TY - JOUR
T1 - The effect of systemic hyperinsulinemia with concomitant amino acid infusion on skeletal muscle protein turnover in the human forearm
AU - Newman, Elliot
AU - Heslin, Martin J.
AU - Wolf, Ronald F.
AU - Pisters, Peter W.T.
AU - Brennan, Murray F.
N1 - Funding Information:
From the Surgical Metabolism Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY. Submitted October 2,1992; accepted February 11, 1993. Supported by the Surgical Metabolism Fund and US Fublic Health Sentice Grant No. T32 CA 09501. Presented in part at The American Sociev for Clinical Investigation National Meeting, Seattle, WA, May 1991, andpreviously published in abstract form (Clin Res 39:384a). Address reprint requests to Muway F. Brennan, MD, Chairman, Depatiment of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 YorkAve, New York, NY10021. Copyright 0 1994 by W.B. Saunders Company 0026-0495/9414301-0011$03.0010
PY - 1994/1
Y1 - 1994/1
N2 - In vitro, insulin has been shown to increase skeletal muscle (SM) protein synthesis and decrease SM protein breakdown. Whether these same effects are found in vivo in man is less clear. The study of the effect of hyperinsulinemia (INS) on SM protein turnover (SMPT) is complicated by hypoaminoacidemia, which can obviate the true effect of insulin on SMPT. To prevent this, we studied the effect of INS on SMPT in the human forearm with amino acid (AA) infusion to ensure adequate substrate for full evaluation of insulin's effect. Twelve healthy volunteers (aged 53 ± 3 years) were studied. Steady-state AA kinetics were measured across the foream after a systemic 2-hour primed continuous infusion of 3H-phenylalanine (3H-Phe) and 14C-leucine (14C-Leu) in the postabsorptive (PA) state and in response to systemic INS (71 ± 5 μU/mL). AAs were infused during INS as 10% Travasol (Travenol Laboratories, Deerfield, IL) at .011 mL/kg/min to maintain PA branched-chain AA (BCAA) levels, known regulators of SMPT, and to mildly elevate total AA levels. The negative PA net balance of both Phe and total Leu carbons (LeuC) became positive with INS + AA infusion (Phe from -16 ± 2 to 12 ± 3 nmol/min 100 g [P < .01]; LeuC from -26 ± 6 to 24 ± 7 nmol/min 100 g [P < .01]). The rate of disposal (Rd) of Phe into SM, an index of protein synthesis, increased from 31 ± 5 nmol/min 100 g postabsorptively to 52 ± 7 nmol/min 100 g with INS + AA (P < .01), while the LeuC Rd increased from 82 ± 16 to 86 ± 18 nmol/min 100 g (P = .85). The rate of appearance (Ra) of phe from SM, an index of protein breakdown, decreased from 48 ± 6 nmol/min 100 g postabsorptively to 40 ± 5 nmol/min 100 g with INS + AA (P = .06), while the LeuC Ra decreased from 107 ± 18 to 62 ± 14 nmol/min 100 g (P < .03). These data suggest that the anabolic effect of insulin across the human forearm, in the presence of mildly elevated arterial AA levels, is to increase SM protein synthesis and decrease SM protein breakdown.
AB - In vitro, insulin has been shown to increase skeletal muscle (SM) protein synthesis and decrease SM protein breakdown. Whether these same effects are found in vivo in man is less clear. The study of the effect of hyperinsulinemia (INS) on SM protein turnover (SMPT) is complicated by hypoaminoacidemia, which can obviate the true effect of insulin on SMPT. To prevent this, we studied the effect of INS on SMPT in the human forearm with amino acid (AA) infusion to ensure adequate substrate for full evaluation of insulin's effect. Twelve healthy volunteers (aged 53 ± 3 years) were studied. Steady-state AA kinetics were measured across the foream after a systemic 2-hour primed continuous infusion of 3H-phenylalanine (3H-Phe) and 14C-leucine (14C-Leu) in the postabsorptive (PA) state and in response to systemic INS (71 ± 5 μU/mL). AAs were infused during INS as 10% Travasol (Travenol Laboratories, Deerfield, IL) at .011 mL/kg/min to maintain PA branched-chain AA (BCAA) levels, known regulators of SMPT, and to mildly elevate total AA levels. The negative PA net balance of both Phe and total Leu carbons (LeuC) became positive with INS + AA infusion (Phe from -16 ± 2 to 12 ± 3 nmol/min 100 g [P < .01]; LeuC from -26 ± 6 to 24 ± 7 nmol/min 100 g [P < .01]). The rate of disposal (Rd) of Phe into SM, an index of protein synthesis, increased from 31 ± 5 nmol/min 100 g postabsorptively to 52 ± 7 nmol/min 100 g with INS + AA (P < .01), while the LeuC Rd increased from 82 ± 16 to 86 ± 18 nmol/min 100 g (P = .85). The rate of appearance (Ra) of phe from SM, an index of protein breakdown, decreased from 48 ± 6 nmol/min 100 g postabsorptively to 40 ± 5 nmol/min 100 g with INS + AA (P = .06), while the LeuC Ra decreased from 107 ± 18 to 62 ± 14 nmol/min 100 g (P < .03). These data suggest that the anabolic effect of insulin across the human forearm, in the presence of mildly elevated arterial AA levels, is to increase SM protein synthesis and decrease SM protein breakdown.
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U2 - 10.1016/0026-0495(94)90159-7
DO - 10.1016/0026-0495(94)90159-7
M3 - Article
C2 - 8289678
AN - SCOPUS:0028140388
SN - 0026-0495
VL - 43
SP - 70
EP - 78
JO - Metabolism
JF - Metabolism
IS - 1
ER -