Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University, Tokyo, Japan.
Laboratory of Biomolecular Chemistry, Nippon Veterinary and Life Science University, Tokyo, Japan.
PLoS One. 2021 May 4;16(5):e0251135. doi: 10.1371/journal.pone.0251135. eCollection 2021.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used to reduce hyperglycemia. The present study investigated the effects of a SGLT2 inhibitor, empagliflozin, on hyperglycemia in a novel rat model of non-obesity type 2 diabetes with enlarged kidney (DEK).
Male DEK rats with non-fasting blood glucose concentrations ≤300 mg/dl and >300 mg/dl were classified as nondiabetic and diabetic, respectively. Groups of nondiabetic (control) and diabetic (DM-cont) rats were fed standard chow for 12 weeks, whereas another group of diabetic (DM-empa) rats was fed standard chow containing empagliflozin (300 mg/kg/day) for 12 weeks. Blood glucose, body weight, glucose tolerance, food and water intake, urinary volume, plasma and urinary biochemical parameters, and bone mineral density were measured, and their kidneys and pancreas histologically analyzed.
Treatment with empagliflozin reduced blood glucose concentration and food intake in diabetic rats, but inhibited loss of adeps renis and led to body weight gain. Empagliflozin attenuated polyuria and polydipsia but increased plasma concentrations of total cholesterol, sodium and total protein toward normal level. Empagliflozin also significantly reduced urinary excretion of proteins and electrolytes and restored bone mineral density and plasma concentrations of valine and isoleucine to normal levels. Moreover, dilation of renal tubules and kidney enlargement were not attenuated in the DM-empa group.
The response of DEK rats to empagliflozin differed from that of other diabetic animal models, suggesting that DEK rats have unique characters for studying and evaluating the multiple biological effects of SGLT2 inhibitors. These findings also indicted that empagliflozin could ameliorate systemic metabolism and improve renal tubule function in diabetic condition.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂被广泛用于降低高血糖。本研究旨在探讨 SGLT2 抑制剂恩格列净对新型非肥胖 2 型糖尿病大鼠（扩大肾脏型，DEK）高血糖的影响。
非禁食血糖浓度≤300mg/dl 和>300mg/dl 的雄性 DEK 大鼠分别被归类为非糖尿病和糖尿病。非糖尿病（对照组）和糖尿病（DM-cont 组）大鼠分别喂食标准饲料 12 周，而另一组糖尿病（DM-empa 组）大鼠喂食含有恩格列净（300mg/kg/天）的标准饲料 12 周。测量血糖、体重、葡萄糖耐量、食物和水的摄入、尿量、血浆和尿液生化参数以及骨矿物质密度，并对其肾脏和胰腺进行组织学分析。
恩格列净治疗可降低糖尿病大鼠的血糖浓度和摄食量，但抑制了肾脂肪丢失并导致体重增加。恩格列净可减轻多尿和多饮，但使总胆固醇、钠和总蛋白的血浆浓度向正常水平增加。恩格列净还可显著减少尿蛋白和电解质的排泄，并使骨矿物质密度和缬氨酸、异亮氨酸的血浆浓度恢复正常。此外，DM-empa 组的肾小管扩张和肾脏增大并未减轻。
DEK 大鼠对恩格列净的反应与其他糖尿病动物模型不同，这表明 DEK 大鼠具有独特的特征，可用于研究和评估 SGLT2 抑制剂的多种生物学效应。这些发现还表明，恩格列净可改善糖尿病状态下的全身代谢并改善肾小管功能。
