Hyperinsulinemia increases glucose uptake and oxidation and improves contractile function during ischemia despite no effect on fatty acid oxidation or lactate production

Abstract

Ex vivo studies in rodent hearts show that increased glucose metabolism by hyperinsulinemia during ischemia improves cardiac mechanical efficiency. This protective effect has not been demonstrated in vivo, and it is unclear if it is dependent upon inhibition of fatty acid oxidation (FAO). In the present study we tested the hypothesis that stimulation of glucose uptake and oxidation by insulin infusion would improve ventricular wall motion independent of changes in FAO. Measurements were made in anesthetized open-chest swine hearts subjected to 40 mins of regional myocardial ischemia. Pigs were either treated with a high dose of i.v. insulin (art. conc of 4219 pM) initiated 50 min before ischemia, or were untreated (6 pM) (n=8/group). The insulin group received i.v. glucose to maintain arterial levels at ~6 mM. Glucose and FAO were measured with 14C-glucose and 3H-oleate, and regional myocardial external power was calculated from the LV pressure - segment length loop area as assessed by sonomicrometry. Results showed that insulin infusion increased glucose uptake and oxidation, but did not significantly effect the total lactate efflux during ischemia. Hyperinsulinemia showed a strong trend towards increased cardiac power index and myocardial efficiency. There were no significant differences in the MVO2, FAO and tissue ATP content between two groups under ischemic condition. Conclusion Enhanced glucose oxidation increased the myocardial energy efficiency and provided protective effect to the heart during ischemia. This effect was not dependent upon inhibition of FAO nor increased lactate production.