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

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

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.

MeSH terms

  • Adult
  • Biological Transport
  • Fatty Acids, Nonesterified / blood*
  • Fluorodeoxyglucose F18 / pharmacokinetics*
  • Glucose / metabolism*
  • Humans
  • Insulin / physiology*
  • Kinetics
  • Liver / metabolism*
  • Male
  • Phosphorylation
  • Positron-Emission Tomography
  • Radiopharmaceuticals / pharmacokinetics
  • Reference Values

Substances

  • Fatty Acids, Nonesterified
  • Insulin
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Glucose