胰岛素增敏剂的合理应用ppt课件.pptVIP

* This slide summarises the action of PPAR?-agonist binding in adipose tissue. Binding of a PPAR? agonist, such as rosiglitazone, to PPAR? produces changes in the synthesis of a number of important proteins. The major metabolic effects are increased glucose uptake and reduced release of FFAs. PPAR? plays a major role in the storage of FFAs in adipose tissue by stimulating lipolysis of circulating triglycerides and subsequent uptake of FFAs into adipocytes. Extracellular triglycerides cannot be directly transported into adipocytes, hence the initial step in transportation involves lipolysis of triglyceride through the action of lipoprotein lipase (LPL), a hydrolytic enzyme present in adipose tissues. The action of LPL releases FFAs, which enter the adipocyte by a process involving fatty acid transport protein (FATP). Finally, within the adipocyte, FFAs are converted into triglycerides in a series of steps involving the enzyme acetyl-CoA synthase (ACS). Arner P. Diabetes Obes Metab 2001; 3 (Suppl 1): S11–9. * * 在组织水平，胰岛素抵抗的结局包括肝脏、脂肪组织和肌肉中胰岛素依赖的葡萄糖摄入降低。 肝脏过量葡萄糖的生成，导致了高血糖。脂肪组织甘油三酯的过量的分解，导致了循环游离脂肪酸的浓度增加。 而更为重要的，不仅在代谢过程中游离脂肪酸与葡萄糖的代谢相互竞争，而且不断增加的证据也证实了升高的游离脂肪酸对胰腺有毒性，除此之外还促进了肝脏葡萄糖的释放。 The consequences of insulin resistance at the tissue level include decreased insulin-dependent glucose uptake into liver, adipose tissue and muscle. This, combined with excessive glucose production by the liver, leads to hyperglycemia. In addition, excessive breakdown of triglycerides in the adipose tissue leads to increased circulating free fatty acids. This is particularly important since not only do free fatty acids compete for glucose during metabolism, but there is also increasing evidence that elevated free fatty acids are toxic to the pancreas. DeFronzo RA, Bonadonna RC Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care 1992; 15:318–368. * 机制： 1。肾小球系膜细胞存在PPAR，文迪雅激活PPAR 后，抑制肾小球系膜细胞的增生，改善肾功能，减少微量白蛋白尿 2。独立血糖控制之外的作用 * 机制： 1。肾小球系膜细胞存在PPAR，文迪雅激活PPAR 后，抑制肾小球系膜细胞的增生