Effects of insulin and starvation on the metabolism of acetate and pyruvate by the perfused rat heart

Abstract

Acetate oxidation by perfused hearts from fed rats accounted for about 75% of the respiratory fuel over the concentration range 1-10 m[image]. Pyruvate was also readily utilized and was the major respiratory fuel when present in the perfusate at concentrations above 0.2 m[image]. At high concentrations (2-10 m[image]) about 30% of the pyruvate removed from the medium was converted into lactate. The uptake of pyruvate by hearts from rats starved for 24 or 48 hrs. was significantly less than that from fed rats, and the proportion of pyruvate converted into lactate was increased. The estimated contribution of pyruvate to the total fuel of respiration was decreased by starvation from 90 to 70%. Addition of insulin to hearts from starved rats restored to normal the rate of pyruvate uptake. Acetate uptake was not affected by starvation, but was increased 20% by insulin. The pyruvate uptake by hearts from fed rats was decreased 20% in the presence of acetate. Glucose uptake in the presence of insulin was decreased 40-45% by acetate or pyruvate, and the conversion of glucose into lactate and glycogen was increased. Under these conditions acetate or pyruvate utilization was decreased by only 10-15%. These studies indicate that increased availability of alternative respiratory fuels inhibit carbohydrate utilization in muscle by competition for the available coenzyme A. The possible relation between this effect and the decreased utilization of carbohydrate by hearts from starved and diabetic animals is discussed.