Effect of isoproterenol on amino acid levels and protein turnover in skeletal muscle.

The role of elevated plasma epinephrine concentrations in the regulation of plasma leucine kinetics and the contribution of ,8-receptors were assessed in man. Epinephrine (50 ng/kg per min) was infused either alone or combined with propranolol (f,-blockade) into groups of six subjects fasted overnight; leucine flux, oxidation, and net plasma leucine forearm balance were determined during 180 min. Constant plasma insulin and glucagon concentrations were maintained in all studies by infusing somatostatin combined with insulin and glucagon replacements. Plasma leucine concentrations decreased from baseline during epinephrine infusion by 27±5 gmol/liter (P < 0.02) due to a 22±6% decrease in leucine flux (P < 0.05 vs. controls receiving saline) and to an increase in the metabolic clearance rate of leucine (P < 0.02). Leucine oxidation decreased by 36±8% (P < 0.01 vs. controls). fl-Blockade abolished the effect of epinephrine on leucine flux and oxidation. Net forearm release of leucine increased during epinephrine (P < 0.01), suggesting increased muscle proteolysis; the fall of total body leucine flux was therefore due to diminished proteolysis in nonmuscle tissues, such as splanchnic organs. Nonoxidative leucine disappearance as a parameter of protein synthesis was not significantly influenced by epinephrine. Plasma glucose and FFA concentrations increased via f,-adrenergic mechanisms (P < 0.001). The results suggest that elevation of plasma epinephrine concentrations similar to those observed in severe stress results in redistribution of body proteins and exerts a whole body protein-sparing effect; this may counteract catabolic effects of other hormones during severe stress.

Section: Discussionmentioning

confidence: 99%

Elevation of plasma epinephrine concentrations inhibits proteolysis and leucine oxidation in man via beta-adrenergic mechanisms.

Kraenzlin¹,

Keller²,

Keller³

et al. 1989

“…Glucagon appears to be devoid of any direct influence on skeletal muscle protein metabolism (36). Similarly, catecholamines are unlikely to play a major protein catabolic role, since they appear to actually inhibit proteolysis and amino acid release from skeletal muscle (37,38). It has been postulated, nevertheless, that catecholamines may exert an indirect protein catabolic effect by inhibiting insulin secretion (7); this, in turn, could potentiate any primary protein catabolic stimulus.…”

Section: Discussionmentioning

confidence: 99%

Role of counterregulatory hormones in the catabolic response to stress.

Gelfand¹,

Matthews²,

Bier³

et al. 1984

222

Abstract. Patients with major injury or illness develop protein wasting, hypermetabolism, and hyperglycemia with increased glucose flux. To assess the role of elevated counterregulatory hormones in this response, we simultaneously infused cortisol (6 mg/M2 per h), glucagon (4 ng/kg per min), epinephrine (0.6 11g/m2 per min), and norepinephrine (0.8 group as was the elevation in plasma insulin. Most plasma amino acids rose rather than fell. In both infusion protocols nitrogen wasting was accompanied by only modest increments in 3-methylhistidine excretion (-20-30%) and no significant change in leucine flux.We conclude: (a) Prolonged elevations of multiple stress hormones cause persistent hyperglycemia, increased glucose turnover, and increased nitrogen loss; (b) The sustained nitrogen loss is no greater than that produced by cortisol alone; (c) Glucagon, epinephrine, and norepinephrine transiently augment cortisol-induced nitrogen loss and persistently accentuate hyperglycemia; (d) Counterregulatory hormones contribute to, but are probably not the sole mediators of the massive nitrogen loss, muscle proteolysis, and hypermetabolism seen in some clinical settings of severe stress.

“…Although insulin influenices both protein synthesis and protein degradation in skeletal muntiscle and abnormalities of both pathways have been described in experimental diabetes mellitus, potential abnormalities of other factors regulating protein and amino acid metabolism in diabetic muscle have not been fully explored. Catecholamines acting througlh a fB-adrenergic receptor and in association with increased intracellular levels of cAMP are potent inhibitors of alanine and glutamine formation and release from skeletal muscle (17)(18)(19). Skeletal muscle of diabetic animals showed a marked loss of responsiveness to these effects of catecholamines, because 1,000-to 10,000-fold greater concentrations of epinephrine were required to alter amino acid release or lactate production with diabetic as compared with control imuscles (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Agonists that alter mtuscle cyclic nucleotide levels also provide important control mechanisms for the regulation of skeletal musele protein and amino acid metabolism. Physiologic levels of adrenergic and serotonergic agonists, acting in association with increatsed initracellulatr levels of cyclic (c)AMlP,l inhibit skeletal mutscle alanine aind gluttami ne formation and release (17)(18)(19)(20); physiologic levels of choliniergic agonists acting in association with inereased intracelltu-lar levels of cGMP, stimulate skeletal muscle alanine and glutamine formation and release (21,22). The impact of experimental, streptozotocin-induced diabetes on the actions of these agonists on skeletal muscle cyclic nucleotide metabolism and on the formation and release of alanine and glutamine has been investigated using intact rat epitrochlaris skeletal muscle preparations.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Streptozotocin-induced Diabetes Mellitus on Cyclic Nucleotide Regulation of Skeletal Muscle Amino Acid Metabolism in the Rat

Garber¹

1980

A B S T R A C T The imllpatet of clial)etes on cyclic nucleotide-associated meclhanismiis regulating skeletal muscle proteini and aminio acid metal)olism was assessed using epitrochlaris preparations fromi streptozotocin-induced diabetic rats. 1 nl epinephrine inhibited alanine and glutamine release from control preparations,lbult no inhibition wvas observed from diabetic preparations with <0.1 mM. 10 nNI epinephrinie stimulated lactate productioni from control muscle but stimulation in diabetic preparattions was observed only at 0.1 m.N Serotonin inhibited amino acid release and stimulated lactate production equallyl in control and diabetic muscle. 0.1 mMI epinephrine increased eyelic (c)AMIP levels by 360% in control muscles, but these levels were increased only 83% in diabetic muscle. Basal-, fluoride-, and serotonin-stimulated adenylvl cyclase activities were equall in membrane preparations of diabetic and control musele, but epinephrine-stimiiulated adenylyl cyclase was reduced bv 60% in diabetic muscle. Carbavmvlcholine stimulaltion of' alanine and glutatmine release wvas blunted in diabetic preparations.Carbamylcholine increased cGCMP levels in control but not in diabetic muscle. In diabetic muscle, guanylyl cyclase activity was 65% of control and the stimulation of cvclase activity by sodium azide was less in diabetic than control preparations. Added cGNIP stimulated alanine and gltatimine release from control, but not from diabetic mutscle. These data stuggest a loss of adrenergic aind cholinergic responsiveness in diabetic muscle. Becauste aimino acid release also showed a decreased responsiveness to aidded cANIP and cGMP, the presenice of other deraingements in the mechanism(s) of cyclic nucleotide regulationi of muscle aimino acid metabolism also seems likely.