INSULIN-LIKE GROWTH-FACTOR-I EXERTS GROWTH HORMONE-LIKE AND INSULIN-LIKE ACTIONS ON HUMAN MUSCLE PROTEIN-METABOLISM

The effect of a 6-h intra-arterial infusion of recombinant human (rh) insulin-like growth factor I (IGF-I) on forearm muscle metabolism was studied in 19 postabsorptive subjects. Forearm glucose, lactate, and phenylalanine (Phe) balances, as well as estimates of protein degradation (Phe R(a)) and synthesis (Phe R(d)) were measured before and at 3 and 6 h into an infusion of rhIGF-I at a dose of 1.8 (n = 6), 6.0 (n = 8), or 10.0 (n = 5) mu g.kg(-1) h(-1). In response to intra-arterial IGF-I, deep venous IGF-I rose by 55, 141, and 315%, respectively (all P < 0.01), and forearm blood flow accelerated by 75 (1.8 mu g), 213 (6.0 mu g), and 159% (10.0 mu g; all P < 0.02). No change in forearm glucose uptake was observed at the lowest dose, whereas four- to sixfold increases were observed at both the 6 and 10 mu g.kg(-1) h(-1) doses (both P < 0.02). Forearm Phe balance shifted positively at all three doses by 27 +/- 6, 48 +/- 7, and 51 +/- 9 nmol.min(-1).100 ml(-1), respectively (all P < 0.01). At all three doses, Phe R(d) increasedcomparably by 49-74% (all P <0.05) At the 6.0 and 10.0 but not the 1.8 mu g kg(-1).h(-1) dose, Phe R(a) decreased by similar to 45% (P < 0.02). Forearm muscle metabolism was also studied in the contralateral non-IGF-infused arm at these three doses. Despite increases in deep venous IGF-I up to 517 ng/ml due to recirculating IGF-I (10.0 mu g.kg(-1) h(-1) dose), contralateral forearm muscle glucose, lactate, or Phe handling did not change. In conclusion, intra-arterial IGF-I exhibits growth hormone-like effects at all doses tested, whereas the insulinlike effects are observed at higher doses; these effects appear dependent on the route of administration.