diabetes概要.ppt

* * * * * * * * 肠促胰岛激素是一种胃肠道激素，是对摄食反应所释放的一种激素，其中最重要的是胰高糖素样多肽1(GLP-1)和葡萄糖依赖性促胰岛素多肽（GIP），前者是由远端消化道（回肠和结肠）的L细胞合成，后者是由近短消化道（十二指肠）的K细胞合成. GLP-1 和 GIP 是两种主要的肠促胰岛素，在营养素被吸收到体内时胰岛素反映方面扮演了重要角色. GLP-1除了在血糖升高时可以刺激胰岛素分泌，还可以抑制胰高糖素分泌. 这些作用都是高度葡萄糖依赖性的.3 在健康志愿者中, 当给予 GLP-1, 使其水平超过生理输出时，观察到明显的剂量依赖性的抑制胃排空的作用.I在体外研究和啮齿类动物体内研究、以及分离人胰岛研究中, GLP-1 显示可以通过促进增殖和抑制凋亡使beta细胞体积增加. GIP同样也刺激葡萄糖依赖性的胰岛素反应, 但是它并不影响胃排空. 当对2型糖尿病患者给予超过生理量的GIP时，GIP的促胰岛素活性弱于在正常人中所观察到的水平. GIP 并未观察到影响饱腹感或体重的作用. 在胰岛细胞系，GIP已经显示出有促进beta细胞增殖和存活的作用. GLP-1 and GIP are the currently identified incretin hormones. An incretin is a hormone with the following characteristics1,2: - It is released from the intestine in response to ingestion of food, particularly glucose. - The circulating concentration of the hormone must be sufficiently high to stimulate the release of insulin. - The release of insulin in response to physiological levels of the hormone occurs only when glucose levels are elevated (glucose-dependent). GIP and GLP-1 are hormones that fulfill these 3 characteristics, qualifying them as incretins.2 In the fasting state, GIP and GLP-1 circulate at very low levels. Their levels rapidly increase after food ingestion and play a role in the release of insulin.3,4 GLP-1 stimulates insulin response from β cells in a glucose-dependent manner and suppresses glucagon secretion from α cells in a glucose-dependent manner. GIP also potentiates insulin release from β cells in a glucose-dependent manner.5 Other effects of GLP-1 and GIP are summarized on the slide. References 1. Creutzfeldt W. The [pre-] history of the incretin concept. Regul Pept. 2005;128:87–91. 2. Creutzfeldt W. The entero-insular axis in type 2 diabetes – incretins as therapeutic agents. Exp Clin Endocrinol Diabetes. 2001;109(suppl 2):S288-S303. 3. Gautier JF, Fetita S, Sobngwi E, Salaün-Martin C. Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. Diabetes Metab. 2005;31:233–242. 4. Holst JJ, Gromada