The Open Drug Delivery Journal

2007, 1 : 1-6
Published online 2007 July 12. DOI: 10.2174/1874126600701010001
Publisher ID: TODDJ-1-1

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

Anwar B. Bikhazi , Wael M. Maharsy , Lina N. Kadi , Nahla G. Issa , Ghinwa M. Barakat , Nuha Nuwayri-Salti , George K. Karam , Omar A. Batal and Khalil M. Bitar
Department of Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

ABSTRACT

This study investigates insulin-like growth factor-1 receptor (IGF-1R) modulation in hearts of streptozotocininduced diabetic rats treated with insulin/angiotensin-II receptor subtype-1 blocker (AR1B), losartan. Male rats were divided 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 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, binding affinity increased in D, DI, and DL compared to N, but was almost normalized in DIL. Western blot analyses and immunohistochemistry 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 remodeling by AR1B treatment in diabetic state.

Keywords:

Insulin-dependent-diabetes-mellitus, insulin receptor, insulin-like growth factor 1 receptor, receptor regulation, cardiomyopathy.