The anti-catabolic efficacy of insulin-like growth factor-I is enhanced by its early administration to rats receiving dexamethasone.
The anti-catabolic efficacy of IGF-I treatment commencing before, with or after the onset of catabolism was compared in order to test whether earlier treatment can more effectively blunt a catabolic response. Young rapidly growing male rats (145 g body weight) and old weight-stable female rats (270 g body weight) were used in two experiments. The IGF-I variant LR 3IGF-I was continuously infused at 280 micrograms/day from 2 days before (early), concurrent with or 2 days after (delayed) commencement of a 6 day dexamethasone infusion (125 micrograms/kg per day). Both early and delayed treatment of young rats with LR 3IGF-I significantly reduced the measured catabolic effects of dexamethasone. Early treatment was more effective than delayed treatment, with significantly higher nitrogen balance (90 +/- 12 vs 31 +/- 6 mg/day), carcass nitrogen gain (0.37 +/- 0.27 vs -1.13 +/- 0.10% per day) and protein fractional synthesis rates after 2 (10.4 +/- 0.5 vs 8.3 +/- 0.2% per day) and 6 days of dexamethasone (8.2 +/- 0.6 vs 7.0 +/- 0.3% per day). Similarly, fractional breakdown rates of carcass protein were maintained at significantly lower levels in rats given early treatment (6.23 +/- 0.24 vs 6.60 +/- 0.22% per day). In contrast, the old rats were less responsive to LR 3IGF-I treatment and only early and concurrent treatment significantly reduced the catabolic response, partly because of higher food intake. Early treatment was superior to delayed treatment and led to significantly higher nitrogen balance(-19 +/- 11 vs -83 +/- 7 mg/day) and carcass nitrogen fractional gain (-1.19 +/- 0.40 vs -2.76 +/- 0.37% per day) as well as lower final rates of carcass protein fractional breakdown (3.55 +/- 0.15 vs 3.83 +/- 0.07% per day). These experiments show that early (prophylactic) treatment with IGF-I is superior to delayed treatment for reducing catabolism induced by dexamethasone. The results provide the basis for further research to determine if prophylactic IGF-I treatment is useful in other circumstances where catabolism can be anticipated, such as in elective major surgery.
Tomas
F M
FM
Cooperative Research Centre for Tissue Growth and Repair, Adelaide, South Australia, Australia.
D000375:Aging / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006128:Growth / Q000187:drug effects*; D006133:Growth Substances / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D012044:Regression Analysis; D013997:Time Factors
D006133:Growth Substances; C084339:LR(3)IGF-I; D009124:Muscle Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D009584:Nitrogen