2019糖尿病口服药物治疗.ppt

治疗2型糖尿病的新型药物不断涌现 20世纪20年代2 动物胰岛素 20世纪50年代2 磺脲类、双胍类 20世纪90年代末2 格列奈类、 噻唑烷二酮类 20世纪80年代初2 人胰岛素、 α-糖苷酶抑制剂类 20世纪90年代2 胰岛素类似物 21世纪10年代2 SGLT-2抑制剂类 21世纪初2,3 GLP-1受体激动剂类、 DPP-4抑制剂类 2. 郭立新.临床药物治疗杂志.2015;13(3):18-22. 3.周映红等.中国药科大学学报.2008;39(5):385-391. * * * * DPP-4抑制剂的作用机制：GLP-1及GIP是存在于我们肠道的两种肠促胰岛激素，当摄入食物后，他们的激素水平会迅速升高1.5-3倍。GLP-1及GIP可以作用于胰腺的β细胞刺激胰岛素的分泌，GLP-1还可以作用于胰腺α细胞来抑制胰高糖素的分泌。但是他们都会迅速的被体内的DPP-4酶裂解失去活性，而DPP-4酶抑制剂可以解除这种抑制作用，从而使肠促胰素发挥血糖的调节作用。 DPP-4 Inhibitors: An Incretin-Based Glucose-Dependent Mechanism for Improving Glycemic Control This illustration shows the mechanism of action of DPP-4 inhibitors.1 DPP-4 inhibitors are believed to slow the inactivation of incretin hormones in patients with type 2 diabetes. Concentrations of the active intact hormones are increased by DPP-4 inhibition, thereby increasing and prolonging the action of these hormones.1 Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme DPP-4.1 The incretins are part of an endogenous system involved in the physiological regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic adenosine monophosphate.1 GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production.1 By increasing and prolonging active incretin levels, DPP-4 inhibitors increase insulin release and decrease glucagon levels in the circulation in a glucose-dependent manner.1 PurposeTo briefly explain the mechanism of action of dipeptidyl peptidase-4 (DPP-4) inhibitors. TakeawayDPP-4 inhibitors slow the inactivation of incretin hormones in patients with type 2 diabetes. Kieffer 1999p878, Figure 2 Ahrén 2003 p365, A,B D