INSULIN DOES NOT STIMULATE PROTEIN-SYNTHESIS ACUTELY IN PREPUBERTAL CHILDREN WITH INSULIN-DEPENDENT DIABETES-MELLITUS

Insulin treatment in adult type I diabetic patients decreases protein loss primarily by inhibiting protein breakdown without stimulating pro tein synthesis. In young growing rodents, insulin treatment has been r eported to stimulate protein synthesis. We examined whether insulin st imulates protein synthesis in normally growing prepubertal children wi th insulin-dependent diabetes mellitus. Five prepubertal children with insulin-dependent diabetes mellitus (aged 8.6-11.25 yr) were studied in the postabsorptive state on two occasions: once during insulin depr ivation (I-; blood glucose, 325 +/- 67.8 mg/dL; mean +/- SD) and once during insulin administration for 4 h (I+; blood glucose, 96 +/- 23.6 mg/dL). Leucine kinetics were measured using a 4-h primed continuous i nfusion of L-[1-C-13]leucine. Serum insulin concentrations were lower (I-vs. I+, 0.6 +/- 0.3 vs. 7.5 +/- 4.3 mu U/mL; mean +/- SD; P = 0.02) , whereas serum beta-hydroxybutyrate (I-vs. I+, 3.4 +/- 0.5 vs. 0.9 +/ - 0.5 mg/dL; P < 0.001) and free fatty acid concentrations (I-vs. 1+, 2.9 +/- 0.4 vs. 0.9 +/- 0.4 mEq/L; P < 0.001) were higher in the insul in-deprived state than during insulin administration. Leucine Ra, an i ndex of protein breakdown (I-vs. I+, 200.5 +/- 23.4 vs. 167 +/- 17 mu mol/kg; P = 0.008), and leucine oxidation (I-vs. I+, 56.5 +/- 20.7 vs. 29.6 +/- 9.3 mu mol/kg h; P = 0.03) were reduced by insulin treatment . Nonoxidative leucine disposal, an index of protein synthesis, was no t affected by insulin treatment (I-vs. I+, 144 +/- 20.8 vs. 137.5 +/- 13.5 mu mol/kg.h; P = 0.4). We conclude that the acute decline in net protein loss during insulin treatment in growing prepubertal children, like that in adults, is due primarily to an inhibition of protein bre akdown without stimulation of protein synthesis.