GLP与DPP.ppt

2型糖尿病患者肠促胰素效应明显减弱。 * * * GLP-1有着多种重要的生理作用 * * PCP slide kit Post-Paris Draft 1 * GLP-1主要是针对胰岛的α和β双细胞发挥作用，从而抑制血糖升高。 对于β细胞，GLP-1能够改善β细胞的功能和β细胞的量，从而葡萄糖浓度依赖性的促进胰岛素的合成和分泌。 对于α细胞，GLP-1则通过直接和间接作用葡萄糖浓度依赖性的抑制胰高糖素分泌，从而降低血糖。 2型糖尿病晚期，患者的β细胞功能严重受损，GLP-1促进胰岛素分泌的作用很弱，仅通过抑制胰高糖素分泌发挥部分降糖作用。因此，尽早应用GLP-1类药物可以带来更多获益。 * The presence of nutrients in the gastrointestinal tract rapidly stimulates the release of incretins: GLP-1 from L cells located primarily in the distal gut (ileum and colon), and GIP from K cells in the proximal gut (duodenum).1,2 Collectively, these incretins exert several beneficial actions, including stimulating the insulin response in pancreatic beta cells and reducing glucagon production from pancreatic alpha cells when glucose levels are elevated in a glucoxse dependent manner.3,4 Increased insulin levels improve glucose uptake by peripheral tissues; the combination of increased insulin and decreased glucagon reduces hepatic glucose output.5 The incretins are rapidly inactivated by the dipeptidyl peptidase 4 (DPP-4) enzyme.?? Patients with type 2 diabetes have a diminished incretin effect as a consequence?of reduced GLP-1 levels3 and reduced GIP effect.3?Preventing the degradation? of the incretins by?inhibiting DPP-4 enhances the level of active incretins.3 This in turn enhances the body’s own ability to control glucose.? ? References Brubaker PL, Drucker DJ. Minireview: Glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology 2004;145:2653–2659. Zander M, Madsbad S, Madsen JL et al. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and β-cell function in type 2 diabetes: A parallel-group study. Lancet 2002;359:824–830. Ahrén B. Gut peptides and type 2 diabetes mellitus treatment. Curr Diab Rep 2003;3:365–372. Drucker DJ. Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology 2002;122:531–544. Buse JB, Polonsk