Effect of Free Fatty Acids and Ketone Bodies on Glucose Uptake and Oxidation in the Dog

Abstract

Nineteen anesthetized dogs were infused at a constant rate with glucose, glucose-U-¹⁴C and insulin for 5 hr. Arterial concentrations of glucose, acetoacetate (AcAc), β-hydroxybutyrate (BOHB) and free fatty acids (FFA) and the specific activity (SA) of expired CO₂ were followed throughout the study. Experiments were divided into three groups.

In the first group (control experiments), no other exogenous substrate was provided to the animals. Glycemia remained in the normal range and was steady, indicating that glucose uptake was equal to the rate of infusion. About 25% of the infused glucose was promptly oxidized yielding 46% of the total CO₂ production.

In the second group of studies, the FFA level was increased during the last 2 hr of the experiment by the concomitant administration of a triglyceride emulsion and heparin. Under these conditions, the fractional removal rate of glucose was reduced by 42% and the contribution of glucose to total CO₂ production was inhibited by 24% when compared to control values.

In the third group of studies, a similar experimental model was used to test the influence of increased ketone levels on glucose metabolism. The infusion of AcAc resulted in a 18% reduction in the fractional removal rate of glucose and in a 41% reduction in glucose oxidation.

It is concluded that FFA and ketone bodies inhibit glucose uptake and oxidation in insulinized animals.

Key words

¹⁴C-Glucose - Free Fatty Acids - Acetoacetate - Glucose Oxidation - Energy Metabolism