Jurowich Christian Ferdinand, Otto Christoph, Rikkala Prashanth Reddy, Wagner Nicole, Vrhovac Ivana, Sabolić Ivan, Germer Christoph-Thomas, Koepsell Hermann
Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Straße 6, 97080 Würzburg, Germany.
Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstraße 6, 97070 Würzburg, Germany.
J Diabetes Res. 2015;2015:490365. doi: 10.1155/2015/490365. Epub 2015 Jun 22.
Bariatric operations in obese patients with type 2 diabetes often improve diabetes before weight loss is observed. In patients mainly Roux-en-Y-gastric bypass with partial stomach resection is performed. Duodenojejunal bypass (DJB) and ileal interposition (IIP) are employed in animal experiments. Due to increased glucose exposition of L-cells located in distal ileum, all bariatric surgery procedures lead to higher secretion of antidiabetic glucagon like peptide-1 (GLP-1) after glucose gavage. After DJB also downregulation of Na(+)-d-glucose cotransporter SGLT1 was observed. This suggested a direct contribution of decreased glucose absorption to the antidiabetic effect of bariatric surgery. To investigate whether glucose absorption is also decreased after IIP, we induced diabetes with decreased glucose tolerance and insulin sensitivity in male rats and investigated effects of IIP on diabetes and SGLT1. After IIP, we observed weight-independent improvement of glucose tolerance, increased insulin sensitivity, and increased plasma GLP-1 after glucose gavage. The interposed ileum was increased in diameter and showed increased length of villi, hyperplasia of the epithelial layer, and increased number of L-cells. The amount of SGLT1-mediated glucose uptake in interposed ileum was increased 2-fold reaching the same level as in jejunum. Thus, improvement of glycemic control by bariatric surgery does not require decreased glucose absorption.
肥胖的2型糖尿病患者接受减肥手术后,往往在体重减轻之前糖尿病病情就有所改善。对于这类患者,主要实施的是带有部分胃切除的Roux-en-Y胃旁路手术。十二指肠空肠旁路术(DJB)和回肠置管术(IIP)则用于动物实验。由于位于回肠末端的L细胞对葡萄糖的暴露增加,所有减肥手术操作都会导致在给予葡萄糖后抗糖尿病的胰高血糖素样肽-1(GLP-1)分泌增加。在DJB术后,还观察到钠-葡萄糖协同转运蛋白1(SGLT1)下调。这表明葡萄糖吸收减少对减肥手术的抗糖尿病作用有直接贡献。为了研究IIP术后葡萄糖吸收是否也会减少,我们在雄性大鼠中诱导出葡萄糖耐量降低和胰岛素敏感性降低的糖尿病模型,并研究IIP对糖尿病和SGLT1的影响。IIP术后,我们观察到葡萄糖耐量有与体重无关的改善、胰岛素敏感性增加以及给予葡萄糖后血浆GLP-1增加。置入的回肠直径增大,绒毛长度增加,上皮层增生,L细胞数量增多。置入回肠中SGLT1介导的葡萄糖摄取量增加了2倍,达到与空肠相同的水平。因此,减肥手术改善血糖控制并不需要减少葡萄糖吸收。