Inhibition of lactate glucogneogenesis in rat kidney by dichloroacetate.
1. Sodium dichloroacetate (1mM) inhibited glucose production from L-lactate in kidney-cortex slices from fed, starved or alloxan-diabetic rates. In general gluconeogenesis from other substrates was no inhibited. 2. Sodium dichloracetate inhibited glucose production from L-lactate but no from pyruvate in perfused isolated kidneys from normal or alloxan-diabetic rats. 3. Sodium dichloroacetate is an inhibitor of the pyruvate dehydrogenase kinase reaction and it effected conversion of pyruvate dehydrogenase into its its active (dephosphorylated) form in kidney in vivo. In general, pyruvate dehydrogenase was mainly in the active form in kidneys perfused or incubated with L-lactate and the inhibitory effect of dichloroacetate on glucose production was not dependent on activation of pyruvate dehydrogenase. 4. Balance data from kidney slices showed that dichloroacetate inhibits lactate uptake, glucose and pyruvate production from lactate, but no oxidation of lactate. 5. The mechanism of this effect of dichloroactetate on glucose production from lactate has not been fully defined, but evidence suggests that it may involve a fall in tissue pyruvate concentration and inhibition of pyruvate carboxylation.
D000085:Acetates / Q000494:pharmacology*; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007773:Lactates / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D013217:Starvation
D000085:Acetates; D000227:Adenine Nucleotides; D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D003999:Dichloroacetic Acid