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| 在过去的30年中，全球和我国的2型糖尿病（T2DM）患病率急剧上升，给社会带来了日益沉重的负担。总体来
说，目前T2DM的控制达标率较低，且在过去5年中未能进一步提高。目前临床上使用的降糖药物，在保护胰岛β细胞功能方面也尚无突破性进展。因此寻找新的
治疗机制和研发新药物是提高T2DM治疗达标率的希望之一，而胰高血糖素样肽-1（GLP-1）类似物的问世，是这方面的一个成功典范。 GLP—1是一种由胃肠内分泌细胞产生的肽类物质，属于肠促胰素的一种。它能够通过促进胰岛素分泌、刺激胰岛β细胞增生、阻止胰岛β细胞凋亡、抑制胰高血糖素的释放、抑制胃肠道蠕动和胃液分泌、延迟胃排空、产生饱胀感和食欲下降等多重途径来控制血糖。 无疑，GLP—1将会开启未来糖尿病治疗的新篇章！ 为了增加大众对于GLP-1相关最新资讯的了解，国际知名继续医学教育网站Medscape 及Peerview 开辟了“GLP-1资讯专栏”，收集整理最新的GLP-1研究进展、糖尿病相关诊治最新资讯，希望给予关注糖尿病及GLP-1进展的你最新最全的资讯！ Medscape—— “GLP-1等肠促胰素资讯中心” http://www.medscape.com/resource/incretinhormone （ 此网站需要注册，可使用自己的帐号，或是使用公用帐号和密码：均为GLPglp1 ） 医学岛推荐原文： Glucagon-like peptide-1 GLP-1 is a naturally occurring 30-amino acid eptide synthesised in intestinal endocrine L cells. GLP-1 mediates glucose homeostasis through stimulation of glucose-dependent insulin secretion, biosynthesis of insulin and inhibition of glucagon secretion. These effects have potential clinical value in type 2 diabetes. However, because native GLP-1 is rapidly degraded to its inactive form by dipeptidyl peptidase-4 (DPP-4), it has a short half-life in vivo. Strategies to overcome this therapeutic limitation include developing GLP-1 mimetics and analogues with longer half-lives and to inhibit DPP-4. Exenatide (exendin-4) is a 39-amino acid peptide originally derived from the venom of the Gila monster lizard, and shares a 53% sequence identity with human GLP-1. Exenatide has a longer circulating half-life, reflecting relative resistance to DPP-4 degradation, and is administered twice daily. Liraglutide is a once-daily human GLP-1 analogue with high (97%) sequence identity. The specific structural modifications that characterise liraglutide result in increased self-association (allowing slow absorption from the subcutaneous depot), promote albumin binding and reduce susceptibility to DPP-4, giving liraglutide a halflife of 13 hours after once-daily administration. Preliminary studies of exenatide and liraglutide showclinically relevant reductions in glycosylated haemoglobin A1c (HbA1c) compared with placebo,without hypoglycaemia andwithweight loss of up to 3 kg. DPP-4 inhibitors, such as vildagliptin (not available in the USA) and sitagliptin can help stabilise postprandial GLP-1 levels and thus produce desirable effects on insulin and glucagon production. The potential forweight reductionwith DPP-4 inhibitors appears limited, perhaps reflecting the limited increase in GLP-1 levels achieved with these agents. |
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