RISS 검색 - 국내학술지논문 상세보기

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다국어 초록 (Multilingual Abstract)

Purpose: Insulin resistance and reactive oxygen species (ROS) have been reported to play essential pathophysiological roles in cardiovascular disease. The relationship between insulin resistance and oxidative stress in vasculature remains unclear. Angiotensin Ⅱ, a potent vasoconstrictor and hypertrophic inducer of vascular smooth muscle cells (VSMCs), increases the production of ROS in VSMCs. H₂O₂ inhibits Akt/PKB phosphorylation, insulin receptor binding and receptor autophosphorylation in VSMCs. Exposure to H₂O₂ resulted in impaired insulin-stimulated glucose transport and GLUT4 translocation without affecting insulin-induced P13-kinase activation. Angiotensin Ⅱ-induced insulin resistance did not impair early insulin-signaling steps. Angiotensin Ⅱ may be induce impairment of insulin signaling located down from PI3K. The study was conducted to assess whether oxidative stress induces vascular insulin resistance in OLETF rats, a model of type 2 diabetes.
Subjects and methods: We used OLETF rats (20/40 weeks, 5/5), as a model of type 2 DM, and LETO rats (20/40 weeks, 5/5) as a control. Aortas of each rats were extracted. Superoxide production levels were measured by NBT assay, Lucigenin assay. The glucose uptake of aorta was measured by 2-deoxyglucose uptake. The expressions of IRS-1, PI3K, Akt/PKB were detected by immunoprecipition or immunoblotting.
Results: Superoxide production was significantly increased in aorta of OLETF rats compared with controls. Aorta of OLETF rats exhibited decreased IRS-1 content, and increased phosphorylation of IRS-1 at Ser307 compared with LETO rats. There were no significant differences in the expressions of PI3K, and Akt/PKB between two groups.
Conclusions: These findings suggest that oxidative stress induces insulin resistance in vasculature of OLETF rats specifically through increasing serine phosphorylation of IRS-1 and its degradation by a proteosome-dependent pathway, providing an alternative mechanism that may explain the association with insulin resistance and diabetic vascular complications.