Abstract
Administration of p, p'-1, 1, 1-trichloro-2, 2-bis(p-chlorophenyl)ethane (p, p'-DDT) produced marked increases in the activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-diphosphatase and glucose-6-phosphatase in rat kidney cortex. Time-course studies demonstrated that after a single oral dose of p, p'-DDT(600 mg/kg), significant increases in all four key gluconeogenic enzymes occurred at one hour, whereas maximal stimulation of these enzymes was seen four to five hours after insecticide treatment. A similar enhancement (approximately 2-fold at five hours) in the activities of these four gluconeogenic enzymes was observed in hepatic tissue. Dose-response studies revealed that 100 mg/kg of p, p'-DDT was the minimal dose necessary to produce statistically significant increases in the activities of various renal cortex enzymses investigated. Treatment of adrenalectomized rats with p, p'-DDT resulted in stimulation of renal pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase, which was similar to that observed in intact rats. In addition, administration of triamcinolone to p, p'-DDT- treated adrenalectomized rats failed to potentiate the action of this pesticide on kidney gluconeogenic enzymes. Actinomycin D, cycloheximide or ethionine did not affect the basal levels of either of these enzymes, but significantly reduced the DDT-induced increases in various enzyme activities. Daily administration of a small dose of p, p'-DDT (0.5 mg/100 g) for 45 days resulted in significant increases in the activities of various gluconeogenic enzymes in both renal and hepatic tissue. Both p, p'-DDT and o, p'-DDT seemed equally effective in elevating the levels of the four gluconeogenic enzymes in kidney cortex of male and female rats, indicating the lack of a sex difference in the action of the two isomers. Our results suggest that the p, p'-DDT- induced increases in the quartet of renal key, ratelimiting gluconeogenic enzymes are not mediated through glucocorticoid hormones and that new ribonucleic acid and protein synthesis may be involved in the stimulation of the gluconeogenic process in rat kidney after insecticide treatment.
Footnotes
- Received November 1, 1971.
- Accepted January 20, 1972.
- © 1972 by The Williams & Wilkins Co.
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