Assessment of proinsulin's effects on intermediary metabolism using the forearm technique in normal man

We have compared the effects of human proinsulin and insulin on forearm metabolism. Seven normal, non-obese subjects were infused with 386 pmol/kg per hour of proinsulin and 180 pmol/kg per hour of insulin using the euglycaemic clamp technique. Glucose appearance and utilization rates were quantified using a primed continuous infusion of [6',6'-2H2]glucose. Mean blood glucose was 4.1 +/- 0.1 and 4.1 +/- 0.2 mmol/l during proinsulin and insulin infusions respectively. Basal insulin concentrations increased from 0.02 +/- 0.01 to 0.25 +/- 0.03 nmol/l. The proinsulin infusion was chosen to give steady-state levels approximately 20-fold higher on a molar basis than those of insulin, based on previous findings that proinsulin has only 5% the biological potency of insulin. Basal proinsulin concentrations increased from 0.003 to 5.4 +/- 0.3 nmol/l. Hepatic glucose production was suppressed similarly during the last hour of each hormone infusion: 0.07 +/- 0.16 (proinsulin, P), and 0.01 +/- 0.13 (insulin, I) mg/kg per minute. Glucose disposal, however, was significantly increased during the final hour of the insulin infusion: 4.7 +/- 0.4 (I) and 3.4 +/- 0.2 (P) mg/kg per minute (P = 0.025). Net forearm glucose uptake (FGU) increased by a greater amount during insulin compared with proinsulin infusion: 1.44 +/- 0.02 (I) and 0.71 +/- 0.01 (P) mumol/100 ml forearm per minute (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)