The Effect of Epinephrine, Glucagon, and the Nutritional State on the Oxidation of Branched Chain Amino Acids and Pyruvate by Isolated Hearts and Diaphragms of the Rat

Abstract

Abstract The effect of epinephrine and glucagon on 14CO2 production from C-1-labeled branched chain amino acids, [1-14C]pyruvate, [1-14C]alanine, and [U-14C]glucose, was studied in isolated diaphragms and perfused hearts. The tissues were obtained from rats fed ad libitum or fasted for 48 hours. Epinephrine (10-4 m) stimulated 14CO2 production from leucine, valine, and alanine by hemidiaphragms of fasted rats incubated without substrate, but not by hemidiaphragms of rats fed ad libitum. The oxidation of histidine was not affected by epinephrine. Epinephrine (10-5 to 10-6 m) stimulated branched chain amino acid oxidation by hearts of fed or fasted rats during perfusion without substrate. The addition of 5.5 mm glucose to the perfusion medium abolished the stimulatory effect of epinephrine on branched chain amino acid oxidation. The addition of pyruvate markedly inhibited the oxidation of branched chain amino acids by perfused hearts, and abolished the stimulatory effect of epinephrine on this process. Glucagon (2 x 10-8 to 5 x 10-9 m) stimulated branched chain amino acid oxidation by hearts of fasted rats perfused without additional substrate. Insulin added to glucagon caused no further stimulation of leucine oxidation. Glucagon did not stimulate leucine oxidation by hearts of fed rats, nor by hearts of fasted rats perfused with glucose (5.5 mm) or pyruvate (20 mm). Glucagon did not affect branched chain amino acid oxidation by diaphragms. N6, O2'-Dibutyryl adenosine 3',5'-monophosphate (10-2 to 10-3 m) was mildly inhibitory. Hearts and diaphragms of fed rats oxidized pyruvate much faster than those of fasted rats. Epinephrine (10-5 to 10-6 m) stimulated the myocardial oxidation of pyruvate and alanine. Epinephrine (10-4 to 10-5 m) stimulated the uptake and oxidation of pyruvate by diaphragms of fed or fasted rats, but diaphragms of fed rats were more responsive to this effect of epinephrine than those of fasted rats. Insulin (1 milliunit per ml) mildly stimulated 14CO2 production from pyruvate by diaphragms of fed rats. Stimulation by 10-5 m epinephrine was greater than that by insulin. In the presence of epinephrine insulin caused no further stimulation. Epinephrine stimulated 14CO2 production from [U-14C]glucose by hemidiaphragms, but did not affect the uptake of glucose from the medium. 14CO2 production from [1-14C]acetate by diaphragms was not affected by epinephrine. Glucagon (2 x 10-8 m) stimulated 14CO2 production from [1-14C]pyruvate by hearts of fed rats, but not by hearts of fasted rats. Glucagon did not stimulate 14CO2 production from [2-14C]pyruvate. Glucagon and insulin stimulated 14CO2 production from [U-14C]glucose at high glucose concentrations (16.5 mm) and the effects of the two hormones were additive. The oxidation of pyruvate and that of the branched chain amino acids by skeletal and heart muscles is regulated by the nutritional state of the animal and is susceptible to hormonal regulation by glucagon, epinephrine, and insulin in hearts, and the latter two hormones in diaphragms. The data suggest that in muscles, the pyruvate dehydrogenase complex is activated in the fed state, and is more responsive to stimulation by epinephrine and glucagon than in the fasted state. On the other hand, branched chain amino acid oxidation by muscles, is more susceptible to stimulation by epinephrine or glucagon in the fasted than in the fed state, and the hormonal stimulation can be suppressed by pyruvate or glucose.