Effect of L-leucine on glucose turnover in dogs

Abstract

The effect of intravenous administration of L-leucine on glucose turnover was investigated in 8 healthy, anesthetized dogs, each serving as its own control, by 2 isotope dilution technics: the method of successive measured injection of tracer glucose-U-C 14 (3 dogs) and the procedure of priming injection-continuous infusion of tracer (5 dogs). Results obtained with both technics were complementary. In dogs, infusion of 0.5 Gm. L-leucine/Kg. body weight over a period of 30 minutes evoked a consistent and significant reduction in plasma glucose concentration, with mean ± 1 S.E. maximal decrease of 19 ± 1.7 mg. per cent. The intermixing glucose mass was also significantly decreased by an average of 64 mg./Kg. body weight while the apparent distribution space of glucose unaltered. Both rates of glucose appearance, Ra (primarily hepatic production) and disappearance, Rd (tissue utilization) were decreased during infusion of L-leucine with mean maximal diminution of 55 per cent in Ra at t = 5 minutes and 45 per cent in Rd at t = 20 minutes after starting L-leucine; both rates returned to control values after stopping the infusion of L-leucine. The changes in both rates of glucose appearance and disappearance occurred within minutes after starting L-leucine infusion, but the effect on Ra was proportionately greater than the Rd effect, thereby accounting for the decrements in plasma glucose concentration and intermixing glucose mass. These alterations in glucose turnover in dogs are discussed in light of recent findings by others that L-leucine stimulates increased release of insulin.