安博维与胰岛素抵抗杨文英教授ppt课件.ppt

* SLIDE 30 Metabolic changes, diabetes and atherogenesis – possible actions of irbesartan The metabolic syndrome, like the RAAS, is closely associated with atherogenesis.1 Insulin resistance is a cardinal feature of the metabolic syndrome, and may be linked to endothelial dysfunction by a variety of mechanisms. These include disturbances of signalling pathways common to insulin action and NO production, oxidative stress, hyperlipidaemia, and the secretion of hormones and cytokines by adipose tissue.2 There is growing evidence that RAAS overactivity contributes to the development of the metabolic syndrome and diabetes.3,4 One consequence of this is that RAAS-blocking agents, such as ARBs and ACE inhibitors, have consistently been found to reduce the incidence of type 2 diabetes.4 In addition, treating or delaying the progression of insulin resistance may add to the effectiveness of RAAS blockade in treating atherogenesis and preventing its complications. A variety of mechanisms have been proposed to explain how ARBs may enhance insulin function.4 These include: Improved blood flow to the skeletal muscles, thereby increasing peripheral insulin action Improved blood flow to the pancreas, thereby increasing insulin secretion Increasing the efficiency of the insulin signalling cascade Increasing the efficiency of the glucose transporter Promoting the differentiation of adipocytes, which is inhibited by angiotensin II4 Inducing peroxisome proliferator-activated receptor g (PPAR-g) – particularly in adipocytes PPAR-g is a key molecule in insulin resistance: In humans, mutations in PPARg have been reported to cause the full-blown metabolic syndrome.5 PPAR-g agonists have proven to be effective agents for the prevention and treatment of insulin resistance and type 2 diabetes.5 PPAR-g is therefore a key marker for assessing whether ARBs such as irbesartan can exert insulin sensitisation and metabolic effects. References 1. Hsueh WA, Lyon CJ, Quinones MJ. Insulin resistan