2021 Fiscal Year Final Research Report
Murine remote ischemic preconditioning suppresses diabetic ketoacidosis by enhancing glycolysis and entry into tricarboxylic acid cycle in the liver with upregulation of hepatic glucose transporter-4
| Project/Area Number |
19K07483
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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 49030:Experimental pathology-related
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| Research Institution | Kochi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
柿沼 由彦 日本医科大学, 大学院医学研究科, 大学院教授 (40233944)
井上 啓史 高知大学, 教育研究部医療学系臨床医学部門, 教授 (00294827)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 糖代謝 / 肝臓 / 副交感神経 / 虚血再灌流モデル / エネルギー産生 / クエン酸回路 |
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| Outline of Final Research Achievements |
Hindlimb ischemia-reperfusion (IR) activated the brainstem neurones in the central parasympathetic nervous system and decreased BS levels by downregulating hepatic gluconeogenesis and upregulating glucose uptake. The overexpression of GLUT4 on the membrane peripheries contributed to increasing glucose uptake found in IR-treated livers. This acceleration of glucose uptake via GLUT4 may induce marked glycogen storage. These results indicated that in the IR-treated diabetic liver, energy production was promoted through acceleration of the tricarboxylic acid cycle linked with increased glucose preference rather than fatty acid under feeding conditions. Indeed, serum ketone body levels were significantly suppressed by IR. It is plausible that IR may offer a beneficial therapeutic modality for controlling diabetic hyperglycemia and ketoacidosis.
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| Free Research Field |
病理学
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| Academic Significance and Societal Importance of the Research Achievements |
後肢虚血・再潅流刺激は血圧測定マンシェットを巻く程度の極めて侵襲性の少ない手技であり、元来、心筋の虚血に対する臓器保護性の観点より研究が進んできた分野である。我々は、その過程で糖代謝因子の発現亢進を伴う点に着目し、後肢虚血・再潅流刺激が副交感神経中枢・迷走神経を介し、肝において糖新生抑制およびインスリン非依存性の糖取り込み亢進による血糖低下をもたらし、糖を基質としたエネルギー産生を促進して血中ケトン体の低下をももたらすことを示した。このことは後肢虚血・再潅流刺激が糖尿病において、血糖低下効果をもたらすのみならず、その合併症の抑制をももたらす可能性を示唆しており意義あるものと考える。
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