title: Non-esterified fatty acids impair insulin-mediated glucose uptake and disposition in the liver.
abstract: 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.
authors.affiliation: 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.
authors.forename: P
authors.initials: P
authors.lastname: Iozzo
authors.affiliation: Turku PET Centre, University of Turku, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Lautamaki
authors.affiliation: Turku PET Centre, University of Turku, Finland.
authors.forename: F
authors.initials: F
authors.lastname: Geisler
authors.affiliation: Turku PET Centre, University of Turku, Finland.
authors.forename: K A
authors.initials: KA
authors.lastname: Virtanen
authors.affiliation: Turku PET Centre, University of Turku, Finland.
authors.forename: V
authors.initials: V
authors.lastname: Oikonen
authors.affiliation: Turku PET Centre, University of Turku, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Haaparanta
authors.affiliation: Department of Medicine, Division of Diabetes, University of Helsinki, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Yki-Jarvinen
authors.affiliation: 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.
authors.forename: E
authors.initials: E
authors.lastname: Ferrannini
authors.affiliation: Turku PET Centre, University of Turku, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Knuuti
authors.affiliation: Turku PET Centre, University of Turku, Finland.|Department of Medicine, University of Turku, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Nuutila
mesh_terms: 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
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose