Sitagliptin ameliorates diabetic nephropathy by upregulating renal nephrin and podocin expression through modulation of adipokines levels.

Diabetic nephropathy is the leading cause of end-stage renal failure, but the effectiveness of currently available strategies for preventing diabetic nephropathy remains unsatisfactory. This study was designed to evaluate the changes in adipokines levels caused by dipeptidyl peptidase-4 inhibitor sitagliptin therapy as one of the possible mechanisms of sitagliptin's amelioration of diabetic nephropathy. Twenty-four male Wistar rats weighing 180-200 g were taken and divided into three groups, that is, control, diseased, and treatment group. High-fat diet and streptozotocin-induced Type 2 diabetic rats were divided into diseased and treatment groups. The treatment group was given sitagliptin orally, 10 mg/kg per day for 6 weeks. Serum glucose, serum insulin, serum blood urea nitrogen, serum creatinine, and 24-h urinary protein levels were measured in serum and urine samples. mRNA expression levels of podocin, nephrin, and adipokines in renal tissues were determined. Results showed that sitagliptin treatment effectively reduced serum glucose, serum creatinine, serum blood urea nitrogen, and 24-h proteinuria, along with partial prevention of insulinopenia, in the treatment group as compared to the diseased group. The renal mRNA expression levels of podocin, nephrin, and adiponectin were significantly upregulated, while those of leptin and resistin were significantly downregulated in the diabetic rats receiving sitagliptin therapy compared to the non-treated diabetic rats. Based on these findings, it is suggested that sitagliptin, via mediating the modulation of adipokines levels, upregulates renal nephrin and podocin expression, which leads to the amelioration of diabetic nephropathy.