OBJECTIVE: To investigate the signaling pathway involved in the insulin-elicited anti-apoptotic effect during @entity741 and reperfusion (MI/R) in vivo. METHODS: Male @entity35 were anesthetized and subjected to 30 min of @entity741 followed by 4h-reperfusion. @entity35 were randomly treated with intravenous infusion of saline (vehicle, 4 ml.kg(-1).h(-1)), insulin (60 U/L), or insulin + @entity2307 5 min before reperfusion and continuing throughout the 4h-reperfusion period. Cardiac myocyte apoptosis was determined both qualitatively and quantitatively by DNA laddering and terminal deoxynucleotidyl transferase-mediated @entity1977 nick-end labeling (TUNEL) methods. Myocardial @entity842 (NO) was measured by using NO-specific chemiluminescence detector. Activations of Akt and @entity12220 (MAPK) were determined by kinase activity assays using corresponding kinase activity assay kits (Cell Signaling). RESULTS: In the vehicle-treated @entity35 , MI/R caused significant cardiac myocyte apoptotic death. Treatment with insulin produced a significant anti-apoptotic effect as evidenced by a marked reduction of apoptotic index [(8.0 +/- 2.9)% vs. (19.3 +/- 4.6)% of vehicle, P < 0.01] and decreased formation of myocardial DNA fragmentation. In addition, insulin treatment produced 2.7-fold increase (P < 0.01) of myocardial Akt activity and 28% increase of myocardial NO production (P < 0.05), while p38 MAPK activity changed insignificantly as compared with that of vehicle (P > 0.05). Both insulin-induced Akt activation and anti-apoptotic effect could be abrogated by @entity2307 , a @entity4357 (PI) 3-kinase inhibitor. CONCLUSION: In vivo treatment with insulin at the initial of reperfusion significantly reduced postischemic apoptotic death via the PI3-kinase-Akt signaling pathway. Akt, but not p38 MAPK, activation plays a key role in the insulin-induced anti-apoptotic effect in MI/R.

[Anti-apoptotic effect of insulin in XXXX -reperfusion and its principal signaling pathway].

@entity1977 :: ('CHEBI:17625', 'Chemical') :: ['dUTP'] @entity2307 :: ('MESH:C009687', 'Chemical') :: ['wortmannin'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity741 :: ('MESH:D017202', 'Disease') :: ['myocardial ischemia'] @entity35 :: ('10116', 'Species') :: ['Sprague-Dawley rats', 'Rats', 'rats'] @entity12220 :: ('81649(Tax:10116)', 'Gene') :: ['p38 mitogen-activated protein kinase'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidylinositol']
@entity741 :: (MESH:D017202,Disease) :: ['myocardial ischemia']
