucose tolerance was impaired and insulin secretion was decreased in TRPM2 knockout mice. Insulin secretion via TRPM2 occurs not only through control of intracellular Ca2+ concentrations but also through Ca2+ influx-independent mechanisms. Although further examination is needed to clarify the mechanism of TRPM2-mediated insulin secretion, TRPM2 may be a key player in regulation of insulin secretion and could represent a new target for diabetes therapy.
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institute of Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi, Japan.
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Uchida
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018149:Glucose Intolerance / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D050053:TRPM Cation Channels / Q000235:genetics / Q000502:physiology*
chemical_list: D007328:Insulin; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; C544443:TRPM2 protein, mouse