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

• Published in: Journal of the renin-angiotensin-aldosterone system 2007-06, Vol.8 (2), p.59-65
• Main Authors: Maharsy, Wael M, Kadi, Lina N, Issa, Nahla G, Bitar, Khalil M, Der-Boghossian, Asdghig H, Abrahamian, Roy, Bikhazi, Anwar B
• Format: Article
• Language: English
• Subjects: Angiotensin II - metabolism; Animals; Anti-Arrhythmia Agents - therapeutic use; Blood Glucose - drug effects; Blood Glucose - metabolism; Body Weight - drug effects; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - physiopathology; Heart - anatomy & histology; Heart - physiopathology; Insulin - metabolism; Insulin - therapeutic use; Losartan - therapeutic use; Myocardial Infarction - prevention & control; Organ Size - drug effects; Rats; Receptor Cross-Talk - physiology; Receptor, Insulin - physiology; Receptors, Angiotensin - physiology; Reference Values
• ISSN: 1470-3203; 1752-8976
• DOI: 10.3317/jraas.2007.011

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