Amylin Pharmaceuticals, Inc. San Diego, CA, USA.
Br J Pharmacol. 2012 May;166(1):121-36. doi: 10.1111/j.1476-5381.2011.01537.x.
The discoveries of the incretin hormone glucagon-like peptide-1 (GLP-1) and the β-cell hormone amylin have translated into hormone-based therapies for diabetes. Both classes of molecules also exhibit weight-lowering effects and have been investigated for their anti-obesity potential. In the present review, we explore the mechanisms underlying the physiological and pharmacological actions of GLP-1 and amylin agonism. Despite their similarities (e.g. both molecular classes slow gastric emptying, decrease glucagon and inhibit food intake), there are important distinctions between the central and/or peripheral pathways that mediate their effects on glycaemia and energy balance. We suggest that understanding the similarities and differences between these molecules holds important implications for the development of novel, combination-based therapies, which are increasingly the norm for diabetes/metabolic disease. Finally, the future of GLP-1- and amylin agonist-based therapeutics is discussed.
肠促胰岛素激素胰高血糖素样肽-1（GLP-1）和胰岛β细胞激素胰淀素的发现已转化为基于激素的糖尿病治疗方法。这两类分子也具有降低体重的作用，并已针对其抗肥胖潜力进行了研究。在本综述中，我们探讨了 GLP-1 和胰淀素激动剂的生理和药理学作用的机制。尽管它们具有相似性（例如，这两类分子均能减缓胃排空，降低胰高血糖素并抑制食物摄入），但介导它们对血糖和能量平衡的影响的中枢和/或外周途径存在重要差异。我们认为，了解这些分子之间的异同对于开发新的基于联合治疗的方法具有重要意义，而这对于糖尿病/代谢疾病来说已经越来越成为常态。最后，讨论了基于 GLP-1 和胰淀素激动剂的治疗方法的未来。
