Roux-en-Y gastric bypass alters intestinal glucose transport in the obese Zucker rat.
Roux-en-Y gastric bypass alters intestinal glucose transport in the obese Zucker rat.
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DOI：
10.3389/fendo.2022.901984
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发表时间：
2022
影响因子：
5.2
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中科院分区：
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胃肠道在调节葡萄糖稳态和肠道内分泌功能中起主要作用。本研究探讨Roux-en-Y胃旁路术（RYGB）对肥胖Zucker大鼠（ZR）肠道GLP-1、葡萄糖转运蛋白表达和功能的影响。研究了两组ZR：RYGB和假手术配对喂养（PF）喂养的大鼠。每天测量体重和摄食量。在术后第21天（POD），进行口服葡萄糖试验（OGT），测量基础和30分钟血浆、门静脉葡萄糖和胰高血糖素样肽-1（GLP-1）水平。在单独的ZR中，在POD 21收获胆胰、Roux肢（Roux）和共同通道（CC）肠段。RYGB组体重下降。RYGB后基础和30分钟OGT血浆和门静脉葡萄糖水平降低。基础血浆GLP-1水平相似，而在RYGB后30分钟内观察到GLP-1水平增加4.5倍（与PF相比）。RYGB后基础和30分钟门静脉GLP-1水平的增加伴随着Roux和CC段中胰高血糖素原和PC 1/3、GPR 119蛋白的mRNA表达增加。FFAR 2/3在Roux段的mRNA和蛋白水平均升高。RYGB降低Roux和CC节段刷状缘葡萄糖转运、转运蛋白（SGLT 1和GLUT 2）和Tas 1 R1/Tas 1 R3和α-gustducin的mRNA水平。在ZR模型中，肠道葡萄糖转运的减少和餐后GLP-1释放的增强与RYGB后GRP 119和FFAR 2/3的增加相关。RYGB后肠道葡萄糖转运调节和L细胞受体调节GLP-1分泌的减少代表了改善血糖控制的潜在机制。
The gastrointestinal tract plays a major role in regulating glucose homeostasis and gut endocrine function. The current study examines the effects of Roux-en-Y gastric bypass (RYGB) on intestinal GLP-1, glucose transporter expression and function in the obese Zucker rat (ZR). Two groups of ZRs were studied: RYGB and sham surgery pair-fed (PF) fed rats. Body weight and food intake were measured daily. On post-operative day (POD) 21, an oral glucose test (OGT) was performed, basal and 30-minute plasma, portal venous glucose and glucagon-like peptide-1 (GLP-1) levels were measured. In separate ZRs, the biliopancreatic, Roux limb (Roux) and common channel (CC) intestinal segments were harvested on POD 21. Body weight was decreased in the RYGB group. Basal and 30-minute OGT plasma and portal glucose levels were decreased after RYGB. Basal plasma GLP-1 levels were similar, while a 4.5-fold increase in GLP-1 level was observed in 30-minute after RYGB (vs. PF). The increase in basal and 30-minute portal venous GLP-1 levels after RYGB were accompanied by increased mRNA expressions of proglucagon and PC 1/3, GPR119 protein in the Roux and CC segments. mRNA and protein levels of FFAR2/3 were increased in Roux segment. RYGB decreased brush border glucose transport, transporter proteins (SGLT1 and GLUT2) and mRNA levels of Tas1R1/Tas1R3 and α-gustducin in the Roux and CC segments. Reductions in intestinal glucose transport and enhanced post-prandial GLP-1 release were associated with increases in GRP119 and FFAR2/3 after RYGB in the ZR model. Post-RYGB reductions in the regulation of intestinal glucose transport and L cell receptors regulating GLP-1 secretion represent potential mechanisms for improved glycemic control.