Department of Anatomy, Centre for Neuroendocrinology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, UK.
J Neuroendocrinol. 2021 Apr;33(4):e12960. doi: 10.1111/jne.12960.
Obesity and type 2 diabetes are key healthcare challenges of the 21st century. Subsequent to its discovery in 1948, serotonin (5-hydroxytryptamine; 5-HT) has emerged as a principal modulator of energy homeostasis and body weight, prompting it to be a target of weight loss medications (eg, fenfluramine, D-fenfluramine, fenfluramine-phentermine and sibutramine). The potential risk of off-target effects led to these medications being withdrawn from clinical use and spurred drug discovery into 5-HT receptor selective ligands. The serotonin 2C receptor (5-HT R) is the primary receptor through which 5-HT impacts feeding and body weight and 5-HT R agonist lorcaserin was released for obesity treatment in 2012. Obese patients with type 2 diabetes prescribed medications that produce weight loss commonly observe improvements in type 2 diabetes. However, recent research has provided compelling evidence that 5-HT R agonists produce effects on blood glucose and insulin sensitivity independent of weight loss. As such, neuroactive 5-HT R agonists are a potential new category of type 2 diabetes medications. 5-HT is also expressed within pancreatic β cells, is co-released with insulin and may have a role in modulating insulin secretion. This review highlights the latest advances in the function of 5-HT in body weight, insulin release and glycaemic control.
肥胖症和 2 型糖尿病是 21 世纪主要的医疗保健挑战。自 1948 年发现 5-羟色胺（5-羟色胺；5-HT）以来，它已成为能量平衡和体重的主要调节剂，促使其成为减肥药物的靶点（例如，芬氟拉明，D-芬氟拉明，芬氟拉明-苯丙醇胺和西布曲明）。非靶向效应的潜在风险导致这些药物退出临床使用，并促使人们发现了 5-HT 受体选择性配体。5-羟色胺 2C 受体（5-HT R）是 5-HT 影响摄食和体重的主要受体，5-HT R 激动剂lorcaserin 于 2012 年被用于肥胖症治疗。开处方减肥药物的 2 型糖尿病肥胖症患者通常观察到 2 型糖尿病的改善。然而，最近的研究提供了令人信服的证据，表明 5-HT R 激动剂对血糖和胰岛素敏感性的影响独立于体重减轻。因此，神经活性 5-HT R 激动剂是 2 型糖尿病药物的一个潜在新类别。5-HT 还在胰岛β细胞中表达，与胰岛素一起被释放出来，并且可能在调节胰岛素分泌中发挥作用。这篇综述强调了 5-HT 在体重、胰岛素释放和血糖控制中的最新功能进展。
