Insulin-like growth factor-I
insulin-like growth factor binding proteins
Springer Online Journal Archives 1860-2000
Summary We have investigated the relationship between the plasma distribution of infused recominant insulin-like growth factor-I across the insulin-like growth factor binding proteins and the resultant effects on glucose and fat metabolism. The studies were performed in 24-h fasted ram lambs which received primed constant infusions of 3H labelled glucose tracer. When isotopic equilibrium had been reached, the animals received 90-min infusions of human insulin-like growth factor-I at various doses (2.5, 20, 40 and 120 μg· kg−1·h−1, n=3 for each dose). Total plasma insulin-like growth factor-I was significantly elevated by infusion at a rate of 40 μg·kg−1·h−1 (from 185±14 μg/l to 442±41 μg/l, p〈0.05) and 120μg·kg−1h−1 (from 181±2 μg/l to 953±39 μg/1, p〈0.005). The plasma concentrations of insulin-like growth factor-I not associated with binding proteins remained undetectable (〈15 μg/l) at the end of the 2.5 and 20 μg·kg−1·h−1 doses, but were significantly elevated at the end of the 40 and 120 μg·kg−1·h−1 infusions (to 71±14 μg/l, p〈0.05 and 176±55 μg/l, p〈0.01 respectively). The infused insulin-like growth factor-I associated primarily with 35–60 kilodalton binding proteins. Glucose kinetics were significantly altered only by the highest dose infusion, during which there was a fall in plasma glucose concentration from 3.5±0.2 mmol/l to 1.9±0.2 mmol/l (p〈0.05). This was due to a 51% increase in the rate of glucose clearance. There was no significant change in the rate of glucose production. The plasma concentrations of glycerol and non-esterified fatty acid were not changed by any of the doses infused. We conclude that the hypoglycaemic action of infused recombinant insulin-like growth factor-I relates to a marked elevation of free insulin-like growth factor-I in the plasma, but that a threshold concentration of free insulin-like growth factor-I must be exceeded before this action is observed. The hypoglycaemic action of recominant insulin-like growth factor-I results primarily from an increase in glucose clearance while glucose metabolism was more sensitive than fat metabolism to infused recominant insulin-like growth factor-I. Both these actions contrast with those of insulin, and suggest that the acute metabolic effects of recombinant insulin-like growth factor-I are not mediated simply by cross-reaction with insulin receptors.
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