Deacon Carolyn F
Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Diabetes Obes Metab. 2007 Sep;9 Suppl 1:23-31. doi: 10.1111/j.1463-1326.2007.00765.x.
Incretins are gut peptides that potentiate nutrient-stimulated insulin secretion following meal ingestion. Activities of the dominant incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, include glucose-dependent stimulation of insulin secretion and, in preclinical models, improvement in islet beta-cell mass. GLP-1 additionally reduces glucagon secretion, inhibits gastric emptying and promotes satiety. Patients with type 2 diabetes mellitus (T2DM) exhibit reduced total and intact GLP-1 levels, and exogenous administration of the hormone via continuous infusion results in glucose profiles similar to those in non-diabetic subjects. Incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). Thus, strategies to enhance incretin activity have included development of GLP-1 receptor agonists resistant to the action of DPP-4 (e.g. exenatide and liraglutide) and DPP-4 inhibitors that act to increase concentrations of endogenous intact incretins (e.g. sitagliptin and vildagliptin). Clinical trials of these incretin-based therapies have shown them to be effective in improving glycaemic control in patients with T2DM.
肠促胰岛素是一类肠道肽，在进食后可增强营养物质刺激的胰岛素分泌。主要的肠促胰岛素，即胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性促胰岛素多肽，其作用包括葡萄糖依赖性刺激胰岛素分泌，并且在临床前模型中可改善胰岛β细胞量。GLP-1还可减少胰高血糖素分泌、抑制胃排空并促进饱腹感。2型糖尿病（T2DM）患者的总GLP-1水平和完整GLP-1水平均降低，通过持续输注外源性给予该激素可使血糖水平类似于非糖尿病受试者。肠促胰岛素会被二肽基肽酶-4（DPP-4）迅速降解。因此，增强肠促胰岛素活性的策略包括开发对DPP-4作用具有抗性的GLP-1受体激动剂（如艾塞那肽和利拉鲁肽）以及可增加内源性完整肠促胰岛素浓度的DPP-4抑制剂（如西格列汀和维格列汀）。这些基于肠促胰岛素的疗法的临床试验表明，它们可有效改善T2DM患者的血糖控制。
