Comparison of the effects of growth hormone and insulin-like growth factor I on substrate oxidation and on insulin sensitivity in growth hormone-deficient humans

Insulin-like growth factor-I (IGF-I) is considered to be the mediator of the growth-promoting effects of growth hor-mone (GH). The metabolic effects of these two hormones, however, are different. Whereas GH treatment leads to ele-vated insulin and glucose levels, reduced insulin sensitivity, and impaired glucose tolerance, IGF-I treatment leads to reduced insulin and GH levels and enhanced insulin sensitiv-ity. IGF-I may, therefore, not only be the mediator of the growth-promoting effects of GH but also a modulator of the effects of GH on insulin action and glucose metabolism. To study the influence of GH and IGF-I on substrate metabo-lism and insulin sensitivity (assessed by euglycemic, hyper-insulinemic clamping combined with indirect calorimetry and glucose tracer infusion), we have treated eight GH-deficient adults with GH (2 IU/m2 daily subcutaneously [s.c.]), IGF-I (10 jtg/kg h s.c.), or both hormones together for 7 d, respectively, and compared the effects of these treat-ment regimens with a control phase. Our findings suggest that (a) both GH and IGF-I promote lipolysis and lipid oxidation, albeit by different mechanisms; (b) treatment with either hormone is followed by enhanced energy expen-diture and reduced protein oxidation; and (c) IGF-I re-verses the insulin resistance induced by GH. (J. Clin. Invest. 1994.94:1126-1133.) Key words: substrate oxidation * insu-lin sensitivity * euglycemic clamp- lipolysis * energy expen-ditur