Metabolic Effects of Sodium Dichloroacetate in Normal and Diabetic Dogs

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Abstract
The effects of acute and chronic administration of sodium dichloroacetate (DCA) were studied in the normal and diabetic dog. In the normal dog, a single oral injection of DCA (150 mg/kg) provoked a rapid decrease of the lactate, pyruvate, and triglyceride concentrations and a progressive decrease of blood glucose. These effects lasted longer than 24 h. In the alloxan-diabetic dog deprived of insulin for 72 h, DCA induced a decrease of blood glucose, lactate, and pyruvate concentrations as well as of glucosuria. In these ketotic animals, the plasma lipid compounds and the blood and urinary ketone bodies were not significantly changed by DCA. In the normal dog, the chronic administration of DCA (150 mg/kg daily for 7 days) provoked a decrease in blood glucose, lactate, pyruvate, and oxaloacetate concentrations, which returned to starting values only within 2 to 5 days after the end of the treatment, depending on the compounds studied. A decrease of cholesterol was also noted. During the chronic administration of DCA, blood β-hydroxybutyrate and acetoacetate concentrations strongly increased. When treated with insulin alone, the alloxan-diabetic dogs had a high blood glucose concentration; the blood lactate, pyruvate, and oxaloacetate concentrations did not differ significantly from those of the normal animals, however. In these diabetic dogs, the lipid compounds and, particularly, the ketone compounds were increased. The addition of DCA (75 mg/kg daily for 7 days) provoked a drop in blood lactate, pyruvate, and oxaloacetate levels, and a reduction of blood glucose and plasma cholesterol, triglyceride, and total lipids was also noted. Blood β-hydroxybutyrate and acetoacetate concentrations, which were already high at the start, were not affected when DCA was associated to insulin. This addition of DCA provoked a rapid and marked reduction in glucosuria, which was concomitant with an increase in urinary β-hydroxybutyrate and acetone.