Mathiesen David S, Lund Asger, Vilsbøll Tina, Knop Filip K, Bagger Jonatan I
Center for Clinical Metabolic Research, Gentofte Hospital, Hellerup, Denmark.
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
Front Endocrinol (Lausanne). 2021 Jan 8;11:617400. doi: 10.3389/fendo.2020.617400. eCollection 2020.
The hormones amylin and calcitonin interact with receptors within the same family to exert their effects on the human organism. Calcitonin, derived from thyroid C cells, is known for its inhibitory effect on osteoclasts. Calcitonin of mammalian origin promotes insulin sensitivity, while the more potent calcitonin extracted from salmon additionally inhibits gastric emptying, promotes gallbladder relaxation, increases energy expenditure and induces satiety as well as weight loss. Amylin, derived from pancreatic beta cells, regulates plasma glucose by delaying gastric emptying after meal ingestion, and modulates glucagon secretion and central satiety signals in the brain. Thus, both hormones seem to have metabolic effects of relevance in the context of non-alcoholic fatty liver disease (NAFLD) and other metabolic diseases. In rats, studies with dual amylin and calcitonin receptor agonists have demonstrated robust body weight loss, improved glucose tolerance and a decreased deposition of fat in liver tissue beyond what is observed after a body weight loss. The translational aspects of these preclinical data currently remain unknown. Here, we describe the physiology, pathophysiology, and pharmacological effects of amylin and calcitonin and review preclinical and clinical findings alluding to the future potential of amylin and calcitonin-based drugs for the treatment of obesity and NAFLD.
激素胰淀素和降钙素与同一家族中的受体相互作用，从而对人体发挥作用。降钙素由甲状腺C细胞产生，以其对破骨细胞的抑制作用而闻名。哺乳动物来源的降钙素可促进胰岛素敏感性，而从鲑鱼中提取的活性更强的降钙素还可抑制胃排空、促进胆囊舒张、增加能量消耗并诱导饱腹感以及体重减轻。胰淀素由胰腺β细胞产生，通过在进食后延迟胃排空来调节血糖，并调节胰高血糖素分泌和大脑中的中枢饱腹感信号。因此，这两种激素在非酒精性脂肪性肝病（NAFLD）和其他代谢性疾病的背景下似乎都具有相关的代谢作用。在大鼠中，对双重胰淀素和降钙素受体激动剂的研究表明，体重显著减轻、葡萄糖耐量改善，并且肝脏组织中的脂肪沉积减少，减重后观察到的效果更为明显。目前这些临床前数据的转化情况尚不清楚。在此，我们描述了胰淀素和降钙素的生理学、病理生理学及药理作用，并回顾了临床前和临床研究结果，这些结果暗示了基于胰淀素和降钙素的药物在治疗肥胖症和NAFLD方面的未来潜力。
