Investigation of the biological effects of the polyphenol resveratrol on insulin producing and insulin target tissues

多酚是葡萄皮中含有的化合物，在红酒中含量很高。许多研究表明，多酚具有多种有益健康的作用，包括预防癌症和心血管疾病。胰岛素是一种激素，在调节血糖水平方面起着重要作用。当血糖水平升高时，胰岛素由胰腺释放，并通过血液作用于肝细胞，抑制葡萄糖的产生和释放，同时作用于肌肉细胞，使它们从血液中摄取葡萄糖。这些胰岛素作用的净效果是使血糖水平恢复正常。胰岛素抵抗加上胰腺功能下降导致2型糖尿病。血液中游离脂肪酸的升高，就像肥胖一样，已经被证明会导致胰岛素抵抗和胰腺损伤。我们和其他人的研究表明，多酚具有抗糖尿病的特性。我们研究项目的长期目标是确定多酚对肌肉、肝脏和胰腺细胞的影响。这些目标将通过培养细胞和动物（大鼠）体内的细胞来解决。今后5年的研究重点将放在多酚白藜芦醇上。我们的假设是，多酚作用于骨骼肌细胞和肝细胞以防止胰岛素抵抗，并作用于胰腺细胞以恢复胰岛素分泌。这些研究将帮助我们了解白藜芦醇在葡萄糖稳态中的作用，并确定其在治疗胰岛素抵抗状态（如2型糖尿病）中的潜力。

Polyphenols are compounds found in the skin of grapes and in high concentration in red wine. Many studies have shown that polyphenols have various beneficial health effects including protection against cancer and cardiovascular disease.  Insulin is a hormone that plays a major role in regulating the blood glucose levels. When the blood glucose levels are increased, insulin is released by the pancreas and through the bloodstream acts on liver cells inhibiting glucose production and release as well as on muscle cells causing them to take up glucose from the blood. The net effect of these insulin actions is to bring the blood glucose levels back to normal. Resistance to insulin in combination with decreased pancreatic function leads to type 2 diabetes. Elevated free fatty acids in the blood, as seen in obesity, have been shown to cause insulin resistance and pancreatic impairment.Work by our group and others indicates that polyphenols have antidiabetic properties. The long-term goals of our research program are to determine the effects of polyphenols on muscle, liver and pancreatic cells. These goals will be addressed using cells in culture and animals (rats) in vivo. The focus of our research for the next five years will be on the polyphenol resveratrol. Our hypothesis is that polyphenols act on skeletal muscle cells and liver cells to prevent insulin resistance and on pancreatic cells to restore insulin secretion. These studies will help us to understand the role of resveratrol in glucose homeostasis and to determine its potential in the treatment of insulin resistant states such as type 2 diabetes.