Hormonal regulation of incorporation of alanine-U-14C into glucose in human fetal liver explants. Effect of dibutyryl cyclic AMP, glucagon, insulin, and triamcinolone

Abstract

Incorporation of alanine-U-14C into glucose and liver glycogen increased linearly over sixty-five hours in culture of human fetal liver explants. This rate of incorporation was stimulated two- to tenfold by incubation with N6,2'O-dibutyryl adenosine 3'-5:cyclic monophosphate (dibutyryl cyclic AMP) (0.1 mM) plus theophylline (0.5 mM) or glucagon (7.5 mug./ml.) plus theophylline. No apparent lag period was detected, and the hormonal effect continued throughout the observation period. Insulin (1 U./ml.) significantly decreased both the basal rate of incorporation and the stimulated rate resulting from dibutyryl cyclic AMP or glucagon incubation. These effects were observed at both high (10mM) and low (2.8 mM) media glucose and from both 2.3 muM and 5 mM alanine-U-14C. Triamcinolone (20 mug./ml.) alone stimulated the rate of alanine-U-14C incorporation into glucose, whereas triamcinolone in the presence of dibutyryl cyclic AMP produced an increase in incorporation greater than the sum of the individual effects. The basal incorporation of alanine-U-14C into glucose by these human fetal liver explants provide a rate of approximately 4 nmoles glucose/gm. min, which is discussed in relation to the physiologic needs of the fetus and newborn.