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- Title
Lack of TRPM2 Impaired Insulin Secretion and Glucose Metabolisms in Mice.
- Authors
Uchida, Kunitoshi; Dezaki, Katsuya; Damdindorj, Boldbaatar; Inada, Hitoshi; Shiuchi, Tetsuya; Mori, Yasuo; Yada, Toshihiko; Minokoshi, Yasuhiko; Tominaga, Makoto
- Abstract
OBJECTIVE--TRPM2 is a Ca[sup 2+]-permeable nonselective cation channel activated by adenosine dinucleotides. We previously demonstrated that TRPM2 is activated by coapplication of heat and intracellular cyclic adenosine 5'-diphosphoribose, which has been suggested to be involved in intracellular Ca[sup 2+] increase in immunocytes and pancreatic β-cells. To clarify the involvement of TRPM2 in insulin secretion, we analyzed TRPM2 knockout (TRPM2-KO) mice. RESEARCH DESIGN AND METHODS--Oral and intraperitoneal glucose tolerance tests (OGTT and IPGTT) were performed in TRPM2-KO and wild-type mice. We also measured cytosolic free Ca[sup 2+] in single pancreatic cells using fura-2 microfluorometry and insulin secretion from pancreatic islets. RESULTS--Basal blood glucose levels were higher in TRPM2-KO mice than in wild-type mice without any difference in plasma insulin levels. The OGTT and IPGTT demonstrated that blood glucose levels in TRPM2-KO mice were higher than those in wild-type mice, which was associated with an impairment in insulin secretion. In isolated β-cells, smaller intracellular Ca[sup 2+] increase was observed in response to high concentrations of glucose and incretin hormone in TRPM2-KO cells than in wild-type cells. Moreover, insulin secretion from the islets of TRPM2-KO mice in response to glucose and incretin hormone treatment was impaired, whereas the response to tolbutamide, an ATP-sensitive potassium channel inhibitor, was not different between the two groups. CONCLUSIONS--These results indicate that TRPM2 is involved in insulin secretion stimulated by glucose and that further potentiated by incretins. Thus, TRPM2 may be a new target for diabetes therapy. Diabetes 60:119-126, 2011
- Subjects
INSULIN research; ADENOSINES; CATIONS; PANCREATIC beta cells; GLUCOSE tolerance tests; POTASSIUM channels
- Publication
Diabetes, 2011, Vol 60, Issue 1, p119
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db10-0276