The Metabolic Effects of Sodium Dichloroacetate in the Suckling Newborn Rat

Subcutaneous injection of sodium dichloroacetate (1 microgram/ g body wt every 3 h) in suckling newborn rats caused in 6 h a fall of 2.5 mmol/l in blood glucose concentrations, and a rise of 2.4 mmol/l in total blood ketone body levels, but no change in the high levels of plasma non esterified fatty acids. Glucose utilization, measured after intraperitoneal injection of D-glucose (2 microgram/g body wt), was not increased in newborns injected with dichloroacetate. The hypoglycaemia resulted from a decrease in gluconeogenic rate, secondarily to a lowering effect of dichloroacetate on blood levels of lactate, pyruvate and alanine. The hypoglycaemia induced by dichloroacetate was completely reversed by injecting newborn rats with a mixture of gluconeogenic precursors (lactate, pyruvate and alanine). It is concluded that the high rate of gluconeogenesis observed in suckling newborn rats in sustained by an increased release of lactate and, to a much smaller extent of pyruvate and alanine, by peripheral tissues. This probably resulted from the low pyruvate dehydrogenase activity found in peripheral tissues of the newborn rat. The hyperketonaemia induced by dichloroacetate could result from an increased ketogenesis and/or a decreased ketone body utilization.