INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I ENHANCE HUMAN SKELETAL-MUSCLE PROTEIN ANABOLISM DURING HYPERAMINOACIDEMIA BY DIFFERENT MECHANISMS

Insulin inhibits proteolysis in human muscle thereby increasing protei n anabolism, In contrast, IGF-I promotes muscle protein anabolism prin cipally by stimulating protein synthesis, As increases or decreases of plasma amino acids may affect protein turnover in muscle and also alt er the muscle's response to insulin and/or IGF-I, this study was desig ned to examine the effects of insulin and IGF-I on human muscle protei n turnover during hyperaminoacidemia. We measured phenylalanine balanc e and [H-3]phenylalanine kinetics in both forearms of 22 postabsorptiv e adults during a continuous [H-3]phenylalanine infusion. Measurements were made basally and at 3 and 6 h after beginning a systemic infusio n of a balanced amino acid mixture that raised arterial phenylalanine concentration about twofold, Throughout the 6 h, 10 subjects received insulin locally (0.035 mU/min per kg) into one brachial artery while 1 2 other subjects were given intraaterial IGF-I (100 ng/min per kg) to raise insulin or IGF-I concentrations, respectively, in the infused ar m, The contralateral arm in each study served as a simultaneous contro l for the effects of amino acids (aa) alone. Glucose uptake and lactat e release increased in the insulin- and IGF-I-infused forearms (P < 0. 01) but did not change in the contralateral (aa alone) forearm in eith er study, In the aa alone arm in both studies, hyperaminoacidemia reve rsed the postabsorptive net phenylalanine release by muscle to a net u ptake (P < 0.025, for each) due to a stimulation of muscle protein syn thesis, In the hormone-infused arms, the addition of either insulin or IGF-I promoted greater positive shifts in phenylalanine balance than the aa alone arm (P < 0.01), With insulin, the enhanced anabolism was due to inhibition of protein degradation (P < 0.02), whereas IGF-I aug mented anabolism by a further stimulation of protein synthesis above a a alone (P < 0.02), We conclude that: (a) hyperaminoacidemia specifica lly stimulates muscle protein synthesis; (6) insulin, even with hypera minoacidemia, improves muscle protein balance solely by inhibiting pro teolysis; and (c) hyperaminoacidemia combined with IGF-I enhances prot ein synthesis more than either alone.