The System Dynamics model described in this paper presents a new approach to the mechanisms of subcutaneous absorption of dissolved insulin. Experimental investigations have shown that the apparent absorption constant varies in time, and that this variation depends both on the volume and the concentration of the injected insulin. Our model assumes that insulin is present in the subcutaneous depot in three forms: (i) a dimeric form, (ii) a hexameric form, and (iii) an immobile form in which the molecules are bound in the tissue. The model describes how diffusion and absorption gradually reduce the insulin concentrations and thereby shift the balance between three forms according to usual laws of chemical kinetics. By assuming that only dimeric molecules can penetrate the capillary wall, we have found that the model can fully account for the observed variations in the absorption rate. At the same time the model can be used to determine at least 5 parameters characterizing the involved processes: the diffusion constant for insulin in the subcutaneous tissue, the absorption constant for dimeric insulin, the equilibrium constant for the dimeric/hexameric polymerization process, the binding capacity for the insulin in the tissue, and the average life time for insulin in bound state. Combined with a simplified model of the distribution and degradation of insulin in the body, the diffusion-absorption model has been used to simulate different insulin delivery schedules, i.e. a single major injection contra dosage with infusion pump. The model has shown that a pump repetition frequency of 1-2/hr can secure a sufficiently constant plasma insulin concentration.

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Date created

• 1984

Type

• Document

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• Processing documentation available at: https://wiki.albany.edu/display/SCA/Processing+Ingested+Digital+Files

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• Creative Commons BY-NC-ND Attribution-NonCommercial-NoDerivs 4.0 International

  
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6e5cbea1fd05527880f389afd8fb85d1

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Collection

System Dynamic Society Records

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• This collection is part of the University Archives