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胰高血糖素样肽-1受体激动剂在糖尿病管理中的作用与发展

Role and development of GLP-1 receptor agonists in the management of diabetes.

作者信息

Chia Chee W, Egan Josephine M

机构信息

National Institutes of Health, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA.

出版信息

Diabetes Metab Syndr Obes. 2009 May 15;2:37.

Abstract

Glucagon-like peptide-1 (GLP-1) is a hormone secreted from enteroendocrine L cells of the intestine in response to food. Exogenous GLP-1 administration at pharmacological doses results in many effects that are beneficial for treating type 2 diabetes, these include: (1) an increase in insulin secretion from beta cells; (2) a suppression of glucagon secretion from alpha cells in the presence of hyperglycemia but not hypoglycemia; (3) a delay in gastric emptying and gut motility which in turns delays absorption of ingested nutrients and dampens post-prandial glucose excursion; and (4) an increase in the duration of postprandial satiety therefore suppressing appetite and decreasing food intake which eventually leads to weight loss. However, GLP-1 is subject to rapid enzymatic degradation, and therefore, not suitable for long-term treatment. A synthetic enzyme-resistant GLP-1 receptor agonist that reproduces the biological effects of GLP-1 is in use and more are under development. This review aims at providing a summary of the properties of GLP-1 and the development of GLP-1-based therapies for treatment of diabetes.

摘要

胰高血糖素样肽-1(GLP-1)是一种由肠道内分泌L细胞在进食后分泌的激素。给予药理剂量的外源性GLP-1会产生许多对治疗2型糖尿病有益的作用,这些作用包括:(1)β细胞胰岛素分泌增加;(2)在高血糖而非低血糖情况下,α细胞胰高血糖素分泌受到抑制;(3)胃排空和肠道蠕动延迟,进而延缓摄入营养物质的吸收并减轻餐后血糖波动;(4)餐后饱腹感持续时间增加,从而抑制食欲并减少食物摄入量,最终导致体重减轻。然而,GLP-1会迅速被酶降解,因此不适合长期治疗。一种能重现GLP-1生物学效应的合成酶抗性GLP-1受体激动剂正在使用,并且还有更多处于研发阶段。本综述旨在总结GLP-1的特性以及基于GLP-1的糖尿病治疗方法的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/759c/3048014/b800517c4006/dmso-2-037f1.jpg

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