A1 Refereed original research article in a scientific journal
Non-esterified fatty acids impair insulin-mediated glucose uptake and disposition in the liver
Authors: Iozzo P, Lautamaki R, Geisler F, Virtanen KA, Oikonen V, Haaparanta M, Yki-Jarvinen H, Ferrannini E, Knuuti J, Nuutila P
Publisher: SPRINGER
Publication year: 2004
Journal: Diabetologia
Journal name in source: DIABETOLOGIA
Journal acronym: DIABETOLOGIA
Volume: 47
Issue: 7
First page : 1149
Last page: 1156
Number of pages: 8
ISSN: 0012-186X
DOI: https://doi.org/10.1007/s00125-004-1443-2
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 [F-18]-2-fluoro-2-deoxyglucose ([F-18]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 (pless than or equal to0.01). 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 [F-18]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 [F-18]-2-fluoro-2-deoxyglucose ([F-18]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 (pless than or equal to0.01). 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 [F-18]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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