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01.07.2004 | Article

Non-esterified fatty acids impair insulin-mediated glucose uptake and disposition in the liver

verfasst von: P. Iozzo, R. Lautamaki, F. Geisler, K. A. Virtanen, V. Oikonen, M. Haaparanta, H. Yki-Jarvinen, E. Ferrannini, J. Knuuti, P. Nuutila

Erschienen in: Diabetologia | Ausgabe 7/2004

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Abstract

Aims/hypothesis

We investigated the effect of elevated circulating NEFA on insulin-mediated hepatic glucose uptake (HGU) and whole-body glucose disposal (M) in eight healthy male subjects.

Methods

Studies were performed using positron emission tomography (PET) and [¹⁸F]-2-fluoro-2-deoxyglucose ([¹⁸F]FDG) during euglycaemic hyperinsulinaemia (0–120 min) and an Intralipid/heparin infusion (IL/Hep; −90–120 min). On a different day, similar measurements were taken during euglycaemic hyperinsulinaemia and saline infusion (SAL). Graphical and compartmental analyses were used to model liver data.

Results

Circulating NEFA increased approximately three-fold during IL/Hep, and declined by 81±7% in the SAL study (p≤0.01). Both M (−28±7%) and HGU (−25±9%) were significantly lowered by NEFA elevation (p=0.004 and p=0.035 respectively). In the whole data set, the decreases in M and HGU were positively correlated (r=0.78, p=0.038). No evidence of [¹⁸F]FDG outflow was detected during the scanning time. HGU was correlated with the phosphorylation rate parameter (r=0.71, p=0.003) as derived by compartmental modelling.

Conclusions/interpretation

In healthy men, NEFA impair insulin-mediated HGU and whole-body glucose uptake to a similar extent. Our data suggest that multiple intracellular NEFA targets may concur to down-regulate glucose uptake by the liver.

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Titel: Non-esterified fatty acids impair insulin-mediated glucose uptake and disposition in the liver
verfasst von: P. Iozzo
R. Lautamaki
F. Geisler
K. A. Virtanen
V. Oikonen
M. Haaparanta
H. Yki-Jarvinen
E. Ferrannini
J. Knuuti
P. Nuutila
Publikationsdatum: 01.07.2004
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 7/2004
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-004-1443-2

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