Inosine causing insulin release and increased myocardial uptake of carbohydrates relative to free fatty acids in dogs

Abstract

The aim of the present study was to determine the effect of i.v. inosine on myocardial substrate uptake and function in the in situ dog heart. Inosine was infused i.v. at a rate of 5 mg kg min-1 in eight closed-chest pentobarbital anaesthetized dogs. Inosine caused a 46% decrease (P less than 0.01) in plasma free fatty acids (FFA), a 15% decrease (P less than 0.05) in plasma glycerol, an 18% decrease (P less than 0.05) in plasma glucose and a 46% increase (P less than 0.01) in blood lactate. This was associated with a 55% decrease (P less than 0.01) in myocardial FFA uptake and a 72% increase in lactate uptake, while glucose uptake remained unchanged. These metabolic changes were associated with a five-fold increase (P less than 0.05) in arterial insulin. Inosine caused an 18% increase (P less than 0.01) in myocardial blood flow without changing MVO2. There was a 33% increase (P less than 0.01) in LV dP/dtmax, a decrease in LVEDP from 4.9 +/- 0.9 (mean +/- SEM) to 0.9 +/- 0.3 mmHg (P less than 0.05) and a 24% decrease (P less than 0.01) in systemic vascular resistance. Inosine caused a transient 38% increase (P less than 0.05) in pulmonary vascular resistance. In conclusion, in addition to a positive inotropic effect and vascular effects inosine was found to cause release of insulin and to shift myocardial metabolism towards increased uptake of carbohydrates relative to FFA.