P Iozzo1,2, R Lautamaki3, F Geisler3, K A Virtanen3, V Oikonen3, M Haaparanta3, H Yki-Jarvinen4, E Ferrannini5,6, J Knuuti3, P Nuutila3,7. 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.
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.
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