2014 Fiscal Year Final Research Report
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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| Keywords | 糖尿病 / インスリン分泌 / 分泌顆粒 |
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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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| Free Research Field |
糖尿病
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