Effect of the Peroxisome Proliferator Perfluoro-n-Decanoic Acid on GlucoseTransport in the Isolated Perfused Rat Liver

摘要

The perfluorinated carboxylic acid, perfluoro-n-decanoic acid (PFDA), is a knownperoxisome proliferator which displays toxicity in rodents. Using a paired-tracer first-pass extraction technique, the effect of PFDA on hepatic glucose transport was determined in the isolated perftised rat liver. In brief, livers isolated from PFDA-treated and control rats on day 5 posttreatment were administered the radiolabeled glucose analog, 3-O-'4Cmethyl-D-glucose (14C3-O-MG) in addition to tfructose-1-3H(N)sucrose (3Hsucrose), which served as a measure of extracellular volume. Hepatic glucose transport was calculated from the change in the ratio 14Cs-O-MG/3Hsucrose during passage through the liver. Data from this study indicate that PFDA inhibits hepatic glucose transport. Percent hepatic glucose extraction is 1.8-fold greater in controls than in PFDA-treated rats No significant difference in lactate dehydrogenase levels was observed in the liver perfilsate from PFDA-treated and control rats. This suggests that the difference in percent glucose extraction between PFDA-treated and control groups is specifically due to the PFDA treatment and is not attributed to differences in liver viability between groups. Although the exact mechanism for this inhibition in hepatic glucose transport is not known, it is hypothesized that PFDA may have a major impact on membrane structure' flinction which, in turn, may alter glucose transport.