Potentiation of Glucose-Stimulated Insulin Secretion by GPR40-PLC-TRPC Pathway and cAMP-EPAC2-TRPM2 Pathway in Pancreatic Beta Cells
| Project/Area Number |
26870532
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Endocrinology
Metabolomics
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 膵β細胞 / インクレチン / ＧＰＲ４０ / ＧＬＰ－１ / Ｔｒｐｍ２ / ＴｒｐＣ３ / Trpm2 / TrpC3 / グレリン / GPR40 / Trpm2チャネル / ＥＰＡＣ / アドレナリン / インスリン分泌 |
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| Outline of Final Research Achievements |
It has been proposed that glucose-stimulated insulin secretion is initiated by closure of KATP channels, followed by membrane depolarization. In theory, however, closure of KATP channels is insufficient to shift the membrane potential toward a threshold level, since membrane potential is determined by the overall balance between outward and inward currents. Modest constitutional opening of background inward current through nonselective cation channels (NSCCs) is crucial to facilitate depolarization. Recently, we demonstrated that a class of NSCC is activated by both glucose metabolism and incretin hormones, via Trpm2 pathway. In this study, we demonstrate that gastric hormone ghrelin attenuates glucose-induced insulin secretion via TRPM2 pathway. We also demonstrate that GPR40 agonist stimulate insulin secretion via the TRPC3 channel pathway. We believe that TRPM2 pathway and TRPC3 pathway provide a potential therapeutic target for the treatment of type 2 diabetes.
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] The beta-cell GHSR and downstream cAMP/TRPM2 signaling account for insulinostatic and glycemic effects of ghrelin.2015
Author(s)
Kurashina T, Dezaki K, Yoshida M, Sukma Rita R, Ito K, Taguchi M, Miura R, Tominaga M, Ishibashi S, Kakei M, Yada T
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Journal Title
Sci Rep
Volume: 5
Issue: 1
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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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
Diabetes
Volume: (Epub ahead of print)
Issue: 10
Pages: 3394-3403
DOI
NAID
Related Report
Peer Reviewed / Open Access
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