School of Biological Sciences, Maurice Wilkins Centre for Molecular Biodiscovery and Centre for Brain Research, University of Auckland, Auckland, New Zealand (D.L.H.); Amylin Pharmaceuticals LLC, San Diego, California (S.C., D.G.P.); Institute of Veterinary Physiology, Institute of Laboratory Animal Sciences and Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland (T.A.L.); and Intercept Pharmaceuticals, Inc., San Diego, California (J.D.R.)
School of Biological Sciences, Maurice Wilkins Centre for Molecular Biodiscovery and Centre for Brain Research, University of Auckland, Auckland, New Zealand (D.L.H.); Amylin Pharmaceuticals LLC, San Diego, California (S.C., D.G.P.); Institute of Veterinary Physiology, Institute of Laboratory Animal Sciences and Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland (T.A.L.); and Intercept Pharmaceuticals, Inc., San Diego, California (J.D.R.).
Pharmacol Rev. 2015 Jul;67(3):564-600. doi: 10.1124/pr.115.010629.
Amylin is a pancreatic β-cell hormone that produces effects in several different organ systems. Here, we review the literature in rodents and in humans on amylin research since its discovery as a hormone about 25 years ago. Amylin is a 37-amino-acid peptide that activates its specific receptors, which are multisubunit G protein-coupled receptors resulting from the coexpression of a core receptor protein with receptor activity-modifying proteins, resulting in multiple receptor subtypes. Amylin's major role is as a glucoregulatory hormone, and it is an important regulator of energy metabolism in health and disease. Other amylin actions have also been reported, such as on the cardiovascular system or on bone. Amylin acts principally in the circumventricular organs of the central nervous system and functionally interacts with other metabolically active hormones such as cholecystokinin, leptin, and estradiol. The amylin-based peptide, pramlintide, is used clinically to treat type 1 and type 2 diabetes. Clinical studies in obesity have shown that amylin agonists could also be useful for weight loss, especially in combination with other agents.
胰岛淀粉样多肽是一种胰腺β细胞激素,在多个不同的器官系统中发挥作用。本文回顾了约 25 年前发现其作为激素以来,在啮齿动物和人类中关于胰岛淀粉样多肽研究的文献。胰岛淀粉样多肽是一种由 37 个氨基酸组成的肽,能激活其特定的受体,这些受体是由核心受体蛋白与受体活性修饰蛋白共同表达产生的多亚基 G 蛋白偶联受体,从而形成多种受体亚型。胰岛淀粉样多肽的主要作用是作为血糖调节激素,在健康和疾病中是能量代谢的重要调节剂。其他胰岛淀粉样多肽的作用也有报道,如对心血管系统或骨骼的作用。胰岛淀粉样多肽主要在中枢神经系统的室周器官中发挥作用,并与其他代谢活性激素如胆囊收缩素、瘦素和雌二醇相互作用。基于胰岛淀粉样多肽的肽类药物普兰林肽被临床用于治疗 1 型和 2 型糖尿病。肥胖症的临床研究表明,胰岛淀粉样多肽激动剂也可能对减肥有用,尤其是与其他药物联合使用时。