Renal Insulin Sensitizing Effect of Exenatide in a High-fat Diet Obesity Rat Model

Abstract

Insulin receptor (IR) is expressed throughout the nephron and is vital for the renal function. Renal complications may occur in insulin-resistant states. The aim of the present study was to find out the possible renoprotective effect of exenatide in rats fed a high-fat diet (HFD) and whether this therapeutic approach resulted in regulation of renal IR gene expression. Rats were fed HFD for 16 weeks and received exenatide (10 μg/kg, SC/d/ 4 weeks). The body weight, insulin resistance and lipid profile were measured. The renal function and histopathological changes were assessed. Also, IR gene expression was analyzed in the renal homogenate. HFD rats showed systemic alterations including obesity, insulin resistance, dyslipidemia and renal impairment. The renal injury was associated with down regulation of renal IR gene expression and minimal cytoplasmic reaction to insulin receptor immunohistochemical staining. The systemic and renal alterations induced by HFD were alleviated by exenatide with marked up regulation of renal IR gene expression. In conclusion, exenatide may be a novel therapeutic agent for renal damage induced by obesity. This renoprotective effect is partly produced by up-regulation of renal IR gene in addition to the control of body weight, insulin resistance and dyslipidemia.