title: The role of TRPM2 in pancreatic β-cells and the development of diabetes.
abstract: TRPM2 is a Ca(2+)-permeable non-selective cation channel that can be activated by adenosine dinucleotides, hydrogen peroxide, or intracellular Ca(2+). The protein is expressed in a wide variety of cells, including neurons in the brain, immune cells, endocrine cells, and endothelial cells. This channel is also well expressed in β-cells in the pancreas. Insulin secretion from pancreatic β-cells is the primary mechanism by which the concentration of blood glucose is reduced. Thus, impairment of insulin secretion leads to hyperglycemia and eventually causes diabetes. Glucose is the principal stimulator of insulin secretion. The primary pathway involved in glucose-stimulated insulin secretion is the ATP-sensitive K(+) (KATP) channel to voltage-gated Ca(2+) channel (VGCC)-mediated pathway. Increases in the intracellular Ca(2+) concentration are necessary for insulin secretion, but VGCC is not sufficient to explain [Ca(2+)]i increases in pancreatic β-cells and the resultant secretion of insulin. In this review, we focus on TRPM2 as a candidate for a [Ca(2+)]i modulator in pancreatic β-cells and its involvement in insulin secretion and development of diabetes. Although further analyses are needed to clarify the mechanism underlying TRPM2-mediated insulin secretion, TRPM2 could be a key player in the 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 for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan; Department of Physiological Sciences, The University of Advanced Studies, Okazaki, Aichi 444-8585, Japan. Electronic address: kuchida@nips.ac.jp.
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan; Department of Physiological Sciences, The University of Advanced Studies, Okazaki, Aichi 444-8585, Japan. Electronic address: tominaga@nips.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D002118:Calcium / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005947:Glucose; D006801:Humans; D054795:Incretins / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D050053:TRPM Cation Channels / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: D054795:Incretins; D007328:Insulin; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D005947:Glucose; D002118:Calcium
keywords: Glucose tolerance; Incretin hormone; Inflammation; Insulin resistance; Insulin secretion; Intracellular Ca(2+); Pancreatic β-cell; TRPM2