Related Experiment Videos
Kinetic models for insulin disappearance from plasma in man
1Department of Medicine E, Frederiksberg Hospital, Copenhagen.
Danish Medical Bulletin
|April 1, 1990
Summary
Insulin disappearance from plasma follows saturation kinetics in normal subjects and at high concentrations in type I diabetics, contrasting previous first-order models. First-order kinetics best describes insulin clearance at physiological levels in type I diabetics.
Area of Science:
- Pharmacokinetics and Metabolism
- Endocrinology
- Diabetes Research
Background:
- Established models often use first-order kinetics to describe insulin disappearance from plasma.
- Emerging evidence suggests saturation kinetics may be more accurate for insulin clearance.
- A discrepancy exists between general assumptions and observed insulin kinetics.
Purpose of the Study:
- To evaluate three distinct models of insulin kinetics: first-order, saturation (Michaelis-Menten), and a combined model.
- To determine the most accurate model for describing insulin disappearance in normal and type I diabetic subjects under varying insulin concentrations.
- To investigate the influence of insulin-receptor binding and physiological conditions on insulin kinetics.
Main Methods:
- Constant intravenous infusions of insulin at varying rates to achieve steady-state plasma insulin concentrations.
- Glucose clamp technique to maintain euglycaemia or moderate hyperglycemia.
- Comparison of model fits using validation procedures in normal and type I diabetic individuals.
Main Results:
- Saturation kinetics alone (Model 2) best described insulin disappearance in normal subjects across physiological and supraphysiological insulin levels.
- In type I diabetics, saturation kinetics predominated at supraphysiological levels, while first-order kinetics (Model 3) was optimal at physiological levels.
- Insulin clearance was independent of insulin species and clamp glucose levels; Km values correlated with insulin-receptor binding dissociation constants (Kd).
Conclusions:
- Insulin disappearance from plasma is best described by saturation kinetics in normal individuals and at high concentrations in type I diabetics.
- A minimal model of first-order kinetics is appropriate for physiological insulin concentrations in type I diabetics.
- Saturation kinetics likely relates to insulin-receptor binding saturation, with potential contributions from altered regional blood flow at hyperinsulinemia.