2013 Fiscal Year Final Research Report
Regulation of glucose and incretin-stimulated insulin secretion by cAMP-EPAC2-TRPM2
| Project/Area Number |
24890219
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Metabolomics
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2012-08-31 – 2014-03-31
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| Keywords | 糖尿病 / インスリン分泌 / インクレチンホルモン |
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| Research Abstract |
In pancreatic beta-cells, closure of ATP-sensitive-K+ (K-ATP) channel is an initial process triggering glucose-stimulated insulin secretion. However theoretically, closure of K-ATP channel alone should be insufficient to shift membrane potential toward threshold level to set on insulin secretion. Opening of background nonselective-cation channels (NSCCs) facilitates excitability of the membrane. We here show that a class of NSCC is activated by both glucose and incretin hormones, GLP-1 and GIP, via cAMP/EPAC-mediated NSCC (TRPM2 channel) pathway. Our data demonstrate that glucose metabolism leads to opening of TRPM2 channel and closure of K-ATP channel simultaneously. Glucose- and incretin-activated NSCC works in concert to effectively induce membrane depolarization to initiate insulin secretions. The present study reveals a newly confirmed beta-cell mechanism through which glucose and incretin evoke insulin secretion and provides a innovative target to treat type 2 diabetes.
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[Journal Article] Involvement of cAMP-EPAC-TRPM2 activation in glucose- and incretin-induced insulin secretion2014
Author(s)
Yoshida M, Dezaki K, Uchida K, Kodera S, Lam NV, Ito K, Rita RS, Yamada H, Shimomura K, Ishikawa SE, Sugawara H, Kawakami M, Tominaga M, Yada T, Kakei M.
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Journal Title
Peer Reviewed
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