2022 Fiscal Year Final Research Report
Prevention of the vascular inury induced by glucose spike through the activation of the transcription factor Nrf2
| Project/Area Number |
20K08890
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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 | Kagoshima University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 内皮機能 |
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| Outline of Final Research Achievements |
Neither insulin resistance nor pure glucose spikes significantly deteriorated endothelial dysfunction. However, under high-glucose (20 mM) conditions, the endothelial dysfunction of thoracic aortas from insulin resistant rats subjected to glucose spikes was significantly impaired. We observed significantly enhanced DHE fluorescence as a marker of reactive oxygen species, upregulation of an oxidative stress-related gene (NOX2), and downregulation of an antioxidant gene (SOD2) in the aortas. As expected, treatment of the aorta of this group with antioxidant agents significantly improved endothelial function. We also noted that pretreatment of aortas from the same group with CDDO-Me attenuated endothelial dysfunction, accompanied by a correction of the redox imbalance, as observed in gene expression and DHE fluorescence studies.
Thus, we showed that insulin resistance and glucose spikes exert a synergistic effect on aortic endothelial dysfunction and the treatment with CDDO-Me prevent it.
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| Free Research Field |
糖尿病学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究はグルコーススパイクとインスリン抵抗性の血管内皮機能に及ぼす影響を個別に検討したものであり，グルコーススパイクは食餌誘発性肥満によるインスリン抵抗性との相乗作用によるレドックス関連遺伝子発現の不均衡化を介して，高濃度グルコースに対する血管内皮の脆弱性を増強させることを示した．さらに転写因子nrf2の活性化薬であるCDDO-Meはこの遺伝子発現の不均衡を是正し，グルコーススパイクによる血管内皮機能障害に対して保護効果を有することが明らかになった．この結果は糖尿病の大血管合併症を予防する戦略を考える上で極めて重要な示唆となると考えられた．
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