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.

This article has been cited by other articles:

				O. Schakman, S. Kalista, L. Bertrand, P. Lause, J. Verniers, J. M. Ketelslegers, and J. P. Thissen Role of Akt/GSK-3{beta}/{beta}-Catenin Transduction Pathway in the Muscle Anti-Atrophy Action of Insulin-Like Growth Factor-I in Glucocorticoid-Treated Rats Endocrinology, August 1, 2008; 149(8): 3900 - 3908. [Abstract] [Full Text] [PDF]

				O Schakman, H Gilson, and J P Thissen Mechanisms of glucocorticoid-induced myopathy J. Endocrinol., April 1, 2008; 197(1): 1 - 10. [Abstract] [Full Text] [PDF]

				O. Schakman, H. Gilson, V. de Coninck, P. Lause, J. Verniers, X. Havaux, J. M. Ketelslegers, and J. P. Thissen Insulin-Like Growth Factor-I Gene Transfer by Electroporation Prevents Skeletal Muscle Atrophy in Glucocorticoid-Treated Rats Endocrinology, April 1, 2005; 146(4): 1789 - 1797. [Abstract] [Full Text] [PDF]

				M. Fournier, Z.-S. Huang, H. Li, X. Da, B. Cercek, and M. I. Lewis Insulin-like growth factor I prevents corticosteroid-induced diaphragm muscle atrophy in emphysematous hamsters Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R34 - R43. [Abstract] [Full Text] [PDF]

				A. Sevette, A. J. Kee, A. R. Carlsson, R. C. Baxter, and R. C. Smith Parenteral nutrition with lipid or glucose suppresses liver growth and response to GH in adolescent male rats Am J Physiol Endocrinol Metab, November 1, 2001; 281(5): E1063 - E1072. [Abstract] [Full Text] [PDF]

				J. M. Pell, R. A. Hill, C. E. H. Stewart, C. R. Weston, and H. C. Flick-Smith Enhancement of Insulin-Like Growth Factor I Activity by Novel Antisera: Potential Structure/Function Interactions Endocrinology, February 1, 2000; 141(2): 741 - 751. [Abstract] [Full Text] [PDF]