Interstitial insulin kinetic parameters for a 2-compartment insulin model with saturable clearance

Abstract

Glucose-insulin system models are commonly used for identifying insulin sensitivity. With physiological, 2-compartment insulin kinetics models, accurate kinetic parameter values are required for reliable estimates of insulin sensitivity.This study uses data from 6 published microdialysis studies to determine the most appropriate parameter values for the transcapillary diffusion rate (nI) and cellular insulin clearance rate (nC).The 6 studies (12 data sets) used microdialysis techniques to simultaneously obtain interstitial and plasma insulin concentrations. The reported plasma insulin concentrations were used as input and interstitial insulin concentrations were simulated with the interstitial insulin kinetics sub-model. These simulated results were then compared to the reported interstitial measurements and the most appropriate set of parameter values was determined across the 12 data sets by combining the results.Interstitial insulin kinetic parameters values nI = nC = 0.0060 min -1 were shown to be the most appropriate. These parameter values are associated with an effective, interstitial insulin half-life, t½ = 58 minutes, within the range of 25-130 minutes reported by others.

Human insulin dynamics in women: a physiologically based model

“…For the transendothelial insulin transport into the interstitial space, a permeabilitysurface product (or uptake clearance) of 75.8 ml/min was estimated (PS in the model), compared with a value of 105 ml/min measured directly in human skeletal muscle using microdialysis (13). A different model was used by Pretty et al (24) to calculate uptake rate constants from arterial and interstitial insulin concentration data taken from various sources in the literature. Our results are also within the range of PS values (11 and 91 ml/min) reported in (24).…”

“…A different model was used by Pretty et al (24) to calculate uptake rate constants from arterial and interstitial insulin concentration data taken from various sources in the literature. Our results are also within the range of PS values (11 and 91 ml/min) reported in (24). Our results do not suggest a saturable uptake of insulin, which is in agreement with some findings (3,26), but not with others (16).…”

Microneedle Assays for Continuous Health Monitoring: Challenges and Solutions

“…Transdermal biosensing has been introduced as an ideal candidate for continuous, real-time monitoring, as it enables biomarker measurement in a non- or minimally invasive manner. , Transdermal biosensors analyze interstitial fluid (ISF), the fluid which is present in the lowermost skin layer of the dermis, for biomarker measurements. − Compared to other body fluids, ISF has the most similar molecular composition to blood plasma and possesses other unique features including biomarkers of medical relevance. − The absence of clotting factors in ISF also allows for a prolonged continuous measurement. Simple and effective methods that enable the comprehensive analysis of ISF can lead to transformative advances in bio-diagnostic technologies. ,,− These approaches are not only minimally invasive and painless but also ideally suited for point of care (POC) and resource-limited settings. ,,, …”