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1 Medicine, University of Southern California, Los Angeles, California, United States; Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States
2 Kinesiology and Biological Sciences, University of Southern California, Los Angeles, California, United States; Physical Therapy, Rehabilitation Sciences Division, University of Texas Medical Branch, Galveston, Texas, United States
3 Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas, United States
* To whom correspondence should be addressed. E-mail: evolpi{at}utmb.edu.
Insulin promotes muscle anabolism, but it is still unclear whether it stimulates muscle protein synthesis in humans. We hypothesized that insulin can increase muscle protein synthesis only if it increases muscle amino acid availability. We measured muscle protein and amino acid metabolism using stable isotope methodologies in 19 young healthy subjects at baseline and during insulin infusion in one leg at low- (LD, 0.05 mUmin-1100 ml-1), intermediate (ID, 0.15 mUmin-1100 ml-1), or high (HD, 0.30 mUmin-1100-1) doses. Insulin was infused locally to induce muscle hyperinsulinemia within the physiological range while minimizing the systemic effects. Protein and amino acid kinetics across the leg were assessed using stable isotopes of amino acids and muscle biopsies. LD did not affect amino acid delivery to the muscle (-9±18% change over baseline), muscle protein synthesis (16±26%), breakdown, or net balance. ID increased (P<0.05) amino acid delivery (+63±38%), muscle protein synthesis (+157±54%), and net protein balance, with no change in breakdown. HD did not change amino acid delivery (+12±11%) or muscle protein synthesis (+9±19%), and tended to reduce protein breakdown (-17±15%), thus improving net muscle protein balance, but to a lesser degree than ID. Changes in muscle protein synthesis were strongly correlated with changes in muscle blood flow, amino acid delivery and availability. In conclusion, physiological hyperinsulinemia promotes muscle protein synthesis as long as it concomitantly increases muscle blood flow and amino acid availability.
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