Importance of ammonium ions in regulating hepatic glutamine synthesis during fasting

E. Cersosimo, P. Williams, R. Geer, T. Lairmore, F. Ghishan, N. N. Abumrad

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11 Scopus citations


Four-day fasting in the conscious dog is associated with enhanced ammoniagenesis in both the gut and kidneys and a switch in the hepatic glutamine balance from net uptake to that of net production. In the present study we examined the role that the rise in portal venous ammonium ions plays in regulating nitrogen metabolism in vivo. Three groups of 18- to 24-h fasted conscious dogs with catheters surgically implanted in the femoral artery and in the hepatic, portal, and renal veins for 17-21 days were studied. On the day of the study, one group (n = 6) received intraportal ammonium acetate at 3.0 μmol·kg-1·min-1 intended to result in portal venous ammonium ion levels slightly above those seen in the 4-day fasted dog. Another group (n = 5) received an equimolar infusion of sodium acetate, and a third group (n = 6) received saline (0.9%) and acted as controls. Organ balances across the liver, extrahepatic splanchnic tissues (gut), and kidneys were estimated by the arteriovenous differences multiplied by blood flows. All of the load of ammonium acetate infused intraportally was taken up by the liver. As a result there was an immediate switch in hepatic glutamine balance from that of net uptake to net production similar to that seen in the 4-day fasted dog. Simultaneously, net hepatic production or urea nitrogen doubled. These occurred with no change in acid-base balance or no change in circulating arterial or portal venous levels of insulin and glucagon. The data indicate that the load of portal ammonium ions acts as an important signal to trigger the liver to produce glutamine, a condition seen with 4 days of fasting and with acute and chronic metabolic acidosis.

Original languageEnglish (US)
Pages (from-to)20/4
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number4
StatePublished - 1989

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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