Exogenous insulin infusions are increasingly being used in ELBW infants to promote euglycemia and growth. We previously have shown that ELBW infants suppress glucose production and increase glucose utilization in response to increased glucose infusion (with a concomitant threefold increase in endogenous insulin to ≈13μU/ml), but are unable to suppress proteolysis(JCI 92:1752-8, 1993). Therefore, we hypothesized that at higher insulin levels achieved by an exogenous infusion, ELBW infants would continue to be resistant to suppression of proteolysis, yet would increase glucose utilization and suppress endogenous glucose production. To assess this, we measured the rate of appearance (Ra) of the essential amino acids leucine(LEU) and phenylalanine (PHE) (reflecting proteolysis), PHE utilization for protein synthesis (PS), and glucose Ra using stable isotope tracers during a basal infusion of glucose (6mg/kg/min) and in response to a continuous infusion of insulin (0.05U/kg/hr) using a euglycemic hyperinsulinemic clamp technique. Four euglycemic infants (26±0 wks gestation, 894±88 gms birth wt, 2.8±1.5 days of age) were studied. Results(Mean±SD; insulin in μU/ml; LEU Ra, PHE Ra, and PHE PS inμmol/kg/hr; GLU Util and GLU Ra in mg/kg/min; lactate in mmol/L;*p<0.05) Conclusions: In response to a greater than tenfold increase in insulin concentration: 1) Proteolysis was suppressed by 20%; however, utilization of PHE for protein synthesis also decreased by a similar magnitude. 2) Endogenous glucose production was not detected in any patient. 3) Glucose utilization doubled. 4) Routine use of exogenous insulin in this population must be approached with caution as serum lactate concentrations increased nearly threefold during the study. Table