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.
Highlights
EJect of Epinephrine and Nutritional State of Animal on 14COz Production from Branched Chain Amino Acids, Alanine and Histidine, by Rat Hemidiaphragms (Table I)-Hemidiaphragms obtained from rats fed ad libitum were incubated for 1 or 2 hours with [lJ4C]valine with or without the addition of epinephrine (20 pg per ml)
We have previously shown that this dose of insulin stimulates leucine oxidation by hearts obtained from fasted rats perfused without glucose and glucagon (3)
Our data support the observation (6, 7, 9) that the rate of pyruvate oxidation by skeletal and cardiac muscle is dependent on the nutritional state of the animal
Summary
Male rats of the Wistar strain were used. The animals had free access to food (Wayne Lab-blocks) and water up to the time of the experiment, or were deprived of food for 48 hours prior to the experiment. In studies with perfused hearts rats weighing 180 to 275 g were used. In each experiment control and experimental aninlals were paired within 10 g of body weight, and perfused in alternate order with control or experimental media. The rats used for studies of isolated diaphragms weighed 100 to 200 g and were within &lo g in individual experiments. Rats were killed by decapitation with a guillotine (Harvard Apparatus Co.)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.