Metabolic Clearance Rate of Insulin Is Not Saturable within the Physiological Range

Abstract

The plasma concentration of insulin is determined by pancreatic beta cell secretion and the metabolic clearance of the hormone. It has been suggested that the concentration of insulin determines its metabolic clearance rate. Also, some reports suggest that clearance is saturable and insulin kinetics are non-linear even within physiologic ranges. We assessed the metabolic clearance rate of insulin at different physiologic concentrations to access if clearance changes with concentration. Using the dog model (n=12), insulin was infused peripherally at 3 incremental rates (dose-response) during the euglycemic clamp. Each infusion rate spanned 90mins, and the last 30mins was considered the steady state. The metabolic clearance rate of insulin was calculated as the ratio of the infusion rate to the steady state plasma concentration. The 3 infusion rates, 1.5, 3.0 and 4.5pmol/kg/min yielded steady state plasma insulin concentrations of 92 ± 8, 165 ± 12 and 256 ± 18pM respectively. The metabolic clearance rate of insulin was consistent and independent of dose (17.8 ±1.7, 19.1 ±1.2 and 18.6 ±1.4 ml/kg/min; p = ns) across the different plasma insulin infusion rates. Also, we found a strong linear correlation (r = 0.99) between the infusion rates and steady state insulin concentrations. Insulin kinetics are linear and the metabolic clearance of insulin is not saturable within physiologic ranges in the conscious dog. Though it’s possible that the site of degradation (i.e., liver vs. periphery) may change with dose.These data demonstrate that changing concentrations of plasma insulin within physiologic concentrations does not change the rate of insulin removal from the plasma. Disclosure I. Asare Bediako: None. R.L. Paszkiewicz: None. O.O. Woolcott: None. R.N. Bergman: Advisory Panel; Self; Ingredion, Inc.. Research Support; Self; AstraZeneca. Consultant; Self; GI Dynamics Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Self; Novo Nordisk A/S.