Acute hyperaminoacidemia does not suppress insulin-mediated glucose turnover in healthy young men.

Elevated circulating amino acids (AA) concentrations are purported to cause insulin resistance (IR) in humans. To quantify hyperaminoacidemia effects on insulin-mediated glucose turnover in healthy men, we performed 2-stage pancreatic clamps using octreotide with glucagon and growth hormone replacement. In the basal stage, insulin was infused to maintain euglycemia at postabsorptive levels. During the clamp stage, insulin was raised to postprandial levels, glycemia clamped at 5.5 mmol/L by glucose infusion, and branched-chain AA (BCAA) maintained at either postabsorptive (Hyper1;  = 8) or postprandial (Hyper2;  = 7) by AA infusion. Glucose turnover was measured by d-3-[H]glucose dilution. Octreotide suppressed C-peptide; glucagon, growth hormone, and glycemia were maintained at postabsorptive levels throughout. Insulin did not differ at postabsorptive (72 ± 5 vs. 60 ± 5 pmol/L; Hyper1 vs. Hyper2) and increased to similar concentrations at basal (108 ± 11 vs. 106 ± 14) and clamp stages (551 ± 23 vs. 540 ± 25). Postabsorptive BCAA were maintained during Hyper1 and increased >2-fold (830 ± 26 µmol/L) during Hyper2. Endogenous glucose production was similarly suppressed (0.95 ± 0.16 vs. 1.37 ± 0.23 mg/kg lean body mass/min; Hyper1 vs. Hyper2) and basal glucose disposal (3.44 ± 0.12 vs. 3.67 ± 0.14) increased to similar levels (10.89 ± 0.56 vs. 11.11 ± 1.00) during the clamp. Thus, acute physiological elevation of AA for 3 h did not cause IR in healthy men. A 2-step pancreatic clamp was used to quantify the effect of AA on insulin sensitivity in humans. Acute physiological elevation of circulating AA to postprandial levels does not cause IR in healthy men.