2021 Fiscal Year Final Research Report
Mechanism of the regulation of insulin granule exocytosis by glutamate signaling in beta-cells
Project/Area Number |
19K09026
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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Research Institution | Kobe University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
高橋 晴美 神戸大学, 医学研究科, 特命准教授 (50546489)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | インスリン分泌 / インクレチン / グルタミン酸 |
Outline of Final Research Achievements |
Incretins are secreted from enteroendocrine cells upon meal ingestion and potentiate glucose-induced insulin secretion (GIIS) from pancreatic β-cell through cAMP signaling. We previously found that cytosolic glutamate mediates action of incretin/cAMP in insulin secretion. In this study, we aimed to elucidate the mechanisms by which glutamate mediates incretin/cAMP action in β-cell. From comparative proteomic analysis of insulin granule, candidate proteins that are possibly associated with exocytosis induced by glutamate were identified. The investigation of mechanism by which glutamine amplifies insulin secretion revealed that intracellular glutamate converted from glutamine by glutaminase amplified GIIS through elevation of intracellular Ca2+ level without further conversion to α-ketoglutarate, which is the mechanism different from previously known. These results suggest that intracellular glutamate promotes insulin secretion through multiple mechanisms in pancreatic β-cell.
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Free Research Field |
代謝内分泌学
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Academic Significance and Societal Importance of the Research Achievements |
現在、糖尿病治療において、インクレチン作用を利用したインクレチン関連薬が標準的な治療薬となっており重要な位置を占めている。本研究の成果はインクレチン関連薬の作用機序の解明に繋がることから、本治療薬の新たな可能性や治療抵抗性の症例に対しても有効な治療法の発見が期待できることから、意義は大きい。
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