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

摘要

This study investigates insulin-like growth factor-1 receptor (IGF-1R) modulation in hearts of streptozotocininduceddiabetic rats treated with insulin/angiotensin-II receptor subtype-1 blocker (AR1B), losartan. Male rats were dividedinto: 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 using[I125]-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, bindingaffinity increased in D, DI, and DL compared to N, but was almost normalized in DIL. Western blot analyses and immunohistochemistrydone on heart tissues showed decrease in IGF-1R density in DIL versus remaining groups. These resultsdemonstrate a complex interaction between insulin, angiotensin-II, and IGF-1, and mass blockade of myocardial remodelingby AR1B treatment in diabetic state.