You are viewing a version of a model that has been updated. To access the latest version, and a more detailed display please go here.

DDMODEL00000131: Dose-response characteristics of insulin action on glucose metabolism

  public model
Short description:
Model of glucose kinetics and insulin action from non-steady-state labeled data
PharmML (0.6.1)
  • Dose-response characteristics of insulin action on glucose metabolism: a non-steady-state approach.
  • Natali A, Gastaldelli A, Camastra S, Sironi AM, Toschi E, Masoni A, Ferrannini E, Mari A
  • American journal of physiology. Endocrinology and metabolism, 5/2000, Volume 278, Issue 5, pages: E794-801
  • Metabolism Unit of the Consiglio Nazionale delle Ricerche Institute of Clinical Physiology and Department of Internal Medicine, University of Pisa, 56126 Pisa, Italy.
  • The traditional methods for the assessment of insulin sensitivity yield only a single index, not the whole dose-response curve information. This curve is typically characterized by a maximally insulin-stimulated glucose clearance (Cl(max)) and an insulin concentration at half-maximal response (EC(50)). We developed an approach for estimating the whole dose-response curve with a single in vivo test, based on the use of tracer glucose and exogenous insulin administration (two steps of 20 and 200 mU x min(-1) x m(-2), 100 min each). The effect of insulin on plasma glucose clearance was calculated from non-steady-state data by use of a circulatory model of glucose kinetics and a model of insulin action in which glucose clearance is represented as a Michaelis-Menten function of insulin concentration with a delay (t(1/2)). In seven nondiabetic subjects, the model predicted adequately the tracer concentration: the model residuals were unbiased, and their coefficient of variation was similar to the expected measurement error (approximately 3%), indicating that the model did not introduce significant systematic errors. Lean (n = 4) and obese (n = 3) subjects had similar half-times for insulin action (t(1/2) = 25 +/- 9 vs. 25 +/- 8 min) and maximal responses (Cl(max) = 705 +/- 46 vs. 668 +/- 259 ml x min(-1) x m(-2), respectively), whereas EC(50) was 240 +/- 84 microU/ml in the lean vs. 364 +/- 229 microU/ml in the obese (P < 0.04). EC(50) and the insulin sensitivity index (ISI, initial slope of the dose-response curve), but not Cl(max), were related to body adiposity and fat distribution with r of 0.6-0.8 (P < 0.05). Thus, despite the small number of study subjects, we were able to reproduce information consistent with the literature. In addition, among the lean individuals, t(1/2) was positively related to the ISI (r = 0.72, P < 0.02). We conclude that the test here presented, based on a more elaborate representation of glucose kinetics and insulin action, allows a reliable quantitation of the insulin dose-response curve for whole body glucose utilization in a single session of relatively short duration.
Roberto Bizzotto
Annotations have not been checked.
This model is not certified.
  • Model owner: Roberto Bizzotto
  • Submitted: Dec 29, 2015 3:56:12 PM
  • Last Modified: May 18, 2016 4:11:44 PM
  • Version: 7 public model Download this version
    • Submitted on: May 18, 2016 4:11:44 PM
    • Submitted by: Roberto Bizzotto
    • With comment: Updated model annotations.
  • Version: 4 public model Download this version
    • Submitted on: Dec 29, 2015 3:56:12 PM
    • Submitted by: Roberto Bizzotto
    • With comment: Edited model metadata online.