Acute effects of dichloroacetate in the depancreatized dog: glucose synthesis and turnover.

Blood glucose turnover (entry and removal rates) and the rate of recycling of radiolabelled glucose carbon into newly synthesized blood glucose have been evaluated before and acutely after the administration of dichloroacetate to depancreatized dogs. Blood glucose concentration began to decline immediately after dichloroacetate administration and fell to new steady state levels within 1.5-3 h. Analysis of blood glucose kinetics during the decline demonstrated a 52% (average) reduction in the rate of hepatic glucose supply. Glucose supply remained reduced over the duration of these studies (3-4.5 h). Glucose turnover in the steady state following dichloroacetate administration averaged 62% of pretreatment values. Cori cycle activity was depressed by 63% after dichloroacetate administration. The results of these studies are consistent with the hypothesis that a major mechanism underlying the hypoglycaemic action of this drug is the inhibition of glucose synthesis.