Alanine and Gluconeogenesis in Man: Effect of Ethanol

Alanine disappearance and disposal were studied in six normal human volunteers with l-alanine-U-14C and the effect of ethanol on the metabolism of alanine was studied with the oral administration of bonded whiskey.

Abstract

Alanine disappearance and disposal were studied in six normal human volunteers with l-alanine-U-14C. Fifty μCi of l-alanine-U-14C was administered as a single in injection on two separate occasions. The effect of ethanol on the metabolism of alanine was studied with the oral administration of bonded whiskey (19.6 g of ethanol followed 1 hr later by 9.8 g). In control studies, the plasma glucose and lactate concentrations remained constant during the experimental period. The half-life (t½) of plasma alanine radioactivity was 22.8 min ± 1.2 (sem, n = 6). 14C appeared promptly in glucose and reached plateau values within 30–60 min. 12.5% ± 0.9 of the administered dose of alanine-U-14C was recovered in glucose while 26.5% ± 3.0 of the administered dose was recovered in lactate. The t½ of plasma lactate SA after the injection of alanine U-14C was 32.7 min ± 1.1. During the administration of ethanol, plasma glucose concentrations were not altered but lactate concentrations increased from 0.98 ± 0.07 to 1.58 ± 0.09 mM. Alanine t½ was 23.1 min ± 1.8. Alanine-14C recovery in glucose was reduced by 75% to 3.3% ± 0.5 while recovery in lactate increased by 250% to 70.6% ± 6.7. Lactate t½ was prolonged to 42.5 min ± 3.7. Plasma alanine concentrations were reduced 25% by ethanol from 330 ± 38 to 248 ± 14 μm. The significant decline in plasma alanine suggests that alterations in substrate availability may be as important, or more important, in mediation of the inhibitory effects of ethanol on gluconeogenesis than the direct effects of ethanol on hepatic uptake and utilization of glycogenic substrate.