Cross-talk related to insulin and angiotensin II binding on myocardial remodelling in diabetic rat hearts.
This study focused on the regulation and affinity modulation of angiotensin II (Ang II) binding to its receptor subtypes (AT(1)- and AT(2)-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 t to normal on both CE and CM. Western blot results for AT(1)-receptor density showed an increase in diabetics compared to normal with no normalising effect with insulin treatment. The AT(1)-receptor density was normalised in the diabetic groups treated with losartan +/- insulin. Results for AT(2)-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.
Maharsy
Wael M
WM
Department of Physiology, American University of Beirut, Beirut, Lebanon.
Kadi
Lina N
LN
Issa
Nahla G
NG
Bitar
Khalil M
KM
Der-Boghossian
Asdghig H
AH
Abrahamian
Roy
R
Bikhazi
Anwar B
AB
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D006321:Heart / Q000033:anatomy & histology / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism* / Q000627:therapeutic use; D019808:Losartan / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000517:prevention & control*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D020239:Receptor Cross-Talk / Q000502:physiology*; D011972:Receptor, Insulin / Q000502:physiology; D011945:Receptors, Angiotensin / Q000502:physiology; D012016:Reference Values
D000889:Anti-Arrhythmia Agents; D001786:Blood Glucose; D007328:Insulin; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D011972:Receptor, Insulin; D019808:Losartan