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Am J Physiol Endocrinol Metab (December 9, 2003). doi:10.1152/ajpendo.00258.2003
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Submitted on June 10, 2003
Accepted on December 4, 2003

EXTREMITY HYPERINSULINEMIA STIMULATES MUSCLE PROTEIN SYNTHESIS IN SEVERELY INJURED PATIENTS

Dennis C. Gore1*, Steven E. Wolf1, Arthur P. Sanford1, David N. Herndon1, and Robert R. Wolfe1

1 Department of Surgery, The University of Texas Medical Branch, Galveston, Texas, USA

* To whom correspondence should be addressed. E-mail: dcgore{at}utmb.edu.

Insulin has a well-recognized anabolic effect on muscle protein, yet critically ill, severely injured patients are often considered "resistant" to the action of insulin. The purpose of this study was to assess the in vivo effects of hyperinsulinemia on human skeletal muscle in severely injured patients. To accomplish this goal, 14 patients with burns encompassing over 40% of their body surface area underwent metabolic evaluation utilizing isotopic dilution of phenylalanine, femoral artery and vein blood sampling, and sequential muscle biopsies of the leg. Following baseline metabolic measurements, insulin was then infused into the femoral artery at 0.45 mIU/min/100 ml leg volume to create a local hyperinsulinemia yet with minimal systemic perturbations. Insulin administration increased femoral venous concentration of insulin (p<0.01) yet with only a 4% (insignificant) decrease in the arterial glucose concentration and a 7% (insignificant) decrease in the arterial concentration of phenylalanine. Extremity hyperinsulinemia significantly increased leg blood flow (p<0.05) and the rate of muscle protein synthesis (p<0.05). Neither the rate of muscle protein breakdown nor the rate of transmembrane transport of phenylalanine was significantly altered with extremity hyperinsulinemia. In conclusion, this study demonstrates that insulin directly stimulates muscle protein synthesis in severely injured patients.




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