The mechanism by which adenosine decreases gluconeogenesis from lactate in isolated rat hepatocytes.
Incubation of hepatocytes from 24 h-starved rats in the presence of 0.5 mM-adenosine decreased gluconeogenesis from lactate, but not from alanine. The inhibition of gluconeogenesis was associated with a stimulation of ketone-body production and an inhibition of pyruvate oxidation. These metabolic changes were suppressed in the presence of iodotubercidin (an inhibitor of adenosine kinase), but were reinforced in the presence of deoxycoformycin (an inhibitor of adenosine deaminase); 2-chloroadenosine induced no change in gluconeogenesis from lactate. These data indicate that the inhibition of gluconeogenesis by adenosine probably results from its conversion into adenine nucleotides. In the presence of lactate or pyruvate, but not with alanine or asparagine, this conversion resulted in a decrease in the [ATP]/[ADP] ratio in both mitochondrial and cytosolic compartments. Adenosine decreased the Pi concentration with all gluconeogenic substrates.
Lavoinne
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A
Groupe de Biochimie et de Physiopathologie Digestive et Nutritionnelle, U.E.R. Médecine et Pharmacie de Rouen, Saint Etienne du Rouvray, France.
Buc
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HA
Claeyssens
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S
Pinosa
M
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Matray
F
F
D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000409:Alanine / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects*; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000096:biosynthesis; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats
D000227:Adenine Nucleotides; D007657:Ketone Bodies; D007773:Lactates; D010710:Phosphates; D011773:Pyruvates; D019344:Lactic Acid; D019289:Pyruvic Acid; D000242:Cyclic AMP; D000241:Adenosine; D000409:Alanine