AJP - Endocrinology and Metabolism, Vol 247, Issue 6 756-E764, Copyright © 1984 by American Physiological Society
Influence of beta-hydroxybutyrate infusion on glucose and free fatty acid metabolism in dogs
J. H. Shaw and R. R. Wolfe
We have investigated the effect of infusion of DL-beta-hydroxybutyrate
(BOHB) (30 mumol X kg-1 X min-1) on glucose and free fatty acid (FFA)
metabolism 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 one group hormones were not controlled, while in the other two groups
insulin and glucagon were maintained at constant levels by infusion of
somatostatin, insulin, and glucagon at constant rates. In one of these
hormonally controlled groups, combined alpha- and beta-adrenergic blockade
was also employed. BOHB infusion increased total ketone concentration
approximately 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. However, when sympathetic activity was
blocked the increase in the percent of FFA uptake oxidized observed in the
other groups was prevented. We conclude from these studies that an
elevation in ketone levels directly affects glucose and FFA metabolism
independent of changes in insulin and glucagon levels and sympathetic
activity.
