INHIBITION OF GLUCONEOGENESIS BY HYDRAZINE ADMINISTRATION IN RATS

¹ Physiological Chemistry Section, United States Air Force School of Aerospace Medicine, Brooks Air Force Base, Texas

Hydrazine, a known hypoglycemic agent, was studied to determine the mechanisms of its effects on carbohydrate metabolism. Rats previously fasted for 24 hr were injected i.v. with hydrazine, and blood glucose, lactate and pyruvate were measured. As previously described in dogs, hydrazine caused hypoglycemia and elevation of blood lactate and pyruvate in rats. Injection of 1 mmol of alanine, aspartate or pyruvate did not prevent the hypoglycemia. The effect of hydrazine on gluconeogenesis was studied by determining the incorporation of C¹⁴ into blood glucose 1 hr after administration of uniformly labeled L-alanine-C¹⁴, uniformly labeled L-aspartate-C¹⁴ or pyruvate-3-C¹⁴. Incorporation was measured in control rats and in rats injected i.v. 5 min previously with hydrazine. In the latter group, C¹⁴-incorporation into blood glucose from all three precursors was only approximately 25% of that observed in the control group. When pyruvate-3-C¹⁴ was administered, the specific activity of blood pyruvate in the rats injected with hydrazine exceeded the specific activity of blood pyruvate in controls. These findings demonstrate that hydrazine inhibited gluconeogenesis and simultaneously caused hypoglycemia and elevated blood lactate and pyruvate. No incorporation of C¹⁴ into glycogen was found in hydrazine-treated animals, probably because of decreased gluconeogenesis and increased glycogenolytic activity.