Investigation of molecular mechanism of glucose- and incretin-stimulated insulin secretion
| Project/Area Number |
24591325
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 糖尿病 / インスリン分泌 / 分泌顆粒 / グルコース応答性 / インクレチン応答性 / インスリン分泌顆粒 / AKAP / PKA / プロテインキナーゼA / インクレチン |
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| Outline of Final Research Achievements |
We examined the role of SPHKAP in glucose- and exendin-4-stimulated insulin secretion. Quantitative real-time PCR and western blot showed that SPHKAP was highly expressed in beta-cells. Immunoprecipitation showed that SPHKAP interacted with PKA-RI subunit but not with PKA-RII subunit in SPHKAP-overexpressed HEK293 and INS-1D cells. Immunohistochemical staining revealed that SPHKAP was localized in beta-cells and not in alpha-cells of islets from Wistar rats, C57BL/6 mice and human. Confocal microscopy and electron microscopy analysis clarified that SPHKAP was co-localized with insulin secretory granules. Overexpression of SPHKAP decreased glucose-stimulated insulin secretion by about 50% and exendin-4-stimulated insulin secretion by about 35%. Knock down of endogenous SPHKAP resulted in about 1.5-fold increase in glucose- and exendin-4-stimulated insulin secretion. These results demonstrate that SPHKAP is localized on insulin secretory granules, and inhibits insulin secretion.
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Report
(4 results)
Research Products
(58 results)
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[Journal Article] Lack of Goal Attainment Regarding the Low-density Lipoprotein Cholesterol Level in the Management of Type 2 Diabetes Mellitus2013
Author(s)
Hosokawa M, Hamasaki A, Nagashima K, Harashima S, Toyoda K, Fujita Y, Harada N, Nakahigashi Y, Fujimoto S, Inagaki N.
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Journal Title
Internal Medicine
Volume: 52
Issue: 21
Pages: 2409-2415
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed
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[Journal Article] Self-monitoring of blood glucose (SMBG) improves glycaemic control in oral hypoglycaemic agent (OHA)-treated type 2 diabetes (SMBG-OHA study)2013
Author(s)
Harashima S, Fukushima T, Sasaki M, Nishi Y, Fujimoto S, Ogura M, Yamane S, Tanaka D, Harada N, Hamasaki A, Nagashima K, Nakahigashi Y, Seino Y, Inagaki N
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Journal Title
Diabetes Metab Res Rev
Volume: 29(1):77-84
Issue: 1
Pages: 77-84
DOI
Related Report
Peer Reviewed
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[Journal Article] Efficacy and safety of switching from basal insulin to sitagliptin in Japanese type 2 diabetes patients.2013
Author(s)
Harashima SI, Tanaka D, Yamane S, Ogura M, Fujita Y, Murata Y, Seike M, Koizumi T, Aono M, Wang Y, Inagaki N.
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Journal Title
Horm Metab Res.
Volume: 45(3)
Issue: 03
Pages: 231-238
DOI
NAID
Related Report
Peer Reviewed
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