Insulin Control of Glucose Metabolism in Man (original) (raw)
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Effect of insulin on the distribution and disposition of glucose in man
1985
Understanding the influence of insulin on glucose turnover is the key to interpreting a great number of metabolic situations. Little is known, however, about insulin's effect on the distribution and exchange of glucose in body pools. We developed a physiological compartmental model to describe the kinetics of plasma glucose in normal man in the basal state and under steady-state conditions of euglycemic hyperinsulinemia.
A Model of the Kinetics of Insulin in Man
Journal of Clinical Investigation, 1974
We suggest that the combined use of glucose-clamp and kinetic-modeling techniques should aid in the delineation of pathophysiologic states affecting glucose and insulin metabolism.
Diabetologia, 1985
The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees of β-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient β-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and β-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p < 0.0001), the fasting insulin concentration (Rs = 0.81, p < 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p < 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient β-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p < 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p < 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for β-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
Dose-response characteristics of insulin action on glucose metabolism: a non-steady-state approach
American journal of physiology. Endocrinology and metabolism, 2000
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 simila...
A model for glucose control of insulin secretion during 24 h of free living
Diabetes, 2001
The aim of this work was to develop a mathematical model describing the functional dependence of insulin secretion on plasma glucose concentrations during 24 h of free living. We obtained hourly central venous blood samples from a group of healthy volunteers who spent 24 h in a calorimetric chamber, where they consumed standardized meals. Insulin secretory rates were reconstructed from plasma C-peptide concentrations by deconvolution. The relationship between insulin release and plasma glucose concentrations was modeled as the sum of three components: a static component (describing the dependence on plasma glucose concentration itself, with an embedded circadian oscillation), a dynamic component (modeling the dependence on glucose rate of change), and a residual component
2003
In the current study, glucose -insulin interaction was investigated on the basis of measured data obtained by the intravenous glucose tolerance test (IVGTT) in healthy subjects. The study objective was to propose a circulatory physiologically-based model of glucose -insulin interaction, capable of quantifying processes that develop in the body after the glucose load, i. e. the glucose uptake by body cells and cessation of the glucose output from liver. The proposed model is a new alternative to the classic minimal model and its recent variants, which are currently in the use for the evaluation of measurements from IVGTT. Examples are given, showing results of the fits of the proposed model to measured plasma concentration-time profiles of glucose of the subjects enrolled. Key words: glucose-insulin interaction, circulatory model, time delay, system approach.
Human insulin dynamics in women: a physiologically based model
American journal of physiology. Regulatory, integrative and comparative physiology, 2015
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 physiological-based model and its application to data from 154 patients who underwent an insulin modified intravenous glucose tolerance test (IM IVGTT). In order 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 l...
Diabetic Medicine, 2003
Multiple defects in the regulation of glucose metabolism are believed to play a role in the pathophysiology of Type 2 diabetes mellitus . Thus, basal rates of glucose production are often elevated , and suppression of glucose production (GP) as well as stimulation of glucose disappearance ( R d) by insulin, is impaired in Type 2 diabetes . In the study of this issue, the primed-constant tracer infusion method plays a major role. This method is combined with the euglycaemic hyperinsulinaemic clamp technique to assess the effects of insulin on glucose metabolism, independent of the effects of hyperglycaemia per se .