Y. Sakurai et al., STIMULATION OF MUSCLE PROTEIN-SYNTHESIS BY LONG-TERM INSULIN INFUSIONIN SEVERELY BURNED PATIENTS, Annals of surgery, 222(3), 1995, pp. 283-297
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.