A model of the kinetics of insulin in man

Abstract

The study of the kinetics of insulin in man combines experimental features which obviate two of the major problems in previous insulin studies: The use of radioiodinated insulin as a tracer has been shown to be inappropriate, since its metabolism differs markedly from that of the native hormone. Therefore, porcine insulin was administered by procedures which raised insulin levels in arterial plasma into the upper physiologic range. Hypoglycemia was prevented by adjusting the rate of an intravenous infusion of glucose in order to control the blood glucose concentration (the glucose clamp technique). Also estimation of a single biological half time of insulin after pulse injection of the hormone has been shown to be inappropriate since plasma insulin disappearance curves are multiexponential. Therefore, the SAAM 25 computer program was used in order to define the parameters of a three compartment insulin model. The combined insulin mass of the three compartments (expressed as plasma equivalent volume) is equal to insulin space (15.7% body wt). Compartment 1 is apparently the plasma space (4.5%). The other two compartments are extra vascular: compartment 2 is small (1.7%) and equilibrates rapidly with plasma; compartment 3 is large (9.5%) and equilibrates slowly with plasma. The SAAM 25 program can simulate the buildup and decay of insulin in compartments 2 and 3 which cannot be assayed directly. Insulin in compartment 3 was found to correlate remarkably with the time course of the servo controlled glucose infusion. Under conditions of a steady state arterial glucose level, glucose infusion is a measure of glucose utilization. It is concluded that compartment 3 insulin (rather than plasma insulin) is a more direct determinant of glucose utilization.