Empagliflozin ameliorates symptoms of diabetes and renal tubular dysfunction in a rat model of diabetes with enlarged kidney (DEK)

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.