Hepatic insulin sensitivity assessed by integrated model of hepatic and peripheral glucose regulation.
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-(2)H(2)]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.
Tokuyama
Kumpei
K
Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8574 Japan. tokuyama@taiiku.tsukuba.ac.jp
Nagasaka
Shoichiro
S
Mori
Schuuichi
S
Takahashi
Nirei
N
Kusaka
Ikuyo
I
Kiyonaga
Akira
A
Tanaka
Hiroaki
H
Shindo
Munehiro
M
Ishibashi
Shun
S
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D015444:Exercise / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000502:physiology*; D008019:Life Style; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008875:Middle Aged; D008954:Models, Biological; D012189:Retrospective Studies; D012420:Running; D057185:Sedentary Behavior
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose