Baud Gregory, Raverdy Violeta, Bonner Caroline, Daoudi Mehdi, Caiazzo Robert, Pattou François
Univ. Lille, Inserm, U1190, Translational Research for Diabetes, F-59000, Lille, France; European Genomic Institute for Diabetes, F-59000, Lille, France; CHU Lille, Department of General and Endocrine Surgery, F-59000, Lille, France.
Univ. Lille, Inserm, U1190, Translational Research for Diabetes, F-59000, Lille, France; European Genomic Institute for Diabetes, F-59000, Lille, France.
Surg Obes Relat Dis. 2016 Jul;12(6):1206-12. doi: 10.1016/j.soard.2016.04.022. Epub 2016 Apr 26.
Active sodium-glucose transporters play a role to glucose homeostasis and represent novels targets for the management of type 2 diabetes (T2D). Sodium-glucose cotransporter 1 (SGLT1) is essential for intestinal glucose absorption from the lumen into enterocytes, whereas glucose reabsorption by the kidney is mainly mediated by sodium-glucose cotransporter 2 (SGLT2). SGLT2 inhibitors were developed to occlude SGLT2 glucose reabsorption pathway and cause glycosuria, thereby reducing plasma glucose concentrations. This new class of antidiabetic drugs has been shown to be effective in reducing cardiovascular morbidity and mortality in patients with T2D. Initial clinical studies also suggest that SGLT1 inhibition increases glucagon-like peptide 1 (GLP-1) secretion and decreases postchallenge blood glucose excursion, resulting in a dose-dependent improvement of glucose control. In parallel, we recently identified a previously unknown effect of bile diversion in gastric bypass on sodium glucose transport and postprandial glucose homeostasis, through the modulation of intestinal trafficking of endogenous sodium. This mechanism is consistent with available clinical evidence, and opens up new perspectives in metabolic surgery. More generally, the modulation of intestinal sodium-glucose cotransport appears to be a promising avenue to prevent or treat T2D.
活性钠-葡萄糖转运体对葡萄糖稳态起作用，是2型糖尿病（T2D）治疗的新靶点。钠-葡萄糖协同转运蛋白1（SGLT1）对于肠道内葡萄糖从肠腔吸收进入肠上皮细胞至关重要，而肾脏对葡萄糖的重吸收主要由钠-葡萄糖协同转运蛋白2（SGLT2）介导。SGLT2抑制剂的研发目的是阻断SGLT2介导的葡萄糖重吸收途径并导致糖尿，从而降低血浆葡萄糖浓度。这类新型抗糖尿病药物已被证明可有效降低T2D患者的心血管发病率和死亡率。初步临床研究还表明，抑制SGLT1可增加胰高血糖素样肽1（GLP-1）分泌，并减少餐后血糖波动，从而使血糖控制得到剂量依赖性改善。与此同时，我们最近发现胃旁路手术中胆汁转流对钠葡萄糖转运和餐后葡萄糖稳态有此前未知的影响，其机制是通过调节内源性钠的肠道转运实现的。这一机制与现有临床证据相符，并为代谢手术开辟了新的前景。更普遍地说，调节肠道钠-葡萄糖协同转运似乎是预防或治疗T2D的一个有前景的途径。
