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Journal of Renin-Angiotensin-Aldosterone System
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Cross-talk related to insulin and angiotensin II binding on myocardial remodelling in diabetic rat hearts

Wael M Maharsy

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 ({tau}=1/k-n) to its receptor subtypes on CE and CM. Diabetes decreased {tau} value on CE and increased it on CM as compared to normal. In DL group, the {tau} value decreased on CE but was normalised on CM. Insulin treatment alone (DI) or with losartan (DIL) restored {tau} 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

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


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