Jorsal T, Rungby J, Knop F K, Vilsbøll T
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Curr Diab Rep. 2016 Jan;16(1):1. doi: 10.1007/s11892-015-0693-3.
For decades, extensive research has aimed to clarify the role of pancreas and gut-derived peptide hormones in the regulation of glucose homeostasis and feeding behavior. Among these are the beta-cell hormone amylin and the intestinal L cell hormone glucagon-like peptide-1 (GLP-1). They exhibit distinct and yet several similar physiological actions including suppression of food intake, postprandial glucagon secretion, and gastric emptying-altogether lowering plasma glucose and body weight. These actions have been clinically exploited by the development of amylin and GLP-1 hormone analogs now used for treatment of diabetes and obesity. This review will outline the physiology and pharmacological potential of amylin and GLP-1, respectively, and focus on innovative peptide drug development leading to drugs acting on two or more distinct receptors, such as an amylin and GLP-1 peptide hybrid, potentially producing a more effective treatment strategy to combat the rapidly increasing global obesity.
几十年来，广泛的研究旨在阐明胰腺和肠道衍生的肽类激素在调节葡萄糖稳态和进食行为中的作用。其中包括β细胞激素胰淀素和肠道L细胞激素胰高血糖素样肽-1（GLP-1）。它们表现出不同但又有一些相似的生理作用，包括抑制食物摄入、餐后胰高血糖素分泌和胃排空，共同降低血糖和体重。这些作用已通过开发胰淀素和GLP-1激素类似物在临床上得到应用，这些类似物现在用于治疗糖尿病和肥胖症。本综述将分别概述胰淀素和GLP-1的生理学和药理学潜力，并重点关注创新肽药物的开发，这些药物作用于两种或更多不同的受体，如胰淀素和GLP-1肽杂交体，可能产生一种更有效的治疗策略来应对全球迅速增加的肥胖问题。
