Influence of feeding and intracoronary dose on insulin-mediated relative akt phosphorylation in the porcine myocardium.

Aims: Insulin promotes Akt-dependent prosurvival signaling and reduces experimental ischemia reperfusion injury, but its clinical impact has been limited. Further understanding of the interplay between insulin and Akt in the myocardium of relevant large animal models is needed. We aimed to investigate (1) Akt phosphorylation, (2) influence of feeding state, and (3) impact of dose on the Akt response following intracoronary insulin administration in the nonischemic porcine heart.

Methods: Pigs fed 2 h preprocedure received 0.1 U (unit) or 1.0 U of insulin in the left coronary artery and fasting pigs 0.1 U. Left and right ventricle tissues harvested 15 min postinsulin administration were analyzed for Akt phosphorylation by densitometric analyses of total Akt and phosphorylated Akt immunoblots expressed as a ratio and normalized against left auricle biopsies at baseline.

Results: Median relative Akt phosphorylation across all biopsy locations increased significantly from baseline in both fasting and fed animals after insulin infusion: 371.4% (P < 0.001) in the fasting-0.1 U insulin group, 202.7% (P = 0.003) in the fed-1.0 U group and 131.5% (P < 0.001) in the fed-0.1 U group. The increase was significantly higher for the fasting-0.1 U and the fed-1.0 U groups as compared with the fed-0.1 U group. Baseline serum glucose in fed and fasting pigs was 6.3 ± 0.3 versus 5.2 ± 0.4 mm (P = 0.050), respectively.

Conclusions: Preexperimental feeding attenuates the median relative rise in Akt phosphorylation mediated by exogenous insulin in the porcine heart, and higher insulin doses are therefore required in fed compared with fasting animals.