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Diabetologia. 2004 Jul;47(7):1149-1156. doi: 10.1007/s00125-004-1443-2. Epub 2004 Jul 9.

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

Author information

1
Turku PET Centre, University of Turku, Finland. patricia.iozzo@ifc.cnr.it.
2
PET Laboratory, Institute of Clinical Physiology, National Research Council (CNR), Via Moruzzi 1, 56100, Pisa, Italy. patricia.iozzo@ifc.cnr.it.
3
Turku PET Centre, University of Turku, Finland.
4
Department of Medicine, Division of Diabetes, University of Helsinki, Finland.
5
PET Laboratory, Institute of Clinical Physiology, National Research Council (CNR), Via Moruzzi 1, 56100, Pisa, Italy.
6
Department of Internal Medicine, University of Pisa School of Medicine, Italy.
7
Department of Medicine, University of Turku, Finland.

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 [(18)F]-2-fluoro-2-deoxyglucose ([(18)F]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 [(18)F]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.

PMID:
15243703
DOI:
10.1007/s00125-004-1443-2
[Indexed for MEDLINE]

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