The interaction of carbaryl with the metabolism of isolated hepatocytes: II. Effect on gluconeogenesis.
The effects of 1-naphthyl-N-methylcarbamate (carbaryl) upon glucose production from several precursors (lactate, glycerol, alanine, fructose and pyruvate) and on activities of gluconeogenic enzymes (glucose-6-phosphatase, lactate dehydrogenase and aspartate aminotransferase) in isolated rat hepatocytes was studied. The results show that carbaryl inhibits lactate-gluconeogenesis at all concentrations of substrate studied. Gluconeogenesis from 10 mM fructose or 10 mM pyruvate or 10 mM alanine is also inhibited by carbaryl 1 mM. However, glycerol-gluconeogenesis is unaffected. Concentrations of carbaryl at 0.01 and 0.1 mM did not significantly modify lactic dehydrogenase activity, but at 1.0 mM this activity was reduced by 38% in relation to the dimethylsulphoxide-treated group. The synthetic activity of glucose-6-phosphatase is enhanced by carbaryl, but the increase is only significant for 1 mM carbaryl. In the study of aspartate aminotransferase activities two fractions, cytoplasmic and mitochondrial, are differentiated; and, it is observed that both fractions are inhibited by 0.1 and 1.0 mM carbaryl. The results indicate that carbaryl produces major decreases of the glucose production by hepatic cells, and suggest that the carbaryl-induced hyperglycemia in the fasted animal would be due to deficiencies in the peripheral utilization of the glucose.
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D012721:Carbaryl / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D005952:Glucose-6-Phosphatase; D012721:Carbaryl; D004121:Dimethyl Sulfoxide