Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry

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 by single streptozotocin (STZ) injection (40 mg / kg, i.p.) followed by high fat diet (HFD) for 10 weeks. Male wistar-albino rats were randomly divided into three groups: a normal control group, a HFD-STZ induced DN model group, and a DN plus exenatide (10 æg / kg / day, i.p.) treatment group. 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, cystatin- C, 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

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