Glucose uptake and pulsatile insulin infusion: euglycaemic clamp and [3-3H]glucose studies in healthy subjects

To test the hypothesis that insulin has a greater effect on glucose metabolism when given as pulsatile than as continuous infusion, a 354-min euglycaemic clamp study was carried out in 8 healthy subjects. At random order soluble insulin was given intravenously either at a constant rate of 0.45 mU/kg X min or in identical amounts in pulses of 1 1/2 to 2 1/4 min followed by intervals of 10 1/2 to 9 3/4 min. Average serum insulin levels were similar during the two infusion protocols, but pulsatile administration induced oscillations ranging between 15 and 62 microU/ml. Glucose uptake expressed as metabolic clearance rate (MCR) for glucose was significantly increased during pulsatile insulin delivery as compared with continuous administration (270-294 min: 8.7 +/- 0.7 vs 6.8 +/- 0.9 ml/kg X min, P less than 0.01, and 330-354 min: 8.9 +/- 0.5 vs 7.4 +/- 0.9 ml/kg X min, P less than 0.05). The superior efficacy of pulsatile insulin delivery on glucose uptake was not consistently found until after 210 min of insulin administration. In both infusion protocols, endogenous glucose production as estimated by the [3-3H]glucose infusion technique was suppressed to insignificant values. Finally, the effect of insulin on endogenous insulin secretion and lipolysis as assessed by changes in serum C-peptide and serum FFA was uninfluenced by the infusion mode. In conclusion, insulin infusion resulting in physiological serum insulin levels enhances glucose uptake in peripheral tissues in healthy subjects to a higher degree when given in a pulsed pattern mimicking that of the normal endocrine pancreas than when given as a continuous infusion.