营销GLP-1作用机制.pptVIP

HL Refs Nielsen_Regul_Pept_2004_p77,79.pdf Baggio_Gastroenterology_2007_p2135.pdf DISCUSSION Exenatide is not inactivated by DPP-4 and has a much longer plasma half-life than GLP-11,2 Exenatide is the synthetic version of exendin-41 Exendin-4 and GLP-1 have equivalent binding affinities for the GLP-1 receptor in in vitro assays, and both peptides stimulate the receptor equipotently1 REFERENCES 1. Nielsen LL, et al. Regul Pept. 2004;117:77-88 2. Baggio LL, et al. Gastroenterology. 2007;132:2131-2157 * DISCUSSION: Binds to and activates GLP-1 receptors Not degraded by DPP-4, unlike GLP-1 Effect is additive to endogenous GLP-1 Metabolism and metabolites are well understood SLIDE BACKGROUND: See information about hypoglycaemia, nausea, or pancreatitis and the Important Safety Information included in this presentation, and the accompanying full Prescribing Information * DISCUSSION Summarise all points 讨论 这里比较了胰高糖素样肽1 (GLP-1)和葡萄糖依赖的促胰岛素多肽 (GIP) 的特性和生物学作用。 背景 糖尿病患者中的GLP-1分泌减少，由小肠远端和结肠释放。 GLP-1刺激胰岛素分泌，抑制胃排空，抑制胰高糖素分泌，减少进食量，减轻体重，促进β细胞量增多。 糖尿病患者中GIP分泌正常，由十二指肠释放。 GIP刺激胰岛素分泌，对胃排空的作用很小，对胰高糖素分泌没有影响，对饱胀感和体重没有调节作用，可促使β细胞量增多。 Drucker DJ. Diabetes Care. 2003;26:2929-2940. DISCUSSION Both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) play a role in glucose homeostasis after nutrient ingestion. In patients with type 2 diabetes, GIP’s action is reduced, whereas GLP-1’s action is not reduced. Therefore, GLP-1 is a more attractive therapeutic target. BACKGROUND Circulating levels of GIP are normal or slightly increased in type 2 diabetic patients in the basal or postprandial states. In contrast, subjects with diabetes or impaired glucose tolerance exhibit modest but significant reductions in levels of circulating GLP-1. Meal-induced increases in GIP and GLP-1 secretion are inversely correlated with the extent of insulin resistance detected in human subjects. The lower levels of circulating GLP-1 detected in diabetic subjects are not att