Differential Effects of Prednisone and Growth Hormone on Fuel Metabolism and Insulin Antagonism in Humans

Abstract

Human growth hormone (hGH) and prednisone cause insulin resistance and glucose intolerance. However, it is unknown whether hGH and prednisone antagonize insulin action on protein, fat, and carbohydrate metabolism by a common or independent mechanism. Therefore, protein, fat, and carbohydrate metabolism was assessed simultaneously in four groups of eight subjects each after 7 days of placebo, recombinant DNA hGH (rhGH; 0.1 mg · kg−1 · day−1), prednisone (0.8 mg · kg−1 · day−1), or rhGH and prednisone administration after an 18-h fast and during gut infusion of glucose and amino acids (fed state). Fasting plasma glucose concentrations were similar during placebo and rhGH but elevated (P < 0.001) during combined treatment, whereas plasma insulin concentrations were higher (237 ± 57 pmol/ml, P < 0.001) during combined than during placebo, rhGH, or prednisone treatment (34, 52, and 91 pM, respectively). In the fed state, plasma glucose concentrations were elevated only during combined treatment (11.3 ± 2.1 mM, P < 0.001). Plasma insulin concentrations were elevated during therapy with prednisone alone and rhGH alone (667 ± 72 and 564 ± 65 pmol/ml, respectively, P < 0.001) compared with placebo (226 ± 44 pmol/ml) but lower than with the combined rhGH and prednisone treatment (1249 ± 54 pmol/ml, P < 0.01). Protein oxidation ([14C]leucine) increased (P < 0.001) with prednisone therapy, decreased (P < 0.001) with rhGH treatment, and was normal during the combined treatment. By indirect calorimetry, glucose oxidation was similar in all groups; fasting fat oxidation was decreased by prednisone (P < 0.001) and increased by rhGH, although only significantly in the fed state (P < 0.01). In summary, insulin antagonism of rhGH and prednisone are probably caused by independent mechanisms in which rhGH and prednisone may reciprocally regulate the oxidation of protein and fat while decreasing the efficiency of glucose disposal.