2011年研究生讲座糖尿病治疗新理念.ppt-[自动保存的].pptVIP

手术治疗肥胖的2型糖尿病 * 肠道糖吸收，促进了肠促胰岛素的分泌，而高碳水化合物饮食更能增加GLP-1释放。肠促胰岛素对A细胞和B细胞都有作用，促进胰岛素分泌，抑制胰高糖素的释放，对这两种激素起着重要的平衡作用。 * 2型糖尿病的产生是由于β细胞功能的衰竭以及在外周脂肪、肌肉以及肝脏中胰岛素抵抗的存在。 不同的口服降糖药有着不同的作用机制以及作用的靶器官/组织。 * 胰岛素治疗的目的在于模拟生理性胰岛素释放：基础＋餐时胰岛素。 * 基于此，第68届Banting奖获得者DeFronzo教授提出：2型糖尿病治疗方案的选择应该基于已知的病因，纠正病理生理缺陷，而不是简单的降低糖化血红蛋白。 因此，从单一糖化血红蛋白降低策略到全面风险降低策略是目前糖尿病治疗的新理念，纠正病生理缺陷，尤其是胰岛素抵抗是糖尿病治疗的关键。 * * * 胰岛功能异常包括B细胞异常，使胰岛素分泌障碍，也包括α细胞异常，使胰高糖素分泌增多，是双激素缺陷。这种异常在IGT和疾病早期就已经发现 * Fig. 3. Proposed mechanisms of intraislet insulin suppression of glucagon secretion. Insulin secreted from -cells acts in a paracrine manner to activate the insulin-signaling cascade in -cells. This has 3 main consequences: 1) activation of KATP channels, 2) enhancement of type A GABA receptor (GABAAR)- mediated GABA current, and 3) inhibition of proglucagon gene transcription. First, insulin decreases the -cell KATP channel sensitivity to ATP inhibition in a phosphatidylinositol 3-kinase-dependent manner, causing an increase in the efflux of K ions from the -cell and hyperpolarizing the -cell membrane potential. The resultant cessation of action potentials prevents an increase in cytosolic [Ca2] and inhibits glucagon secretion. Second, activation of the insulin receptor (IR) promotes membrane translocation of GABAAR and enhances GABA-mediated Cl influx. The -cell membrane potential becomes hyperpolarized, and glucagon secretion is suppressed. Finally, insulin inhibits proglucagon gene transcription, possibly representing a long-term mechanism for regulating -cell function. Other modulators of -cell glucagon secretion, including Zn2 and somatostatin, are not shown. * 只讲肝脏的作用。 ⊕ * * * Insulin secretion from the pancreas normally reduces glucose output by the liver, enhances glucose uptake by skeletal muscle, and suppresses fatty acid release from fat tissue.1 The various factors shown in the red box that contribute to the pathogenesis of type 2 diabetes affect both insulin secretion and insulin action.1 Decreased insulin secreti