STIMULATION OF MUSCLE PROTEIN-SYNTHESIS BY LONG-TERM INSULIN INFUSIONIN SEVERELY BURNED PATIENTS

Objective To determine if long-term (7 days) infusion of insulin can a meliorate altered protein kinetics in skeletal muscle of severely burn ed patients and to investigate the hypothesis that changes in protein kinetics during insulin infusion are associated with an increased rate of transmembrane amino acid transport from plasma into the intracellu lar free amino acid pool. Summary Background Data In critically ill pa tients, vigorous nutritional support alone may often fail to entirely curtail muscle catabolism; insulin stimulates muscle protein synthesis in normal volunteers. Methods Nine patients with severe burns were st udied once during enteral feeding alone (control period), and once aft er 7 days of high-dose insulin. The order of treatment with insulin wa s randomized. Data were derived from a model based on a primed-continu ous infusion of L-[N-15]phenylalanine, sampling of blood from the femo ral artery and vein, and biopsies of the vastus lateralis muscle. Resu lts Net leg muscle protein balance was significantly (p < 0.05) negati ve during the control period. Exogenous insulin eliminated this negati ve balance by stimulating protein synthesis approximately 350% (p < 0. 01). This was made possible in part by a sixfold increase in the inwar d transport of amino acids from blood (p < 0.01). There was also a sig nificant increase in leg muscle protein breakdown. The new rates of sy nthesis, breakdown, and inward transport during insulin were in balanc e, such that there was no difference in the intracellular phenylalanin e concentration from the control period. The fractional synthetic rate of protein in the wound was also stimulated by insulin by approximate ly 50%, but the response was variable and did not reach significance. Conclusions Exogenous insulin may be useful in promoting muscle protei n synthesis in severely catabolic patients.