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 p henylalanine (Phe) balances, as well as estimates of protein degradati on (Phe R(a)) and synthesis (Phe R(d)) were measured before and at 3 a nd 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 I GF-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 gluc ose uptake was observed at the lowest dose, whereas four- to sixfold i ncreases were observed at both the 6 and 10 mu g.kg(-1) h(-1) doses (b oth P < 0.02). Forearm Phe balance shifted positively at all three dos es by 27 +/- 6, 48 +/- 7, and 51 +/- 9 nmol.min(-1).100 ml(-1), respec tively (all P < 0.01). At all three doses, Phe R(d) increasedcomparabl y 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). Forea rm muscle metabolism was also studied in the contralateral non-IGF-inf used 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) dos e), contralateral forearm muscle glucose, lactate, or Phe handling did not change. In conclusion, intra-arterial IGF-I exhibits growth hormo ne-like effects at all doses tested, whereas the insulinlike effects a re observed at higher doses; these effects appear dependent on the rou te of administration.