The Effect of Alpha Lipoic Acid on Insulin Resistance, Oxidative

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  • 조회 279
  • 작성자 이태화
  • 2014-01-17



The Effect of Alpha Lipoic Acid on Insulin Resistance, Oxidative stress and Vascular Complication   


- Date/Time : Thu March 6., 2003


- Speaker : 이인규 교수

            - 계명대학교 의과대학  

- Place : Life Science Bldg. #104

- For inquires : Professor Gou Young Koh Dept. of Life Science

           생명과학과 고규영 교수 (☎279-2286)


- Abstract

  Insulin resistance is associated with multiple risk factors for atherosclerosis, including obesity, diabetes, hypertension, and dyslipidemia. Clustering of these risk factors in metabolic syndrome profoundly elevates the risk of myocardial infarction.2 However, the mechanisms by which atherosclerosis is accelerated among patients with metabolic syndrome remain inadequately defined. Recently, increased oxidative stress has been proposed as a major cause of vascular complications of patients with Insulin resistance. Endothelial dysfunction is commonly found in subjects with obesity and insulin resistance, and is considered a prerequisite for atherosclerosis. Increased generation of oxygen free radicals in patients with Insulin resistance could deplete cellular antioxidants and inactivate endothelial dependent vasodilating factor (EDRF), such as nitric oxide (NO).  The purpose of this study was to evaluate whether the antioxidant  -lipoic acid (ALA) is effective in endothelial dysfunction of brachial artery, which induced by increased oxidative stress in postmenopausal diabetic women using high resolution ultrasound technique and initial reaction time (IRT) measurement , We enrolled 11 menopaused women (mean age, 56.5 5.1 years) with uncomplicated type 2 diabetes. All patients were taking 1200 mg of ALA. We measured of superoxide anion (O2-) in neutrophils as a marker of oxidative stress. Flow-mediated dilation (FMD) was measured using a high-resolution ultrasound. After treatment of ALA, fasting blood glucose was decreased significantly, the endothelium-dependent vasodilation of the brachial artery was increased, and O2- production was also decreased significantly.   Additionaly, excessive proliferation of vascular smooth muscle cells (VSMC) and neointimal formation are critical steps in the pathogenesis of atherosclerosis and restenosis following percutaneous transluminal angioplasty. Of all, the transcription factor NF-kB, which is an important and redox sensitive transcription factor, plays a critical role in the activation of several genes, involved in cell-cycle regulation, as well as cytokines related with vascular smooth muscle cell proliferation. Well-known-antioxidant, alpha-lipoic acid has shown many advantages in patient with diabetes including improvement of painful neuropathy, glucose intolerance as well as endothelial dysfunction , through normalization of NF-kB activation. In this study, we showed that alpha-lipoic acid treatment can inhibit vascular smooth muscle cell proliferation, migration in vitro as well as neointimal formation in vivo through the inhibition of NF-kB activation . In conclusion, our results demonstrated that treatment of alpha-lipoic acid is very valuable to improve endothelial dysfunction, and to inhibit VSMC proliferation, neointimal formation as well as prevention of other vascular complication in patients with Insulin resistance.