Non-esterified fatty acids impair insulin-mediated glucose uptake and disposition in the liver.
OBJECTIVE
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
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.
Iozzo
P
P
Turku PET Centre, University of Turku, Finland. patricia.iozzo@ifc.cnr.it.|PET Laboratory, Institute of Clinical Physiology, National Research Council (CNR), Via Moruzzi 1, 56100, Pisa, Italy. patricia.iozzo@ifc.cnr.it.
Lautamaki
R
R
Turku PET Centre, University of Turku, Finland.
Geisler
F
F
Turku PET Centre, University of Turku, Finland.
Virtanen
K A
KA
Turku PET Centre, University of Turku, Finland.
Oikonen
V
V
Turku PET Centre, University of Turku, Finland.
Haaparanta
M
M
Turku PET Centre, University of Turku, Finland.
Yki-Jarvinen
H
H
Department of Medicine, Division of Diabetes, University of Helsinki, Finland.
Ferrannini
E
E
PET Laboratory, Institute of Clinical Physiology, National Research Council (CNR), Via Moruzzi 1, 56100, Pisa, Italy.|Department of Internal Medicine, University of Pisa School of Medicine, Italy.
Knuuti
J
J
Turku PET Centre, University of Turku, Finland.
Nuutila
P
P
Turku PET Centre, University of Turku, Finland.|Department of Medicine, University of Turku, Finland.
D000328:Adult; D001692:Biological Transport; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012016:Reference Values
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose