合理应用抗糖尿病药物课件.ppt

讨论 葡萄糖依赖的促胰岛素多肽 (GIP)和胰高糖素样肽1 (GLP-1)是两种肽类激素，负责营养素刺激下胰岛素分泌的绝大部分。 GLP-1引起大部分的肠促胰素效应，而GIP负责β细胞功能肠促胰素效应的约20%-30%。 GLP-1主要由位于回肠和结肠的 L细胞和合成和释放，少部分在十二指肠和空肠合成和释放。 GIP 由肠道 K细胞合成和释放，这种细胞主要位于十二指肠和近端空肠。 背景 虽然肠促胰素效应最早于 1960年代就得到了证实，但大约过了 15-20年后，才鉴定出GIP和GLP-1这两种成分。 GIP和GLP-1是胰高糖素肽超家族的成员，具有相当多的相同氨基酸成分。 进餐后分泌有两种GLP-1形式，GLP-1 (7-37)和GLP-1(7-36)酰胺，这两种成分只有1个氨基酸的差别。 这两种肽是等效的，血浆半衰期相同，生物活性也相同，都作用于相同的受体；但是血液循环中有活性的GLP-1的绝大部分(80%)似乎是GLP-1 (7-36)酰胺。 * DISCUSSION Exenatide (exendin-4) is the synthetic version of salivary protein found in the Gila monster Position 2 of the amino acid sequence is different between glucagon-like peptide 1 (GLP-1) and exenatide, making exenatide resistant to dipeptidyl peptidase-4 (DPP-4) enzymatic degradation BACKGROUND Exendin-4 is a naturally occurring incretin hormone in the Gila monster Heloderma suspectum Gila monsters produce exendin-4, which is a separate and distinct protein compared to human GLP-1 Exendin-4 mimics some of the actions of GLP-1 in vivo Exendin-4 exerts some of its antidiabetic actions via unknown mechanisms * * HL Refs Toft-Nielsen_J_Clin_Endocrinol_Metab_2001_p3720.pdf Fehse_J_Clin_Endocrinol_Metab_2005_p5991,5992,5993,5994.pdf Kolterman_J_Clin_Endocrinol_Metab_2003_p3082,3082,3086.pdf Amylin_ise_2993_Table 14_FPG_wk30.pdf Amylin_ise_2993_SDS 5.5_PPG_meal_test.pdf Amylin_ise_2993_SDS 5.8_PPG_LS mean diff.pdf Linnebjerg_Regul_Pept_2008_p11.pdf DISCUSSION In patients with type 2 diabetes, exenatide Increases first- and second-phase insulin response1 Increases in insulin response were: AUC0-10 min, 310%; AUC10-120 min, 270%; AUC0-120 min, 270% Increases in C-peptide response were: AUC0-10 min, 200%; AUC10-120 min, 180%; AUC0-120 min, 180% Suppresses inappropriately elevated glucagon secretion2 Delayed increased gastric half-emptying time for a solid meal3 Lowered PPG and FPG concentrations4 Reductions from baseline (difference from placebo) were 75 to 80 and 20 to 23 mg/dL, respectively Reduced 24-hour blood glucose profiles