Effect of benazepril on expression of insulin receptor and its substrate-1 protein in renal tissue cell membrane in diabetic rats

AIM: To study effect of benazepril (an ACE inhibitor) on expression of insulin receptor (IR) and its substrate-1 (IRS-1) protein in renal tissue cell membrane in diabetic rats. METHODS: The rats were randomly divided into following groups: control (n=6),streptozotocin induced diabetic (n=7) and diabetic treated with benazepril (n=7). Body weight, kidney weight and kidney weight/body weight were observed after 4 weeks of treatment. ACE activities in plasma, renal tissue were measured by the fluorimetric assay. The expressions of IR and IRS-1 protein were determined by Western blot analysis in renal tissue cell membrane. RESULTS: After 4 weeks of treatment,benazepril significantly ameliorated kidney hypertrophy in diabetic rats. ACE activities in plasma,renal tissue were reduced by approximately 92.00% and 88.77%,respectively. Western blot analysis showed that the expressions of IR and IRS-1 protein were increased by 2.1 and 1.5 folds in renal tissue cell membrane in diabetic rats. However, benazepril reduced expression of IR and IRS-1 protein by 45.74% and 47.66%, respectively. CONCLUSIONS: Increased the expression of IR and IRS-1 protein might be related to abnormally active glucose metabolism in diabetic rat kidney. Down-regulation of expression of IR and IRS-1 protein might be one of important machnisms of Benazepril nephroprotection on diabetic rats.