Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Nat Rev Endocrinol. 2019 Apr;15(4):226-237. doi: 10.1038/s41574-019-0168-8.
Gut hormones have many key roles in the control of metabolism, as they target diverse tissues involved in the control of intestinal function, insulin secretion, nutrient assimilation and food intake. Produced by scattered cells found along the length of the intestinal epithelium, gut hormones generate signals related to the rate of nutrient absorption, the composition of the luminal milieu and the integrity of the epithelial barrier. Gut hormones already form the basis for existing and developing therapeutics for type 2 diabetes mellitus and obesity, exemplified by the licensed glucagon-like peptide 1 (GLP1) mimetics and dipeptidyl peptidase inhibitors that enhance GLP1 receptor activation. Modulating the release of the endogenous stores of GLP1 and other gut hormones is thought to be a promising strategy to mimic bariatric surgery with its multifaceted beneficial effects on food intake, body weight and blood glucose levels. This Review focuses on the molecular mechanisms underlying the modulation of gut hormone release by food ingestion, obesity and the gut microbiota. Depending on the nature of the stimulus, release of gut hormones involves recruitment of a variety of signalling pathways, including G protein-coupled receptors, nutrient transporters and ion channels, which are targets for future therapeutics for diabetes mellitus and obesity.
肠激素在代谢控制中具有许多关键作用，因为它们针对参与肠道功能、胰岛素分泌、营养吸收和食物摄入控制的多种组织发挥作用。肠激素由沿着肠上皮长度分布的散在细胞产生，产生与营养吸收速度、腔环境组成和上皮屏障完整性相关的信号。肠激素已经成为治疗 2 型糖尿病和肥胖症的现有和正在开发的治疗方法的基础，例如已获得许可的胰高血糖素样肽 1 (GLP1) 类似物和二肽基肽酶抑制剂，它们增强 GLP1 受体的激活。调节内源性 GLP1 和其他肠激素的释放被认为是一种很有前途的策略，可以模拟减肥手术对食物摄入、体重和血糖水平的多方面有益影响。本综述重点介绍了食物摄入、肥胖和肠道微生物群调节肠激素释放的分子机制。根据刺激的性质，肠激素的释放涉及多种信号通路的招募，包括 G 蛋白偶联受体、营养转运体和离子通道，它们是治疗糖尿病和肥胖症的未来治疗方法的靶点。
