Influence of glucocorticoids on skeletal muscle proteolysis in normal and diabetic-adrenalectomized eviscerated rats.
The effect on skeletal muscle proteolysis of acute (20-hour) glucocorticoid treatment (dexamethasone 1.5 mg/kg, subcutaneously [SC]) was tested using the eviscerated rat preparation. According to this method, the peripheral tissues (primarily the skeletal muscles) are isolated by functional hepatectomy-nephrectomy. Total proteolysis is estimated from the rate of rise of plasma tyrosine concentration in the presence of cycloheximide to block protein synthesis. Myofibrillar proteolysis is measured from the rate of release into the plasma of the nonreutilized, nonmetabolized amino acid 3-methylhistidine (3MH), in the absence of cycloheximide. In normal rats, dexamethasone increased total proteolysis by 20% and myofibrillar proteolysis by 75% (both P less than .025 v saline controls). In diabetic-adrenalectomized rats prepared 2 weeks earlier (65 mg/kg streptozocin [STZ] followed by adrenalectomy), dexamethasone caused much greater increments in rates of total proteolysis (94%) and myofibrillar proteolysis (240%) (both P less than .001 v saline controls). Because diabetic animals are extremely sensitive to glucocorticoid-induced proteolysis, we also examined whether the acute proteolytic effect of diabetes itself might be mediated by adrenal cortical hormones. Previously adrenalectomized rats studied 20 hours after STZ showed a 40% augmentation of total proteolysis (P less than .01), an effect similar to that produced by acute diabetes in rats with intact adrenals. We conclude that glucocortical hormones cause a catabolic effect on total and myofibrillar skeletal muscle protein which is exaggerated when the counteracting action of insulin is reduced, but that the excess proteolysis of acute insulin deficiency is independent of the endogenous glucocorticoids secretion.
John B. Pierce Foundation Laboratory, New Haven, CT 06519.
O L
OL
Smith
C Y
CY
Wong
R A
RA
Gelfand
D000315:Adrenalectomy; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006652:Histological Techniques; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014781:Viscera
D005938:Glucocorticoids; D010447:Peptide Hydrolases