期刊
JOURNAL OF NEUROENDOCRINOLOGY
卷 33, 期 4, 页码 -出版社
WILEY
DOI: 10.1111/jne.12960
关键词
5‐ HT; body weight; glycaemic control; insulin; obesity; serotonin
资金
- BBSRC [BB/R01857X/1] Funding Source: UKRI
This paper discusses the role of serotonin in energy balance and weight regulation, as well as the potential effects of 5-HT2CR agonists in combating obesity and type 2 diabetes.
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 The potential risk of off-target effects led to these medications being withdrawn from clinical use and spurred drug discovery into 5-HT receptor selective ligands.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-HT2CR) is the primary receptor through which 5-HT impacts feeding and body weight and 5-HT2CR 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-HT2CR agonists produce effects on blood glucose and insulin sensitivity independent of weight loss. As such, neuroactive 5-HT2CR agonists are a potential new category of type 2 diabetes medications. 5-HT is also expressed within pancreatic beta 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.
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