Section of Experimental Animal Models, Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Obesity Pharmacology, Novo Nordisk A/S, Måløv, Denmark.
Basic Clin Pharmacol Toxicol. 2020 Sep;127(3):163-177. doi: 10.1111/bcpt.13427. Epub 2020 May 18.
The prevalence of obesity and associated comorbidities such as type 2 diabetes and cardiovascular disease is increasing globally. Body-weight loss reduces the risk of morbidity and mortality in obese individuals, and thus, pharmacotherapies that induce weight loss can be of great value in improving the health and well-being of people living with obesity. Treatment with amylin and calcitonin receptor agonists reduces food intake and induces weight loss in several animal models, and a number of companies have started clinical testing for peptide analogues in the treatment of obesity and/or type 2 diabetes. Studies predominantly performed in rodent models show that amylin and the dual amylin/calcitonin receptor agonist salmon calcitonin achieve their metabolic effects by engaging areas in the brain associated with regulating homeostatic energy balance. In particular, signalling via neuronal circuits in the caudal hindbrain and the hypothalamus is implicated in mediating effects on food intake and energy expenditure. We review the current literature investigating the interaction of amylin/calcitonin receptor agonists with neurocircuits that induce the observed metabolic effects. Moreover, the status of drug development of amylin and calcitonin receptor agonists for the treatment of metabolic diseases is summarized.
肥胖症及其相关并发症（如 2 型糖尿病和心血管疾病）的患病率在全球范围内不断上升。体重减轻可降低肥胖个体的发病和死亡风险，因此，可诱导体重减轻的药物治疗对于改善肥胖患者的健康和福祉具有重要价值。在几种动物模型中，胰淀素和降钙素受体激动剂可减少食物摄入并诱导体重减轻，许多公司已开始对肽类似物治疗肥胖症和/或 2 型糖尿病进行临床测试。主要在啮齿动物模型中进行的研究表明，胰淀素和双重胰淀素/降钙素受体激动剂鲑鱼降钙素通过与调节体内能量平衡相关的大脑区域发挥其代谢作用。特别是，尾部后脑和下丘脑神经元回路的信号转导与对食物摄入和能量消耗的影响有关。我们回顾了当前研究胰淀素/降钙素受体激动剂与诱导观察到的代谢作用的神经回路相互作用的文献。此外，还总结了用于治疗代谢疾病的胰淀素和降钙素受体激动剂的药物开发状况。
