二肽基肽酶-Ⅳ抑制剂药理学作用及机制的研究进展

Progress in the pharmacological effects and mechanisms of DPP-IV inhibitors

二肽基肽酶-Ⅳ(Dipeptidyl Peptidase-IV,DPP-Ⅳ)是一个以同型二聚体形式存在于细胞膜上的多功能酶。它可以裂解包括胰高血糖素样肽-1(glucagons-like peptide 1,GLP-1)和抑胃肽(glucose-denpen-dent insulinotropic polypeptide,GIP)在内的多种肽类激素,而后两者与2型糖尿病有着密切联系。作为治疗糖尿病药物的一个新靶标,DPP-Ⅳ近年来受到极大关注。伴随着第一个DPP-Ⅳ抑制剂西他列汀(sitagliptin)在美国的上市,科研工作者对DPP-Ⅳ的研究也越来越深入。文中从DPP-Ⅳ分子的结构、分布、功能等方面进行了介绍,并对目前DPP-Ⅳ抑制剂的研发现状、临床作用及其机制的研究进展进行了综述。

Dipeptidyl peptidase-Ⅳ （DPP-Ⅳ） is a multifunctional cell surface enzyme that exists as a gloycosylated homodimer. It cleaves several peptide hormones including glucagons-like peptide 1 （GLP-1） and glucosedependent insulinotropic polypeptide （GIP）. GLP-1 and GIP closely relate to diabetes type 2. As a new target of antidiabetic agents, DPP-Ⅳ has been attracting much attention in recent years. The first DPP-Ⅳ inhibitor, sitagliptin, is coming into the market in USA, which has deeply fostered the research on DPP-Ⅳ. In this article, we introduced the structure, distribution and function of the DPP-Ⅳ molecule, and also reviewed the research progress in R＆D situation, pharmacological effects and mechanisms of DPP-Ⅳ inhibitors.