Department of Microbiology, Kanak Manjari Institute of Pharmaceutical Sciences, Rourkela, Orissa, India.
Indian J Pharmacol. 2008 Jan;40(1):10-4. doi: 10.4103/0253-7613.40482.
Proper control of blood sugar in type 2 diabetes mellitus (T2DM) is not adequate till now in spite of use of well-planned dosage regimens containing oral hypoglycemic agents/insulin or both. Recently, the role of 'incretins,' particularly that of glucagon-like peptide-1 (GLP-1) in glucose homeostasis has been firmly established. The peptide (GLP-1) increases insulin secretion while decreasing that of glucagon in response to rise in plasma glucose in addition to delay of gastric emptying time, reduction of appetite, preservation of beta-cell function, and increase in beta-cell mass all of which will contribute toward lowering of blood sugar in T2DM. But the peptide hormone cannot be used orally as such because of its very short plasma half-life (2 min) and chemical nature, which needs continuous i.v. infusion or repeated s.c. or i.v. injections at short intervals. Hence, to prolong the duration of action of endogenous GLP-1, compounds have been synthesized which inhibit the enzyme dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for metabolic degradation of GLP-1. One such compound is vildagliptin. In this article, an attempt has been made to compile some of the established recent advances in the therapeutic utility of vildagliptin along with a discussion about the physiological role of endogenous GLP-1 and its metabolism by DPP-4.
尽管使用了包含口服降糖药/胰岛素或两者的精心计划的剂量方案,但 2 型糖尿病(T2DM)的血糖控制仍然不充分。最近,“肠促胰岛素”,特别是胰高血糖素样肽-1(GLP-1)在血糖稳态中的作用已得到充分证实。该肽(GLP-1)在血糖升高时增加胰岛素分泌,同时减少胰高血糖素分泌,此外还可延迟胃排空时间、减少食欲、保护β细胞功能以及增加β细胞质量,所有这些都有助于降低 T2DM 的血糖。但是,由于其血浆半衰期(2 分钟)和化学性质很短,该肽激素不能口服使用,需要连续静脉输注或短时间内重复皮下或静脉注射。因此,为了延长内源性 GLP-1 的作用持续时间,已经合成了抑制二肽基肽酶-4(DPP-4)的化合物,DPP-4 是负责 GLP-1 代谢降解的酶。其中一种化合物是维达列汀。本文试图编译一些关于维达列汀治疗用途的最新进展,并讨论内源性 GLP-1 的生理作用及其被 DPP-4 代谢的情况。