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Effects of Insulin-Like Growth Factor I Combined with Growth Hormone on Glucocorticoid-Induced Whole-Body Protein Catabolism in Man¹

Departments of Research and of Internal Medicine (K.B., R.N., U.K.), University Hospital Basel, 4031 Basel; Endocrinological Practice (J.G.), 4052 Basel; and Division of Nephrology (B.M.F.), Department of Medicine, University Hospital Bern, 3010 Bern, Switzerland

Address all correspondence and requests for reprints to: Ulrich Keller, M.D., Departments of Research and Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.

Treatment with insulin-like growth factor I (IGF-I) alone failed to affect glucocorticoid-induced protein catabolism in a previous study from our laboratory. To assess the effects of the combination of IGF-I and GH in a similar protocol, 24 normal subjects received (in a double-blind, randomized, placebo-controlled manner) sc injections of either GH alone (0.3 IU/kg·day), the combination of IGF-I (80 µg/kg·day) and GH (0.3 IU/kg·day), or placebo for a period of 6 days during which they were treated with methylprednisolone (0.5 mg/kg·day). Whole-body protein kinetics measured, using the [1-¹³C]-leucine infusion technique, demonstrated that leucine flux (a parameter of protein breakdown) increased during administration of glucocorticoids alone (placebo group) and during GH-treatment, whereas the glucocorticoid-induced increase was abolished during IGF-I plus GH (P < 0.03 vs. GH). Leucine oxidation (a parameter of irreversible protein catabolism) increased in the placebo group (+60 ± 14.5%, P < 0.005, day 7 vs. day 1), remained unchanged in the GH group (+2.5 ± 10%), and decreased in the combination group (-17.7 ± 3.3%, P < 0.002, day 7 vs. day 1). Glucose MCR decreased in the group receiving placebo (P < 0.05) and remained unchanged during combined treatment with IGF-I plus GH. It is concluded that glucocorticoid-induced protein catabolism (leucine oxidation) is abolished during coadministration of GH (anticatabolic effect), whereas treatment with IGF-I and GH results in a net anabolic effect without adverse effects on peripheral glucose clearance.

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