Influence of beta-hydroxybutyrate infusion on glucose and free fatty acid metabolism in dogs

Authors:
  • JSJ. H. Shaw
    J. H. Shaw
  • RWR. R. Wolfe
    R. R. Wolfe
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Abstract
The effect of infusion of DL-.beta.-hydroxybutyrate (BOHB) (30 .mu.mol/kg per min) on glucose and free fatty acid (FFA) metabolism was investigated by means of the primed constant infusion of [U-14C]glucose and [1,2-13C]palmitic acid. The role of the hormonal response to the ketone infusion was assessed by controlling the hormone levels pharmacologically. In 1 group hormones were not controlled, while in the other 2 groups insulin and glucagon were maintained at constant levels by infusion of somatostatin, insulin and glucagon at constant rates. In 1 of these hormonally controlled groups, combined .alpha.- and .beta.-adrenergic blockade was also employed. BOHB infusion increased total ketone concentration .apprx. 10-fold and, when hormones were not controlled, induced a significant increase in glucagon concentration. Regardless of hormonal status, elevation of the ketone levels decreased the rate of glucose production and FFA appearance. Glucose oxidation decreased in proportion to the reduction in the rate of glucose uptake in all groups. When sympathetic activity was not blocked an increase in the percent of FFA uptake oxidized enabled the percent CO2 production from FFA oxidation to remain constant despite the decrease in FFA uptake. When sympathetic activity was blocked the increase in the percent of FFA uptake oxidized observed in the other groups was prevented. An elevation in ketone levels directly affects glucose and FFA metabolism independent of changes in insulin and glucagon levels and sympathetic activity.

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