摘要
在过去的几十年中,环境和生活方式的改变使得2型糖尿病患者的数量急剧增加, 其中一个重要的病理基础是胰岛素分泌缺陷。胰高血糖素样肽1(GLP-1)是一种由肠道细胞产生及分泌的多肽激素, 该激素以葡萄糖浓度依赖性方式促进胰岛β细胞分泌胰岛素, 调节血糖水平。研究表明GLP-1是糖尿病治疗中的一个有效靶点, 药物研发目前主要集中于GLP-1受体激动剂和降解酶抑制剂两个方面。以其强大的生物学活性为基础, GLP-1药物在临床上表现出高效、低副作用的显著优势。在此, 我们对GLP-1生物学和基于GLP-1的抗糖尿病药物研发进行综述。
Environmental and lifestyle factors together account for the dramatic increase of type 2 diabetes in the past decades, in which defective insulin secretion emerges as the major culprit. Glucagon-like peptide l （GLP-1） is a peptide secreted from the intestine in response to nutrient ingestion, and plays an essential role in the regulation of blood glucose level by stimulating glucoses-dependent insulin secretion. Recently, GLP-1 develops to be a viable therapeutic target for the treatment of type 2 diabetes, by means of GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Stemmed fi^om its potent physiological activities, GLP-1-based therapies are clinically efficient and safe for both early and late stages of the disease, with low risk of adverse events. In this review, a comprehensive understanding of GLP-1 biology and the recent development of GLP-1-based antidiabetic therapy are summarized.
基金
The National Key Basic Research Program of China(Grant No. 2011CBA01100)
