胰岛素抵抗病理生理机制和治疗选择.pptVIP

* Metformin: dual sites of action Impaired insulin secretion and insulin resistance are the two key endocrine defects of type 2 diabetes. Normally, insulin acts not only to promote peripheral glucose uptake and utilisation, but also to suppress the endogenous generation of glucose production by the liver. Both of these actions of insulin are blunted in an insulin-resistant individual. Indeed, elevated hepatic glucose production is an important driver of fasting hyperglycaemia, a characteristic of type 2 diabetes. Metformin counters insulin resistance in liver and muscle, and these actions underpin the antihyperglycaemic actions of this agent. * AMPK（AMP-激活的蛋白激酶）的活性 * Metformin reduces hepatic glucose production The effects of metformin on hepatic glucose metabolism were studied in type 2 diabetic patients treated with metformin for 3 months. Metformin significantly reduced net hepatic glucose production, and the rate of gluconeogenesis, compared with baseline, while the rate of glycogenolysis was unaffected. Hundal RS, Krssak M, Dufour S et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 2000;49:2063-9. * Metformin and lipid profiles A double-blind, randomised study in 289 patients with previously diet-treated type 2 diabetes showed that total cholesterol and LDL-cholesterol improved significantly, compared with placebo, after 29 weeks of metformin treatment. Triglycerides were also reduced in the metformin group, and increased in the placebo group, though this comparison did not achieve statistical significance. These improvements in lipid profiles are typical of those observed in dyslipidaemic type 2 diabetic populations after treatment with metformin. DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin dependent diabetes mellitus. N Engl J Med 1995;333:541-9. * * Metformin: multiple mechanisms for reducing cardiovascular risk A number of other mechanisms (not all dependent on the pre