Gastric Bypass and Sleeve Gastrectomy induce a new gastric mucosa phenotype with increased number of Glucagon-Like Peptide-1 expressing cells

The Glucagon-Like Peptide-1 (GLP-1) is a proglucagon-derived peptide with regulatory effects on many tissues, including the pancreas, stomach, liver, brain and heart. The rapid inactivation of intestinally secreted GLP-1 by DPP-4 enzyme raises the question of its production in proximity of its targets. Here we show some epithelial cells producing GLP-1 in the stomach of rats and humans. These cells respond specifically to intragastric load of glucose by increasing GLP-1 levels in the portal vein, in vivo in the rat. GLP-1 is known as an incretin, it decreases blood glucose levels after a meal by increasing insulin secretion in response to glucose. The increased GLP-1 secretion in obese individuals who have undergone bariatric surgery is considered as a keystone in the glycemic improvement observed in those patients. Here we show that obese rats that underwent RYGB or VSG exhibit a new gastric mucosa phenotype with expansion and hyperplasia of the mucus neck cells, and increased density of gastric GLP-1 expressing cells compared to sham animals. These findings highlight a potential role of stomach-derived GLP-1 in the outcomes of bariatric surgeries and raise the question of its role in physiology and metabolism.

胰高血糖素样肽-1（Glucagon-Like Peptide-1, GLP-1）是一种源自胰高血糖素原的肽类物质，对胰腺、胃、肝脏、大脑与心脏等多种组织具有调节作用。肠道分泌的GLP-1会被二肽基肽酶4（Dipeptidyl Peptidase-4, DPP-4）快速灭活，这一现象引出了关键科学问题：GLP-1是否会在其作用靶点附近产生？本研究证实，大鼠与人类的胃组织中存在可合成GLP-1的上皮细胞。在大鼠体内实验中，这类细胞可通过升高门静脉内的GLP-1水平，特异性响应胃内葡萄糖负荷。已知GLP-1属于肠促胰岛素（incretin），可通过促进葡萄糖诱导的胰岛素分泌，降低餐后血糖水平。接受减重代谢手术的肥胖个体，其GLP-1分泌水平升高被认为是这类患者术后血糖改善的核心机制。本研究还发现，接受Roux-en-Y胃旁路术（Roux-en-Y Gastric Bypass, RYGB）或袖状胃切除术（Vertical Sleeve Gastrectomy, VSG）的肥胖大鼠，其胃黏膜呈现出新的表型：黏液颈细胞扩张与增生，且胃内GLP-1阳性细胞的密度较假手术组动物显著升高。上述研究结果凸显了胃源性GLP-1在减重代谢手术疗效中的潜在作用，同时也为探究其在生理与代谢过程中的功能提出了新的科学问题。