Effect of Insulin and Losartan on Modulation of Insulin-Like Growth Factor 1 Receptor at Heart Level in Diabetic Rats

This study investigates insulin-like growth factor-1 receptor (IGF-1R) modulation in hearts of streptozotocin- induced diabetic rats treated with insulin/angiotensin-II receptor subtype-1 blocker (AR1B), losartan. Male rats were di- vided into: normal (N), losartan-treated normal (NL), diabetic (D), insulin-treated diabetic (DI), losartan-treated diabetic (DL), and insulin/losartan co-treated diabetic (DIL) groups. Thirty days post-treatment, rats underwent heart perfusion us- ing (I 125 )-labeled IGF-1 to assess receptor-binding affinity on coronary endothelial cells (CE) and cardiomyocytes (CM). This revealed an increase in binding affinity of IGF-1 to its receptor on CE in all groups compared to N. On CM, binding affinity increased in D, DI, and DL compared to N, but was almost normalized in DIL. Western blot analyses and immu- nohistochemistry done on heart tissues showed decrease in IGF-1R density in DIL versus remaining groups. These results demonstrate a complex interaction between insulin, angiotensin-II, and IGF-1, and mass blockade of myocardial remodel- ing by AR1B treatment in diabetic state.