Hepatocyte DNA replication: effect of nutrients and intermediary metabolites.
Isolated adult rat liver parenchymal cells maintained in serum-free medium are stimulated by insulin and epidermal growth factor (EGF) to undergo DNA synthesis. Pyruvate, lactate, and, to a lesser extent, several other intermediary metabolites strikingly enhance DNA synthesis both under serum-free culture conditions and in the presence of dialyzed rat serum. High concentrations (2-50 mM) of these low-molecular-weight metabolites are necessary to produce optimal stimulation. Both alanine (greater than 2 mM) and glutamine (greater than 4 mM) are inhibitory under similar conditions. Glucose, although not required for hepatocyte maintenance or stimulation in the presence of insulin and EGF, acts synergistically with pyruvate to enhance DNA synthesis in a complete mixture.
D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D004261:DNA Replication / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D013936:Thymidine / Q000378:metabolism
D003470:Culture Media; D007328:Insulin; D011773:Pyruvates; D004815:Epidermal Growth Factor; D019289:Pyruvic Acid; D005947:Glucose; D013936:Thymidine