DIFFERENTIAL-EFFECTS OF INSULIN DEFICIENCY ON ALBUMIN AND FIBRINOGEN SYNTHESIS IN HUMANS

Insulin deficiency decreases tissue protein synthesis, albumin mRNA concentration, and albumin synthesis in rats. In contrast, insulin deficiency does not change, or, paradoxically, increases estimates of whole body protein synthesis in humans. To determine if such estimates of whole body protein synthesis could obscure potential differential effects of insulin on the synthetic rates of individual proteins, we determined whole body protein synthesis and albumin and fibrinogen fractional synthetic rates using 5-h simultaneous infusions of [C-14]leucine and [C-13]bicarbonate, in six type 1 diabetics during a continuous i.v. insulin infusion (to maintain euglycemia) and after short-term insulin withdrawal (12 +/- 2 h). Insulin withdrawal increased (P < 0.03) whole body proteolysis by almost-equal-to 35% and leucine oxidation by approximately 100%, but did not change (CO2)-C-13 recovery from (NaHCO3)-C-13 or estimates of whole body protein synthesis (P = 0.21). Insulin deficiency was associated with a 29% decrease (P < 0.03) in the albumin fractional synthetic rate but a 50% increase (P < 0.03) in that of fibrinogen. These data provide strong evidence that albumin synthesis in humans is an insulin-sensitive process, a conclusion consistent with observations in rats. The increase in fibrinogen synthesis during insulin deficiency most likely reflects an acute phase protein response due to metabolic stress. These data suggest that the absence of changes in whole body protein synthesis after insulin withdrawal is the result of the summation of differential effects of insulin deficiency on the synthesis of specific body proteins.