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Inhibition of lactate glucogneogenesis in rat kidney by dichloroacetate.
- Source :
-
The Biochemical journal [Biochem J] 1978 Mar 15; Vol. 170 (3), pp. 551-60. - Publication Year :
- 1978
-
Abstract
- 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.
- Subjects :
- Adenine Nucleotides metabolism
Animals
Diabetes Mellitus, Experimental metabolism
In Vitro Techniques
Kidney drug effects
Kidney Cortex metabolism
Male
Mitochondria drug effects
Mitochondria metabolism
Pyruvate Dehydrogenase Complex metabolism
Pyruvates metabolism
Rats
Starvation
Acetates pharmacology
Dichloroacetic Acid pharmacology
Gluconeogenesis drug effects
Kidney metabolism
Lactates metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0264-6021
- Volume :
- 170
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 646800
- Full Text :
- https://doi.org/10.1042/bj1700551