Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
J Mol Endocrinol. 2024 Feb 22;72(4). doi: 10.1530/JME-23-0112. Print 2024 May 1.
Enteroendocrine cells located along the gastrointestinal epithelium sense different nutrients/luminal contents that trigger the secretion of a variety of gut hormones with different roles in glucose homeostasis and appetite regulation. The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are involved in the regulation of insulin secretion, appetite, food intake and body weight after their nutrient-induced secretion from the gut. GLP-1 mimetics have been developed and used in the treatment of type 2 diabetes mellitus and obesity. Modulating the release of endogenous intestinal hormones may be a promising approach for the treatment of obesity and type 2 diabetes without surgery. For that reason, current understanding of the cellular mechanisms underlying intestinal hormone secretion will be the focus of this review. The mechanisms controlling hormone secretion depend on the nature of the stimulus, involving a variety of signalling pathways including ion channels, nutrient transporters and G-protein-coupled receptors.
沿胃肠道上皮分布的肠内分泌细胞能够感知不同的营养物质/腔内容物,这些物质会触发各种胃肠激素的分泌,这些激素在葡萄糖稳态和食欲调节中发挥不同的作用。肠促胰岛素激素胰高血糖素样肽-1(GLP-1)和葡萄糖依赖性胰岛素释放肽(GIP)参与了胰岛素分泌、食欲、食物摄入和体重的调节,这些激素在受到营养物质刺激后从肠道中分泌。GLP-1 类似物已被开发并用于 2 型糖尿病和肥胖症的治疗。调节内源性肠激素的释放可能是一种无需手术即可治疗肥胖症和 2 型糖尿病的有前途的方法。出于这个原因,目前对肠道激素分泌的细胞机制的理解将是本次综述的重点。控制激素分泌的机制取决于刺激的性质,涉及多种信号通路,包括离子通道、营养物质转运体和 G 蛋白偶联受体。