Skeletal muscle proteolysis in rats with acute streptozocin-induced diabetes.
Skeletal muscle proteolysis was studied in rats 1 day after induction of diabetes with 65 mg/kg streptozocin. An evisceration procedure, including functional hepatectomy-nephrectomy, was performed, and the rate of proteolysis in the remaining tissues, primarily skeletal muscles, was evaluated over 2 h. With cycloheximide to block protein synthesis, total protein breakdown was measured from the rate of rise in plasma tyrosine concentration. The rate of degradation of contractile (myofibrillar) protein was estimated from the rate of rise in plasma concentration of 3-methylhistidine released from the breakdown of actomyosin. Compared with nondiabetic control preparations, the total protein degradation rate was increased 30% by diabetes (P less than .001), and myofibrillar catabolism was accelerated by 60% (P less than .005). In diabetes, the increase in proteolysis was accompanied by reductions in circulating insulin to 25-50% of normal level, whereas food intake did not differ from control. Treatment of diabetic rats with exogenous insulin, including acute infusions postoperatively, completely reversed the proteolytic effects of diabetes. The findings demonstrate that the hypoinsulinemia of acute diabetes increases the catabolism of skeletal muscle protein and that the inhibitory effect of normal levels of insulin includes a specific action to restrain myofibrillar proteolysis.
Smith
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John B. Pierce Foundation Laboratory, Yale University School of Medicine, New Haven, Connecticut 06519.
Wong
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Gelfand
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D000208:Acute Disease; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003345:Corticosterone / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D007328:Insulin / Q000097:blood; D008297:Male; D008762:Methylhistidines / Q000097:blood; D009124:Muscle Proteins / Q000378:metabolism; D009132:Muscles / Q000201:enzymology*; D009210:Myofibrils / Q000201:enzymology; D010447:Peptide Hydrolases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014443:Tyrosine / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D008762:Methylhistidines; D009124:Muscle Proteins; D014443:Tyrosine; D010447:Peptide Hydrolases; C028118:3-methylhistidine; D003345:Corticosterone