EFFECTS OF GROWTH-HORMONE AND IGF-I ON GLUCOCORTICOID-INDUCED PROTEINCATABOLISM IN HUMANS

The effects of similar increases in total insulinlike growth factor I (IGF-I) plasma concentrations achieved by either recombinant human (rh ) growth hormone (GH) or rhIGF-I administration on whole body protein and glucose kinetics were assessed. Twenty-six healthy subjects receiv ed methylprednisolone (0.5 mg . kg(-1). day(-1) orally) during 6 days in combination with either placebo (saline sc), GH (0.3 mg . kg(-1). d ay(-1) sc), or ICF-I (80 mu g . kg(-1). day(-1) sc) in a double-blind randomized fashion. Glucocorticoid administration resulted in protein catabolism as indicated by an increase in leucine flux and a 62 +/- 13 % increase in leucine oxidation ([1-C-13]leucine infusion technique); this increase was abolished by GH (-1 +/- 18%) and was statistically i nsignificant during IGF-I treatment (+53 +/- 25%). GH increased endoge nous glucose production by 28 +/- 8%, augmented glucocorticoid-induced insulin resistance of peripheral glucose clearance (euglycemic clamp) , and increased circulating lipids. IGF-I administration resulted in b oth increased endogenous glucose production and increased peripheral g lucose clearance such that plasma glucose concentrations remained unch anged. Glucocorticoid-induced insulin resistance of glucose clearance was unchanged by IGF-I. IGF-I lowered circulating GH and insulin and a ltered IGF binding proteins, which all may have reduced bioactivity of IGF-I. The data demonstrate that, in spite of similar total IGF-I pla sma concentrations during treatment, GH and IGF-I exert markedly diffe rent effects on whole body leucine, glucose, and lipid metabolism.