Effect of insulin and epinephrine on the carbohydrate metabolism and adenylate cyclase activity of rhesus fetal muscle.

Abstract

Extract: Carbohydrate metabolism of skeletal muscle from rhesus fetuses at 58% of gestation (95 days) is sensitive to epinephrine in vitro. Epinephrine increased lactate production and decreased glucose uptake, 14C-lactate production, glycogen content, and 14C-glycogen formation as well as 14CO2 production. These responses to epinephrine are similar to those in adult muscle. However, in some cases the magnitude of these responses appears lower in fetal muscle. The content of cyclic 14C-adenosine 3‘,5’-monophosphate (cyclic 14C-AMP) was about 2.5-fold higher in the 100-day fetal muscle than in the adult. Epinephrine stimulated adenylate cyclase activity almost threefold in fetal and fourfold in adult muscle. When incubated with muscle from 85-day fetal monkeys, insulin increased glucose uptake, lactate and lactate-14C production, and 14CO2 production; the greatest effect was found in the increased incorporation of labeled glucose into glycogen. Both synthetase I and phosphorylase a activities were present at 78–80 days of fetal age. Our data show that as early as about 58% of term the carbohydrate metabolism of fetal rhesus muscle in vitro is sensitive to epinephrine and that the hormone probably acts through the adenylate cyclase and the “second messenger” system of cyclic AMP as it does in adult muscle.Speculation: Our data offer indirect evidence that insulin and epinephrine mediate glycogen metabolism via cyclic AMP in rhesus fetal muscle as early as 85 days of gestational age (52% of term) and that these hormones operate through similar enzyme systems in fetal and adult muscle. It is possible that glycogen synthetase and phosphorylase, or other enzymes mediating the cyclic AMP response, are not identical in fetal and adult muscle; fetal isoenzyme patterns for muscle lactate dehydrogenase differ markedly from those of the adult. However, it is difficult to reconcile the existence of major differences in the enzyme milieu in fetal and adult muscle with the similar overall actions of epinephrine and insulin on glycogenesis and glycogenolysis demonstrated in our experiments.