Effect of a two hour proinsulin infusion on the glucose lowering potency of a following insulin injection

To test whether proinsulin pretreatment can increase insulin effects, we studied the glucose lowering effect of insulin given intravenously as a bolus (9 mU/kg) following a two hour infusion of proinsulin (3 micrograms/kg body weight.h) in 11 healthy volunteers. Insulin was given directly after proinsulin infusion and two hours later. On a control day dilution medium has been infused only. The proinsulin dose chosen was able to reduce blood glucose significantly (from 4.30 to 3.81 mmol/l, P less than 0.05) without leading to increases in counterregulatory hormones. There were no significant changes in glucagon, growth hormone, adrenaline and noradrenaline, while cortisol showed a decline according to its diurnal rhythm during proinsulin infusion and control. Free fatty acids and glycerol as indicators of fat metabolism were reduced by 28.0% and 54.9% respectively, compared to reduction by 16.0% and 23.4% during control. Insulin injection directly after proinsulin infusion decreased blood glucose from 3.81 to 2.52 mmol/l. The decrease during control was from 4.38 to 2.98 mmol/l. Two hours after proinsulin infusion, blood glucose was decreased by insulin injection from 4.09 to 2.98 mmol/l, compared to a decrease from 4.08 to 3.19 mmol/l during control. No statistical significant effect of the preceding proinsulin infusion on insulin action could be demonstrated. Proinsulin seems to have no specific effect on either glucose or fat metabolism.