title: Human insulin dynamics in women: a physiologically based model.
abstract: Currently available models of insulin dynamics are mostly based on the classical compartmental structure and, thus, their physiological utility is limited. In this work, we describe the development of a physiologically based model and its application to data from 154 patients who underwent an insulin-modified intravenous glucose tolerance test (IM-IVGTT). To determine the time profile of endogenous insulin delivery without using C-peptide data and to evaluate the transcapillary transport of insulin, the hepatosplanchnic, renal, and peripheral beds were incorporated into the circulatory model as separate subsystems. Physiologically reasonable population mean estimates were obtained for all estimated model parameters, including plasma volume, interstitial volume of the peripheral circulation (mainly skeletal muscle), uptake clearance into the interstitial space, hepatic and renal clearance, as well as total insulin delivery into plasma. The results indicate that, at a population level, the proposed physiologically based model provides a useful description of insulin disposition, which allows for the assessment of muscle insulin uptake.
authors.affiliation: Department of Pharmacology, Martin Luther University, Halle-Wittenberg, Halle, Germany; michael.weiss@medizin.uni-halle.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiss
authors.affiliation: Metabolic Unit, National Research Council Neuroscience Institute, Padova, Italy;
authors.forename: Andrea
authors.initials: A
authors.lastname: Tura
authors.affiliation: Gender Medicine, Medical University of Vienna, Vienna, Austria; and.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kautzky-Willer
authors.affiliation: Metabolic Unit, National Research Council Neuroscience Institute, Padova, Italy;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California.
authors.forename: David Z
authors.initials: DZ
authors.lastname: D'Argenio
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D016640:Diabetes, Gestational / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D065669:Hepatobiliary Elimination; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism; D011247:Pregnancy; D065667:Renal Elimination
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin
keywords: circulatory model; insulin delivery; insulin transport; intravenous glucose test; population analysis