EXOGENOUS INSULIN REDUCES PROTEOLYSIS AND PROTEIN-SYNTHESIS IN EXTREMELY LOW-BIRTH-WEIGHT INFANTS

Objective: To determine the effect of a continuous insulin infusion on protein and glucose metabolism in extremely low birth weight (ELBW) i nfants. Study design: We measured the rate of appearance (Ra) of the e ssential amino acids leucine and phenylalanine (reflecting proteolysis ), utilization of phenylalanine for protein synthesis, and glucose Ra using stable isotope tracers during a basal infusion of glucose (6 mg/ kg/min) and in response to a continuous infusion of insulin (0.05 U/kg /hr) by means of the euglycemic hyperinsulinemic clamp technique. Four clinically stable, euglycemic ELBW infants (26 +/- 0 weeks' gestation , 894 +/- 44 gm birth weight, 2.8 +/- 0.8 days of age) were studied. R esults: In response to a greater than tenfold increase in insulin conc entration (from 7 +/- 2 to 79 +/- 13 mu U/ml), there was a 20% decreas e in leucine Ra (Basal: 272 +/- 27 mu mol/kg/hr; Insulin: 226 +/- 29 m u mol/kg/hr; p < 0.01) and in phenylalanine Ra (Basal: 91 +/- 5 mu mol /kg/hr; Insulin: 72 +/- 2 mu mol/kg/hr; p < 0.05). Use of phenylalanin e for protein synthesis also decreased by a similar magnitude (Basal: 77 +/- 4 mu mol/kg/hr; Insulin: 62 +/- 1 mu mol/kg/hr; p < 0.05). Gluc ose utilization doubled (from 8 +/- 0.9 to 15.7 +/- 1.1 mg/kg/min; p = 0.0003) and plasma lactate concentrations tripled (from 2.1 +/- 0.5 t o 5.7 +/- 1.0 mmol/L; p < 0.05) during the insulin infusion. Conclusio ns: During an infusion of glucose alone, pharmacologic concentrations of insulin in ELBW infants produced no net protein anabolic effect. Fu rthermore, euglycemic hyperinsulinemia was accompanied by development of significant metabolic acidosis.