Department of Diabetes, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia.
Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Am J Physiol Renal Physiol. 2020 Mar 1;318(3):F835-F842. doi: 10.1152/ajprenal.00505.2019. Epub 2020 Feb 18.
Alterations in gut homeostasis may contribute to the progression of diabetic nephropathy. There has been recent attention on the renoprotective effects of metabolite-sensing receptors in chronic renal injury, including the G protein-coupled receptor (GPR)109a, which ligates the short-chain fatty acid butyrate. However, the role of GPR109a in the development of diabetic nephropathy, a milieu of diminished microbiome-derived metabolites, has not yet been determined. The present study aimed to assess the effects of insufficient GPR109a signaling, via genetic deletion of GPR109a, on the development of renal injury in diabetic nephropathy. mice or their wild-type littermates () were rendered diabetic with streptozotocin. Mice received a control diet or an isocaloric high-fiber diet (12.5% resistant starch) for 24 wk, and gastrointestinal permeability and renal injury were determined. Diabetes was associated with increased albuminuria, glomerulosclerosis, and inflammation. In comparison, mice with diabetes did not show an altered renal phenotype. Resistant starch supplementation did not afford protection from renal injury in diabetic nephropathy. While diabetes was associated with alterations in intestinal morphology, intestinal permeability assessed in vivo using the FITC-dextran test was unaltered. GPR109a deletion did not worsen gastrointestinal permeability. Furthermore, 12.5% resistant starch supplementation, at physiological concentrations, had no effect on intestinal permeability or morphology. The results of this study indicate that GPR109a does not play a critical role in intestinal homeostasis in a model of type 1 diabetes or in the development of diabetic nephropathy.
肠道内稳态的改变可能导致糖尿病肾病的进展。最近人们关注了代谢物感应受体在慢性肾损伤中的肾保护作用，包括 G 蛋白偶联受体（GPR）109a，它可以与短链脂肪酸丁酸盐结合。然而，GPR109a 在糖尿病肾病（微生物群衍生代谢物减少的环境）发展中的作用尚未确定。本研究旨在评估通过 GPR109a 基因缺失导致 GPR109a 信号不足对糖尿病肾病中肾脏损伤发展的影响。用链脲佐菌素使 或其野生型同窝仔鼠（）糖尿病。24 周内，小鼠给予对照饮食或等热量高纤维饮食（12.5%抗性淀粉），并测定胃肠道通透性和肾脏损伤。糖尿病与白蛋白尿、肾小球硬化和炎症增加有关。相比之下，糖尿病 小鼠没有表现出改变的肾脏表型。抗性淀粉补充并不能预防糖尿病肾病中的肾脏损伤。虽然糖尿病与肠道形态改变有关，但使用 FITC-葡聚糖试验体内评估的肠道通透性未改变。GPR109a 缺失并未使胃肠道通透性恶化。此外，生理浓度的 12.5%抗性淀粉补充对肠道通透性或形态没有影响。本研究结果表明，在 1 型糖尿病模型或糖尿病肾病中，GPR109a 在肠道内稳态或糖尿病肾病的发展中不起关键作用。
