The effect of 48 hr glucose administration on the hepatic P450 system

The administration of glucose for 48 hrs to mice resulted in a shift of the dose response curve of pentobarbital, an indication that glucose administration significantly sensitized the animals to the effects of the drug. Glucose administration produced a reduction in the catalytic activity of hepatic microsomal P-450 as measured by the in vitro conversion of p-Nitroanisole to p-Nitrophenol.;The administration of glucose to rats for 48 hrs resulted in prolonged anesthesia after the administration of pentobarbital. The spectral binding of hexobarbital and methadone to hepatic microsomal P-450 was found to be significantly reduced following glucose administration. The changes in spectral binding were observed in the absence of any significant change in the microsomal P-450 content. The changes in the spectral binding of hexobarbital and methadone to P-450 in glucose treated animals might suggest that glucose administration is causing a qualitative or conformational change in hepatic microsomal P-450 enzymes. Glucose administration resulted in an increase in the cytosolic protein content which may possibly indicate that glucose is inducing enzymes responsible for its metabolism and/or the synthesis of lipids from glucose.;Glucose treatment produced a decrease in hepatic glycogen content and an increase in total microsomal lipid, phospholipid, and fatty acid content. Specific fatty acid and phospholipid contents were also measured following glucose administration. The results showed that there was an increase in microsomal palmitic, palmitoleic, stearic and oleic acids as well as the phospholipids phosphatidylcholine and phosphatidylethanolamine. Changes in lipid content and specific fatty acid content have been shown to be associated with changes in microsomal P-450 activity and the binding of various substrates to P-450. The data reported in these studies suggest that glucose administration was associated with quantitative alterations in specific microsomal lipid content and that the lipid changes could have influenced the activity of microsomal P-450 and the binding of drug substrates to P-450.