2010 Fiscal Year Final Research Report
Physiological significance of thermosensitive TRPM2 channel
| Project/Area Number |
19209006
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | National Institutes of Natural Sciences Okazaki Research Facilities |
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Principal Investigator |
TOMINAGA Makoto National Institutes of Natural Sciences Okazaki Research Facilities, 岡崎統合バイオサイエンスセンター, 教授 (90260041)
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| Co-Investigator(Kenkyū-buntansha) |
INADA Hitoshi 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 特任助教 (60419893)
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| Project Period (FY) |
2007 – 2010
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| Keywords | TRPM2チャネル / 免疫機能 / インスリン分泌 / 膵臓 |
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| Research Abstract |
Transient receptor potential melastatin 2 (TRPM2) is a non-selective Ca^<2+>-permeable cation channel, and is known to be activated by adenosine 5'-diphosphoribose (ADP-ribose) and hydrogen peroxide. 1) Upon screening of the compounds, it was clarified that 2-aminoethoxydiphenyl borate (2-APB) exhibited the rapid and reversible inhibition of TRPM2 channels and that 2-APB inhibited heat-evoked insulin release from the pancreatic islets. 2) To clarify the involvement of TRPM2 in insulin secretion, we analyzed TRPM2 knock-out (TRPM2-KO) mice, and found that TRPM2 is involved in insulin secretion stimulated by glucose and that further potentiated by incretins, suggesting that TRPM2 may be a new target for diabetes therapy. 3) To determine the effects of a small reduction in ambient temperature on energy metabolism, we compared two groups of mice ; one exposed to a cool environment (20℃) and the other maintained in a near-thermoneutral environment (25℃) for 10 days. We found that a small reduction in ambient temperature can affect glucose homeostasis through regulation of insulin secretion and preferentially enhances fat storage in IWAT.
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