Evidence for an effect of insulin on the peripheral utilization of ketone bodies in dogs

E. O. Balasse; R. J. Havel

doi:10.1172/JCI106551

Evidence for an effect of insulin on the peripheral utilization of ketone bodies in dogs

E. O. Balasse and R. J. Havel

Published April 1, 1971 - More info

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Abstract

The rates of transport and oxidation of acetoacetate have been measured in seven anesthetized, pancreatectomized, ketotic dogs using a constant infusion of acetoacetate-3-¹⁴C. Control experiments were performed in 14 normal dogs. In addition to the acetoacetate-¹⁴C, the latter were infused at a constant rate with varying amounts of unlabeled acetoacetate so as to obtain a range of ketone transport (26-65 μmoles/min·kg) comparable with that observed in the diabetic dogs (21-41 μmoles/min·kg). The specific activities of acetoacetate and β-hydroxybutyrate in blood became equal during the infusion of labeled acetoacetate, indicating that the net transport of acetoacetate represents that of total ketones. In each group, the concentration of ketones was an exponential function of the rate of transport, but for any value below 30 μmoles/min·kg, ketone concentration in the diabetic dogs was about 3 times that in normal dogs, indicating an impairment of mechanisms for utilizing ketones in insulin deficient animals. Maximal capacity to utilize ketones in diabetic dogs was slightly more than half that of normal ones. A similar fraction (32-63%) of the infused ¹⁴C appeared in respiratory CO₂ in the two groups and was independent of the rate of transport. In seven of the normal dogs, administration of insulin and glucose increased removal of the infused ketones and increased the fraction of ¹⁴C appearing in respiratory CO₂. These results demonstrate that utilization of ketones in extrahepatic tissues is influenced by insulin; impaired utilization contributes to diabetic ketosis and is probably essential to the production of severe ketoacidosis.