Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Obes Surg. 2018 Dec;28(12):3851-3861. doi: 10.1007/s11695-018-3351-4.
The unique effects of gastric resection after vertical sleeve gastrectomy (VSG) on type 2 diabetes mellitus remain unclear. This work aimed to investigate the effects of VSG on gastric leptin expression and intestinal glucose absorption in high-fat diet-induced obesity.
Male C57BL/6J mice were fed a high-fat diet (HFD) to induce obesity. HFD mice were randomized into VSG and sham-operation groups, and the relevant parameters were measured at 8 weeks postoperation.
Higher gastric leptin expression and increased intestinal glucose transport were observed in the HFD mice. Furthermore, VSG reduced gastric leptin expression and the intestinal absorption of alimentary glucose. Both exogenous leptin replenishment during the oral glucose tolerance test (OGTT) and the addition of leptin into the everted isolated jejunum loops in vitro restored the glucose transport capacity in VSG-operated mice, and this effect was abolished when the glucose transporter GLUT2 was blocked with phloretin. Moreover, phloretin almost completely suppressed glucose transport in the HFD mice. Intestinal immunohistochemistry in the obese mice showed increased GLUT2 and diminished sodium glucose co-transporter 1 (SGLT-1) in the apical membrane of enterocytes. Decreased GLUT2 and enhanced SGLT1 were observed following VSG. VSG also reduced the phosphorylation status of protein kinase C isoenzyme β II (PKCβ II) in the jejunum, which was stimulated by the combination of leptin and glucose.
Our data demonstrated that the decreased secretion of gastric leptin in VSG results in a decrease in intestinal glucose absorption via modulation of GLUT2 translocation.
垂直袖状胃切除术（VSG）后胃切除术对 2 型糖尿病的独特影响尚不清楚。本研究旨在探讨 VSG 对高脂饮食诱导肥胖的胃瘦素表达和肠道葡萄糖吸收的影响。
雄性 C57BL/6J 小鼠喂食高脂肪饮食（HFD）以诱导肥胖。HFD 小鼠随机分为 VSG 和假手术组，术后 8 周测量相关参数。
HFD 小鼠胃瘦素表达升高，肠道葡萄糖转运增加。此外，VSG 降低了胃瘦素表达和肠道对食物葡萄糖的吸收。口服葡萄糖耐量试验（OGTT）期间外源性补充瘦素和体外将瘦素加入外翻分离空肠环均可恢复 VSG 手术小鼠的葡萄糖转运能力，而用 phloretin 阻断葡萄糖转运体 GLUT2 则消除了这种作用。此外，phloretin 几乎完全抑制了 HFD 小鼠的葡萄糖转运。肥胖小鼠的肠道免疫组织化学显示，肠上皮细胞顶膜的 GLUT2 增加，钠葡萄糖共转运蛋白 1（SGLT-1）减少。VSG 后观察到 GLUT2 减少和 SGLT1 增强。VSG 还降低了瘦素和葡萄糖联合刺激的空肠蛋白激酶 C 同工酶β II（PKCβ II）的磷酸化状态。
我们的数据表明，VSG 中胃瘦素分泌减少通过调节 GLUT2 易位导致肠道葡萄糖吸收减少。
