Université de Paris, Inserm U1149, Centre de Recherche sur l'inflammation, Paris, France.
Service de Chirurgie Générale Œsogastrique et Bariatrique, Hôpital Bichat - Claude-Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France.
Nat Commun. 2021 Jan 4;12(1):110. doi: 10.1038/s41467-020-20301-1.
Glucagon-Like Peptide-1 (GLP-1) undergoes rapid inactivation by dipeptidyl peptidase-4 (DPP4) suggesting that target receptors may be activated by locally produced GLP-1. Here we describe GLP-1 positive cells in the rat and human stomach and found these cells co-expressing ghrelin or somatostatin and able to secrete active GLP-1 in the rats. In lean rats, a gastric load of glucose induces a rapid and parallel rise in GLP-1 levels in both the gastric and the portal veins. This rise in portal GLP-1 levels was abrogated in HFD obese rats but restored after vertical sleeve gastrectomy (VSG) surgery. Finally, obese rats and individuals operated on Roux-en-Y gastric bypass and SG display a new gastric mucosa phenotype with hyperplasia of the mucus neck cells concomitant with increased density of GLP-1 positive cells. This report brings to light the contribution of gastric GLP-1 expressing cells that undergo plasticity changes after bariatric surgeries, to circulating GLP-1 levels.
胰高血糖素样肽-1(GLP-1)可被二肽基肽酶-4(DPP4)迅速失活,这表明靶受体可能被局部产生的 GLP-1 激活。在这里,我们描述了大鼠和人胃中的 GLP-1 阳性细胞,并发现这些细胞共表达胃饥饿素或生长抑素,并能够在大鼠中分泌有活性的 GLP-1。在瘦大鼠中,胃负荷葡萄糖可迅速且平行地增加胃和门静脉中 GLP-1 的水平。在高脂肪饮食肥胖大鼠中,这种门静脉 GLP-1 水平的升高被阻断,但在垂直袖状胃切除术(VSG)手术后得到恢复。最后,肥胖大鼠和接受 Roux-en-Y 胃旁路和 SG 手术的个体表现出一种新的胃黏膜表型,黏液颈细胞增生,同时 GLP-1 阳性细胞密度增加。本报告揭示了肥胖症患者胃 GLP-1 表达细胞在减重手术后发生可塑性变化,从而影响循环 GLP-1 水平。