The metabolic effects of sodium dichloroacetate in the starved rat

Abstract

Sodium dichloroacetate (300 mg/kg body wt. per h) was infused in 24 hr starved rats for 4 hr. Blood glucose decreased significantly, an effect that had previously only been noted in diabetic animals. Plasma insulin concentration decreased by 63% blood lactate and pyruvate concentrations decreased by 50 and 33%, whereas concentrations of 3 hydroxybutyrate and acetoacetate increased by 81 and 73% respectively. Livers were freeze clamped at the end of the 4 hr infusion. There were significant decreases in hepatic [glucose], [glucose 6 phosphate], [2 phosphoglycerate], the [lactate]/[pyruvate] ratio, [citrate] and [malate], and also [alanine], [glutamate] and [glutamine], suggesting a diminished supply of gluconeogenic substrates. Animals subjected to a functional hepatectomy at the end of 2 hr infusions showed no difference in blood glucose disappearance but a highly significant decrease in the rate of accumulation of lactate, pyruvate, glycerol and alanine, compared with control animals. Dichloroacetate decreased ketonebody clearance. After functional hepatectomy an increase in glutamine accumulation appeared to compensate for the decrease in alanine accumulation. It is concluded that dichloroacetate causes hypoglycaemia by decreasing the net release of gluconeogenic precursors from extrahepatic tissues while inhibiting peripheral ketone body uptake.