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 con-trast, insulin deficiency does not change, or, paradoxically, in-creases 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 syn-thetic rates of individual proteins, we determined whole body protein synthesis and albumin and fibrinogen fractional syn-thetic rates using 5-h simultaneous infusions of [14Cjleucine and I13C]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 proteo-lysis by 35 % and leucine oxidation by-100%, but did not change 3CO2 recovery from NaH13CO3 or estimates of whole body protein synthesis (P = 0.21). Insulin deficiency was asso-ciated with a 29 % decrease (P < 0.03) in the albumin fractional synthetic rate but a 50 % increase (P < 0.03) in that of fi-brinogen. These data provide strong evidence that albumin synthesis in humans is an insulin-sensitive process, a conclusion consis-tent with observations in rats. The increase in fibrinogen synthe-sis 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 ofthe summation of differ-ential effects of insulin deficiency on the synthesis of specifi