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Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus. Our study aims to demonstrate the effectiveness of exenatide, glucagon like peptide-1 receptor agonist, on insulin release and renal functions in type 2 diabetes mellitus (T2DM) rats enduring DN. T2DM was induced in male wistar-albino rats by single streptozotocin injection (40 mg/kg, i.p.) followed by high fat diet for 10 weeks, while the treatment group received exenatide injection (10 μg/kg/day, i.p.) one week after STZ injection along for 9 weeks. Animals were monitored by periodic biochemical testing of fasting serum glucose (FSG), cystatin-C, creatinine and urinary protein levels. At the end of the study (10 weeks) serum total nitrite/nitrate (NOx), adiponectin, C-peptide and amylase activity were investigated. Renal total triglycerides; hydroxy proline (HP), and DNA fragmentation were estimated, as well as renal enzymatic activity and mRNA expression level of glucose-6-phosphatase. Exenatide showed significant reduction in FSG, serum creatinine, cystatinC, and urinary protein levels in diabetic rats. It favored increased serum NOx, serum adiponectin as well as C-peptide which reflects improving in insulin sensitivity and release respectively. Further, exenatide diminished renal DNA fragmentation, decreased renal triglyceride, HP contents, and glucose-6-phosphatase enzyme activity and expression levels in diabetic rats. Our data donate further credence for the effectiveness of exenatide against diabetic renal complications, through different aspects including reduction of renal DNA fragmentation and gluconeogenesis in addition to the previously reported mechanisms.

Exenatide prevents diabetic nephropathy in a rat model of type 2 diabetes mellitus (fat-fed and streptozotocin-treated rats)