Hepatic Insulin Sensitivity Assessed by Integrated Model of Hepatic and Peripheral Glucose Regulation

Abstract

Background:

The integrated model of hepatic and peripheral glucose metabolism incorporates a model for liver glucose metabolism into the two-compartment minimal model framework to describe endogenous glucose kinetics during a labeled intravenous glucose tolerance test (IVGTT). This model also provides a parametric description of endogenous glucose production (EGP). The present study extended the theoretical potential of the model by defining hepatic glucose effectiveness (hS _G ²) as the ability of glucose per se to inhibit EGP and hepatic insulin sensitivity (hS ₁ ²) as the ability of insulin to enhance glucose suppression of EGP.

Methods:

As a retrospective data base review of our previous study, we re-analyzed time courses of exogenous and endogenous glucose concentration during [6,6-²H₂]glucose-labeled IVGTT (0.3 g/kg glucose), performed in 11 exercise-trained and 12 age-matched sedentary subjects. Model parameters of the two-compartment minimal model and of liver glucose metabolism were simultaneously identified to assess insulin sensitivity specific to stimulate glucose uptake (S ₁ ^2*) and that specific to inhibit EGP (hS ₁ ²). The abilities of glucose per se to stimulate its own uptake (S _G ^2*) and to inhibit EGP (hS _G ²) were also estimated.

Results:

Parameters of the integrated model were identified in all the subjects. Hepatic insulin sensitivity consisted of about one-third of total insulin sensitivity (S ₁ ^2* + hS ₁ ²). Compared with the sedentary subjects, S ₁ ^2*, hS ₁ ², hS _G ² of the trained subjects were greater.

Conclusions:

Because insulin resistance in liver and peripheral tissue may play a differential role in the pathogenesis of diabetes, this analysis can serve as a simple one-step approach to obtain metabolic indexes specific to EGP suppression and stimulating glucose uptake.