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Cross-talk related to insulin and angiotensin II binding on myocardial remodelling in diabetic rat hearts

Departments of Physiology, American University of Beirut, Beirut, Lebanon

Lina N Kadi

Departments of Physiology, American University of Beirut, Beirut, Lebanon

Nahla G Issa

Departments of Physiology, American University of Beirut, Beirut, Lebanon

Khalil M Bitar

Departments of Physics, American University of Beirut, Beirut, Lebanon

Asdghig H Der-Boghossian

Departments of Physiology, American University of Beirut, Beirut, Lebanon

Roy Abrahamian

Internal Medicine, American University of Beirut, Beirut, Lebanon

Anwar B Bikhazi

Departments of Physiology, American University of Beirut, Beirut, Lebanon, ab04{at}aub.edu.lb

This study focused on the regulation and affinity modulation of angiotensin II (Ang II) binding to its receptor subtypes (AT1- and AT2-receptor) in the coronary endothelium (CE) and cardiomyocytes (CM) of Sprague-Dawley male rats in normal (N), normal treated with losartan (NL), streptozotocin-induced diabetic (D), insulin-treated diabetic (DI), losartan-treated diabetic (DL), and diabetic co-treated with insulin and losartan (DIL). Heart perfusion was used to estimate Ang II binding affinity (=1/k-n) to its receptor subtypes on CE and CM. Diabetes decreased value on CE and increased it on CM as compared to normal. In DL group, the value decreased on CE but was normalised on CM. Insulin treatment alone (DI) or with losartan (DIL) restored to normal on both CE and CM.Western blot results for AT -receptor density showed an increase in diabetics compared to normal with no normalising effect with insulin treatment.The AT1-receptor density was normalised in the diabetic groups treated with losartan +/- insulin. Results for AT₂ receptor regulation revealed a significant difference between untreated (D) and losartan-treated (DL, DIL) diabetic groups.All of these data show the interrelated pathway and cross-talk between insulin and Ang II system indicating potentially negative effects on the diabetic heart.

Key Words: insulin-dependent-diabetes-mellitus • insulin receptor • angiotensin-II receptors • receptor regulation • cardiomyopathy

Journal of Renin-Angiotensin-Aldosterone System, Vol. 8, No. 2, 59-65 (2007)
DOI: 10.3317/jraas.2007.011


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