Clinical Diabetes Programs, University of Southern California, Los Angeles, California, USA.
Am J Med. 2010 Mar;123(3 Suppl):S28-37. doi: 10.1016/j.amjmed.2009.12.007.
Incretin hormones are secreted in response to food ingestion and help manage glycemic control by regulating insulin and glucagon release, slowing gastric emptying, and reducing caloric intake. Glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, secreted from the L-cells of the lower gut and K-cells of the intestines, respectively, are responsible for these incretin effects, which are reduced in patients with type 2 diabetes mellitus. Initially, the rapid degradation of either incretin by dipeptidyl peptidase-4 (DPP-4) complicated the development of viable therapeutics based on either hormone. However, the US Food and Drug Administration (FDA) has approved 2 incretin-based therapies in which their mechanisms of action augment or amplify the effects of naturally occurring GLP-1. Exenatide, a first-in-class GLP-1 receptor agonist, exhibits the same mechanisms of action as native GLP-1. Sitagliptin inhibits the DPP-4 enzyme, thus increasing the half-life of endogenous GLP-1. This review examines data from recent GLP-1 receptor agonist and DPP-4 inhibitor studies in patients with type 2 diabetes, as well as data on other incretin-based therapies in clinical development.
肠促胰岛素激素在进食后分泌，通过调节胰岛素和胰高血糖素的释放、减缓胃排空和减少热量摄入来帮助控制血糖。分别由下消化道的 L 细胞和肠道的 K 细胞分泌的胰高血糖素样肽-1 (GLP-1)和葡萄糖依赖性胰岛素释放肽负责这些肠促胰岛素作用，而这些作用在 2 型糖尿病患者中降低。最初，二肽基肽酶-4 (DPP-4) 对这两种肠促胰岛素的快速降解使得基于这两种激素的可行治疗方法的开发变得复杂。然而，美国食品和药物管理局 (FDA) 已批准了 2 种基于肠促胰岛素的治疗方法，它们的作用机制增强或放大了天然 GLP-1 的作用。Exenatide 是一种首创的 GLP-1 受体激动剂，其作用机制与天然 GLP-1 相同。西他列汀抑制 DPP-4 酶，从而延长内源性 GLP-1 的半衰期。这篇综述检查了最近在 2 型糖尿病患者中进行的 GLP-1 受体激动剂和 DPP-4 抑制剂研究的数据，以及其他处于临床开发阶段的基于肠促胰岛素的治疗方法的数据。
