Domon Ayaka, Katayama Kentaro, Yamada Takashi, Tochigi Yuki, Suzuki Hiroetsu
Laboratory of Veterinary Physiology, Faculty of Veterinary Science, School of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonancho, Musashino-shi, Tokyo 180-8602, Japan.
Biology (Basel). 2021 Jul 8;10(7):633. doi: 10.3390/biology10070633.
The kidneys participate in the regulation of systemic glucose metabolism via gluconeogenesis, insulin degradation, and the tubular reabsorption of glucose. The present study characterized rats from a strain of a novel type 2 diabetes model with enlarged kidneys (DEK). Histological and biochemical analyses of DEK rats were performed to assess the relationships between their kidneys and hyperglycemia. The kidney weight of diabetic DEK (DEK-DM) gradually increased over time from the onset of diabetes, with the glomerular number being higher in DEK-DM than in normal DEK (DEK-cont). A positive correlation between blood glucose level and kidney weight was observed in DEK-DM. The similar glomerular size and single glomerular creatinine clearance in DEK-cont and DEK-DM indicated that glomerular hypertrophy and hyperfiltration were not involved in the renal enlargement. Uninephrectomy (1/2Nx) in DEK-DM resulted in a reduction in blood glucose level at 7-28 post-operation days, with this concentration remaining lower than in Sham group until 84 days post-operation. 1/2Nx also improved systemic conditions, including reduced body weight gain, polyuria, polydipsia, and hyperphagia. Plasma concentrations of Na, total cholesterol, albumin, and total protein were higher, and urinary excretion of glucose, urea nitrogen, and proteins were lower, in the 1/2Nx than in the Sham group. Remnant kidney weight was two-fold higher in the 1/2Nx than in the Sham group 84 days later. In addition, 1/2Nx resulted in renal tubular dilatation but not in the progression of fibrosis or glomerular lesions. Taken together, these findings indicate that enlarged kidneys were associated with the onset of diabetes and with the resistance to diabetic nephropathy in DEK-DM.
肾脏通过糖异生、胰岛素降解及葡萄糖的肾小管重吸收参与全身葡萄糖代谢的调节。本研究对一种新型2型糖尿病模型（肾脏增大的糖尿病大鼠，DEK）品系的大鼠进行了特征分析。对DEK大鼠进行了组织学和生化分析，以评估其肾脏与高血糖之间的关系。糖尿病DEK大鼠（DEK-DM）的肾脏重量自糖尿病发病后随时间逐渐增加，DEK-DM的肾小球数量高于正常DEK大鼠（DEK-cont）。在DEK-DM中观察到血糖水平与肾脏重量呈正相关。DEK-cont和DEK-DM中相似的肾小球大小和单个肾小球肌酐清除率表明，肾小球肥大和超滤与肾脏增大无关。DEK-DM大鼠进行单侧肾切除术（1/2Nx）后，术后7至28天血糖水平降低，该浓度在术后84天前一直低于假手术组。1/2Nx还改善了全身状况，包括体重增加减少、多尿、多饮和多食。1/2Nx组的血浆钠、总胆固醇、白蛋白和总蛋白浓度较高，而葡萄糖、尿素氮和蛋白质的尿排泄量较低。84天后，1/2Nx组的残余肾脏重量比假手术组高两倍。此外，1/2Nx导致肾小管扩张，但未导致纤维化或肾小球病变进展。综上所述，这些发现表明，在DEK-DM中，增大的肾脏与糖尿病的发生以及对糖尿病肾病的抵抗有关。
