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 plasma insulin concentrations have selective effects on the synthesis of hepatic proteins in humans. Leucine kinetics and fractional synthetic rates of albumin, fibrinogen, antithrombin III, and apoB-100 were determined in 6 normal subjects, on two different occasions during either the infusion of saline (control study) or a euglycemic-hyperinsulinemic (0.4 mU . kg-1 . min-1 for 240 min) clamp, by a primed-constant infusion of [1-C-14]Leu. The insulin infusion significantly decreased the 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 synthetic rate, whereas it did not affect the total apoB-100 (49 +/- 5 vs. 52 +/- 6%/day) fractional synthetic rate. Thus, the insulin-induced decrement in the estimates of whole-body protein synthesis (nonoxidative Leu disposal) represents the mean result of opposite effects of hyperinsulinemia on the synthesis of proteins with different functions. The positive effect of insulin on albumin synthesis may play an important anabolic role during nutrient absorption by promoting the capture of a relevant amount of dietary essential amino acids into the protein, whereas the negative effect of insulin on fibrinogen synthesis might, at least partially, account for the increased plasma fibrinogen concentrations previously reported in poorly controlled diabetic patients.