Operation of the glucose-fatty acid cycle after glycogenolysis induced by treatment with nicotinic acid

Abstract

The time courses of liver glycogen, blood glucose, plasma free fatty acids, ketone bodies, immunoreactive insulin, and glucagon and liver cyclic AMP concentrations after treatment with nicotinic acid were investigated. The administration of nicotinic acid caused a rapid glycogen depletion which was followed by a decrease in blood glucose and a rise in plasma free fatty acids and ketone bodies. Supplementation of nicotinic acid with theophylline accelerated the glycogen depletion, the onset of hypoglycemia, and the rise in free fatty acids and ketone bodies. Liver cyclic AMP doubled 15 min after the administration of nicotinic acid and the effect of theophylline was synergistic. The plasma immunoreactive insulin/glucagon ratio decreased after treatment with nicotinic acid. The rise in plasma free fatty acids and ketone bodies which occurred after the administration of nicotinic acid was prevented by the administration of glucose or insulin. These results suggest that the increase in plasma free fatty acids observed after treatment with nicotinic acid is a consequence of the operation of the “glucose-fatty acid cycle” promoted by the decrease in the plasma insulin/glucagon ratio.