Reduced hepatic insulin clearance in rats with dietary-induced obesity.

Insulin uptake in the in situ perfused liver from rats that were moderately obese after overfeeding was diminished in comparison with controls. The obese rats had higher levels of portal free fatty acids (FFA) and liver triglyceride contents but not of insulin concentration in the portal vein. There were strong negative correlations between hepatic triglyceride and insulin clearance (r approximately 0.8-0.9). The perfusions were performed with lower FFA concentrations than those in vivo in the portal vein. It is suggested that the inhibited insulin uptake in the obese rats was due to exposure of these livers in vivo to elevated FFA concentrations, and that this inhibition remained during the experiment and was associated with the triglyceride contents of the livers. It is also suggested that this mechanism was responsible for the moderate peripheral hyperinsulinemia seen in these rats. A mechanism of regulation of insulin uptake in the liver via FFA and liver triglyceride might be of importance in several conditions with hyperinsulinemia and known elevation of portal FFA, and liver triglyceride contents.