Metabolism of adenosine through adenosine kinase inhibits gluconeogenesis in isolated rat hepatocytes.
In isolated hepatocytes from fasted rats, 0.5 mM adenosine inhibited gluconeogenesis from glutamine, lactate and pyruvate. This inhibition was due to adenosine conversion through adenosine kinase. An increase in ketone body release was only observed in the presence of lactate or pyruvate, and the two phenomena (i.e. inhibition of gluconeogenesis and increased ketone-body release) were linked. With alanine, dihydroxyacetone or serine as substrates, adenosine did not change gluconeogenesis; however, its conversion through adenosine kinase also inhibited gluconeogenesis. With asparagine as substrate, 0.5 mM adenosine increased gluconeogenesis; this increase was due to adenosine conversion through adenosine deaminase. However, adenosine conversion through adenosine kinase inhibited gluconeogenesis from asparagine. Thus, whatever the substrate used, adenosine conversion through adenosine kinase inhibited gluconeogenesis. The inhibitory effect of adenosine on gluconeogenesis cannot be related to the decrease in Pi concentration and to the increase in ATP pool. Beside its effect on gluconeogenesis, adenosine inhibited ketogenesis measured without added substrate; adenosine conversion through adenosine kinase was also involved in the inhibition of ketogenesis.
Lavoinne
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Groupe de Biochimie et Physiopathologie Digestive et Nutritionelle, Unité de Formation et de Recherche Médecine et Pharmacie de Rouen, France.
Claeyssens
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Chedeville
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D000241:Adenosine / Q000494:pharmacology*; D000248:Adenosine Kinase / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005215:Fasting / Q000378:metabolism; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects*; D005973:Glutamine / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007657:Ketone Bodies; D007773:Lactates; D011773:Pyruvates; D005973:Glutamine; D010770:Phosphotransferases; D000248:Adenosine Kinase; D000241:Adenosine