Lack of TRPM2 impaired insulin secretion and glucose metabolisms in mice

Kunitoshi Uchida, Katsuya Dezaki, Boldbaatar Damdindorj, Hitoshi Inada, Tetsuya Shiuchi, Yasuo Mori, Toshihiko Yada, Yasuhiko Minokoshi, Makoto Tominaga

研究成果: Article査読

136 被引用数 (Scopus)

抄録

OBJECTIVE-TRPM2 is a Ca2+-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 Ca2+ 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 Ca2+ 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 Ca2+ increase was observed in response to high concentrations of glucose and incretin hormone in TRPM2-KO cells than in wildtype 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.

本文言語English
ページ(範囲)119-126
ページ数8
ジャーナルDiabetes
60
1
DOI
出版ステータスPublished - 2011 1月
外部発表はい

ASJC Scopus subject areas

  • 内科学
  • 内分泌学、糖尿病および代謝内科学

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