| Summary: | 碩士 === 國立成功大學 === 物理治療研究所 === 94 === Background and purpose: Obesity is a potential medical problem that has been considered closely associated with insulin resistance. Insulin and insulin-like growth factor-1(IGF-1) play an important role in the regulation of cardiovascular function, and have vasorelaxant effects in vivo that depend on the production of nitric oxide (NO). The signaling pathways of insulin and IGF-1 are initiated through the insulin receptor (IR) and/or IGF-1 receptor (IGF-1R) to lead to phosphorylation of adaptor protein, insulin receptor substrate-1(IRS-1), and further to activate phosphatidylinositol-3 kinase (PI3K). This increases the activity of nitric oxide synthase (NOS), and then induces NO production. Moreover, it is well known that moderate exercise improves acetylcholine-induced vasorelaxation by increasing NO production. However, few studies have investigated the effects of exercise intervention on the vascular function mediated by insulin and IGF-1. Thus, the aim of this study was to investigate the effects of moderate exercise on vasorelaxant responses mediated by insulin and IGF-1 in aortas of obese rats. Methods: Obese Zucker rats and age-matched lean Zucker rats were randomly divided into sedentary and exercise groups; i.e., obese sedentary (OS), obese with exercise (OE), lean sedentary (LS), and lean with exercise (LE) groups. The exercise groups ran on a treadmill five days a week for a period of 12 weeks in total. In contrast, the sedentary groups were regularly placed on the treadmill for similar periods of time. At the end of the experiments, the thoracic aortas of rats were isolated for the analyses of vasorelaxation and immunohistochemistry. Results: We found that, (1) compared with that in aortas of lean rats, the insulin-induced vasorelaxation was significantly decreased in obese rats, whereas the IGF-1-induced vasorelaxation was significantly increased in obese rats; (2) moderate exercise significantly ameliorated insulin-induced vasorelaxation in obese rats, but did not induce significant change in lean rats. In contrast, this exercise significantly increased IGF-1-induced vasorelaxation in lean rats, but did not induce any change in obese rats.; (3) the exercise effects on vasorelaxation were mediated by the altered release of PI3K and NOS; (4) there was no significant difference in the sodium nitroprusside (SNP, a NO donor)-induced vasorelaxation among the four groups; (5) immunohistochemical analysis showed that, compared with that in lean rats, the protein expression of IR and IRS-1 significantly decreased, but IGF-1R significantly increased in the endothelium and vascular smooth muscle in aortas of obese rats. After the exercise intervention, the protein expression of IR and IRS-1 significantly increased in obese rats, and IGF-1R significantly increased in lean rats. Conclusion: Obesity would induce a significant decrease of the insulin-mediated vascular function and IGF-1 might play a compensatory role for it. Also, the intervention of moderate exercise could have positive effects on the amelioration of cardiovascular function in the obesity.
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