Use of a leucine clamp to demonstrate that IGF-I actively stimulates protein synthesis in normal humans

Abstract

Insulin-like growth factor I (IGF-I) is thought to mediate the anabolic action of growth hormone. A glucose and amino acid clamp technique was used to investigate the effects of a 3-h intravenous infusion of either 43.7 pmol.kg-1.min-1 (20 micrograms.kg-1.h-1) IGF-I or 3.4 pmol.kg-1.min-1 (0.5 mU.kg-1.min-1) insulin on whole body leucine turnover in five normal human volunteers. During the IGF-I infusion, IGF-I levels increased (P < 0.01; 26.6 +/- 2.8 to 88.9 +/- 14.2 nmol/l) and insulin levels fell (P < 0.05; 0.096 +/- 0.018 to 0.043 +/- 0.009 nmol/l). During the insulin infusion, insulin levels increased (P < 0.01; 0.057 +/- 0.013 to 0.340 +/- 0.099 nmol/l), and there was no change in IGF-I. There was no significant change in leucine production rate (Ra; a measure of protein degradation) during the IGF-I infusion (2.23 +/- 0.17 to 2.13 +/- 0.2 mumol.kg-1.min-1), but there was an increase (P < 0.03) in nonoxidative leucine disposal rate (Rd; a measure of protein synthesis; 1.83 +/- 0.15 to 2.05 +/- 0.21 mumol.kg-1.min-1). In contrast, insulin reduced (P < 0.02) leucine Ra (1.81 +/- 0.24 to 1.47 +/- 0.24 mumol.kg-1.min-1) and had no effect on nonoxidative leucine Rd (1.44 +/- 0.25 to 1.41 +/- 0.22 mumol.kg-1.min-1). We conclude that IGF-I, under conditions of adequate substrate supply, directly increases protein synthesis in contrast to insulin, which exerts its anabolic action by reducing proteolysis.

A comparison of changes in whole body and skin amino acid metabolism of sheep in response to 24 h continuous infusions of variants of insulin-like growth factor 1

“…In general, administration in man or sheep of either rhIGF-1 (Clemmons et al 1992;Cottam et al 1992;Turkalj et al 1992;Elahi et al 1993;Russell-Jones et al 1994;Fryburg et al 1995;Oddy and Owens 1996) or LR 3 IGF-1 (Hocking Edwards et al 1994) provokes a rapid decline in plasma insulin, as was observed in the current study. Although the inter-animal variability was high, there was a trend for insulin concentrations to decline more following a 24-h infusion of LR 3 -IGF-1.…”

“…unbound to any of the IGFBPs. The LR 3 IGF-1 binds very poorly to IGFBP compared with endogenous or rhIGF-1; this results in greater potential biological activity and yields whole body responses Hocking Edwards et al 1994) at lower doses than used in trials using rhIGF-1 (Clemmons et al 1992;Turkalj et al 1992;Elahi et al 1993;Russell-Jones et al 1994). Despite this inherent difference in biological activity between rhIGF-1 and LR 3 IGF-1, it was decided to use similar doses of each, but at quantities known to yield responses with the native form (i.e.…”

The metabolic role of growth hormone in humans with particular reference to fasting

“…In contrast, there is a lack of stimulation of wholebody protein synthesis with systemic infusion of IGF-I [271], which probably results from the fall in circulating insulin and/or amino acid concentrations that accompanies systemic IGF-I infusion in vivo. When amino acids [272] or insulin [273] is co-administered, IGF-I clearly stimulates whole-body protein synthesis.…”

IGF-I abuse in sport: Current knowledge and future prospects for detection

“…rhIGF-I infusion has been shown to combine the insulin-like property of inhibiting proteolysis [13,14] with the GH-like property of stimulating protein synthesis [15]. The intracellular signalling mechanisms of IGF-I are not fully understood but it is likely that IGF-I acts, at least in part, by stimulating amino acid uptake into cells [16].…”