Insulin-like growth factor I exerts growth hormone- 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 Ra) and synthesis (Phe Rd) 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) micrograms.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 microgram), 213 (6.0 micrograms), and 159% (10.0 micrograms; 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 micrograms.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 x 100 ml-1, respectively (all P < 0.01). At all three doses, Phe Rd increased comparably by 49-74% (all P < 0.05). At the 6.0 and 10.0 but not the 1.8 microgram.kg-1.h-1 dose, Phe Ra decreased by approximately 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 micrograms.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 insulin-like effects are observed at higher doses; these effects appear dependent on the route of administration.
Fryburg
D A
DA
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005542:Forearm / Q000098:blood supply; D013006:Growth Hormone / Q000494:pharmacology*; D006706:Homeostasis; D006728:Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D010649:Phenylalanine / Q000097:blood / Q000378:metabolism; D011994:Recombinant Proteins; D012039:Regional Blood Flow
D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D007773:Lactates; D009124:Muscle Proteins; D011994:Recombinant Proteins; D019344:Lactic Acid; D010649:Phenylalanine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone