Interactive effects of insulin and corticosterone on myofibrillar protein turnover in rats as determined by N tau-methylhistidine excretion.
The effects of graded doses of insulin and corticosterone on myofibrillar protein turnover were investigated in growing diabetic rats in order to assess their counteractive roles in the control of protein accretion. N tau-Methylhistidine excretion and carcass protein accretion were measured over 6 days in streptozotocin-diabetic rats receiving either a constant catabolic dose of corticosterone accompanied by graded doses of insulin or a constant dose of insulin accompanied by graded doses of corticosterone. The high corticosterone dose decreased the rate of protein accretion by both increasing the rate of degradation and decreasing the rate of synthesis. Increasing insulin dosage counteracted these effects, but could not restore positive accretion rates. Direct measurement of protein-synthesis rates gave results comparable with those obtained from use of N tau-methylhistidine excretion. At constant insulin dosage, increased corticosterone to 45 mg/kg body wt. per day caused a dose-related linear decrease in protein accretion rates from +4.5 to -3.2% per day. Growth ceased at 28 mg of corticosterone/kg body wt. per day, largely owing to a fall in synthesis rates (-3.5%/day) rather than the increase in degradation rates (+1.0%/day). However, at steroid doses greater than 30 mg/kg body wt. per day the degradation rate increased markedly and accounted for most of the additional fall in accretion. These results show that insulin antagonizes the action of glucocorticoids on both the synthesis and degradative pathways of myofibrillar protein turnover. The changes in fractional degradation rates appear relatively more attenuated by insulin than are those of synthesis.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004347:Drug Interactions; D006639:Histidine / Q000031:analogs & derivatives*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008762:Methylhistidines / Q000652:urine*; D009124:Muscle Proteins / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D051381:Rats; D014508:Urea / Q000652:urine
D001786:Blood Glucose; D007328:Insulin; D008762:Methylhistidines; D009124:Muscle Proteins; D006639:Histidine; D014508:Urea; C028118:3-methylhistidine; D003345:Corticosterone