2021 Fiscal Year Final Research Report
Elucidation of the regulatory mechanism of GLP-1 secretion by carbonic anhydrase 8 (Car8)
| Project/Area Number |
19K08977
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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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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | インクレチン分泌 / GLP-1 / CAR8 |
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| Outline of Final Research Achievements |
Car8 gene expression in isolated L cells was significantly higher than in non-L cells, and immunostaining of mouse lower small intestine also confirmed Car8 expression in L cells. GLP-1 secretion from STC-1 cells upon stimulation with LCFAｓ was enhanced by suppression of Car8 expression and decreased by overexpression. Furthermore, the increase in intracellular calcium concentration in STC-1 cells upon α-linolenic acid stimulation was increased by suppression of Car8 expression. GLP-1 secretion in mutant mice lacking CAR8 function was similar to that of wild-type mice upon oral glucose loading, but GLP-1 secretion upon corn oil administration was significantly higher than that of wild-type mice. These results suggest that CAR8 is involved in the regulation of LCFA-induced GLP-1 secretion.
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| Free Research Field |
インクレチン研究
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| Academic Significance and Societal Importance of the Research Achievements |
Car8を介したGLP-1分泌制御機構を明らかにすることにより、内因性GLP-1分泌を増強する薬剤の開発につながる可能性があり、糖尿病治療の新たな標的となりうると考えている。L細胞が標識されたマウスや、単離腸管内分泌細胞の確立した解析技術を併せ持つ研究室は世界的に見ても限られており、また中枢神経系以外の細胞・組織におけるCar8の発現・機能に関しては全く報告がなく、本研究の独自性は極めて高いといえる。さらに本研究での解析手法や知見が、他の腸管内分泌ホルモンの分泌・作用機構も含めた腸管内分泌システムの統合的理解への端緒となりうるため、より広い領域への波及効果も期待できる。
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