PHYSIOLOGICAL INCREMENTS IN PLASMA-INSULIN CONCENTRATIONS HAVE SELECTIVE AND DIFFERENT EFFECTS ON SYNTHESIS OF HEPATIC PROTEINS IN NORMAL HUMANS

These studies tested the hypothesis that physiological increments in p lasma insulin concentrations have selective effects on the synthesis o f hepatic proteins in humans. Leucine kinetics and fractional syntheti c rates of albumin, fibrinogen, antithrombin III, and apoB-100 were de termined in 6 normal subjects, on two different occasions during eithe r the infusion of saline (control study) or a euglycemic-hyperinsuline mic (0.4 mU . kg-1 . min-1 for 240 min) clamp, by a primed-constant in fusion of [1-C-14]Leu. The insulin infusion significantly decreased th e rates of nonoxidative Leu disposal (1.70 +/- 0.10 vs. control 2.06 /- 0.09 mol . kg-1 . min-1), increased the albumin (7.2 +/- 0.4 vs. 6. 2 +/- 0.6%/day), decreased the fibrinogen (18 +/- 1 vs. 23 +/- 2%/day) , and antithrombin III (28 +/- 3 vs. 40 +/- 4%/day) fractional synthet ic rate, whereas it did not affect the total apoB-100 (49 +/- 5 vs. 52 +/- 6%/day) fractional synthetic rate. Thus, the insulin-induced decr ement in the estimates of whole-body protein synthesis (nonoxidative L eu disposal) represents the mean result of opposite effects of hyperin sulinemia on the synthesis of proteins with different functions. The p ositive effect of insulin on albumin synthesis may play an important a nabolic role during nutrient absorption by promoting the capture of a relevant amount of dietary essential amino acids into the protein, whe reas the negative effect of insulin on fibrinogen synthesis might, at least partially, account for the increased plasma fibrinogen concentra tions previously reported in poorly controlled diabetic patients.