| First Author | Uchida K | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 1 | Pages | 119-26 |
| PubMed ID | 20921208 | Mgi Jnum | J:169329 |
| Mgi Id | MGI:4940445 | Doi | 10.2337/db10-0276 |
| Citation | Uchida K, et al. (2011) Lack of TRPM2 impaired insulin secretion and glucose metabolisms in mice. Diabetes 60(1):119-26 |
| abstractText | OBJECTIVE: TRPM2 is a Ca(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(2)(+) increase in immunocytes and pancreatic beta-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(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 beta-cells, smaller intracellular Ca(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. |
