Relation of L-Alanine Metabolism to the Action of Triamcinolone in Liver Slices

Abstract

The hypothesis which proposes that glucocorticoids enhance the transport of glycogenic amino acids across the membrane of the liver cell was investigated using a rat liver slice system. In this system, slices respond to glucocorticoids with an increased rate of gluconeogenesis when glucocorticoids are added in vitro. It was concluded that the action of glucocorticoids, specifically triamcinolone (l,4-pregnadiene-9α-fluoro-llβ, 16α, 17α, 21-tetrol-3,20-dione), in this system is not manifested as an acceleration of transport of amino acids (specifically alanine) into the liver cell. The evidence for this conclusion was as follows: 1) L-Alanine disappearance from the incubation medium was not increased in the presence of triamcinolone, although glucose synthesis was stimulated; 2) in contrast, raising the concentration of Lalanine in the incubation medium led to a marked increase in alanine uptake but little or no increase in glucose synthesis; 3) there was no evidence of a sharp concentration gradient between extracellular and intracellular alanine; 4) no rise in intracellular alanine concentration was apparent when glucocorticoids were acting; and 5) by suitable manipulation of experimental conditions it was possible to demonstrate a stimulation of glucose synthesis when pyruvate was substituted for alanine. Thus, the action of triamcinolone, and presumably the action of other glucocorticoids, in this system is not evidenced as an effect upon the transport of alanine nor upon its conversion to pyruvate, but primarily at some reaction or reactions involved in the conversion of pyruvate to glucose. (Endocrinology75: 602, 1964)