Interactions between glucose and ketone body use by developing brain

Alexander L. Miller, Colleen A. Kiney, David H. Corddry, Donna M. Staton

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The effects of ketonemia on brain carbohydrate metabolism of 20-day-old rats breathing air or 20% CO2 were studied. Intraperitoneal administration of sodium dl-β-hydroxybutyrate (8-10 mmol/kg) significantly reduced rates of glucose utilization by brains of both groups, as determined with [2-14C]glucose and [3H]deoxyglucose as tracers. The greater decrease found with [2-14C]glucose indicated that loss of a 14C-labeled intermediate from brain also occurred during ketonemia. Other investigators have observed release of lactate from brain into blood during ketonemia. It is likely that the loss of 14C was by this route. The decrease in rate of glucose utilization produced by ketonemia was additive with the decrease produced by hypercapnia. Changes in brain metabolite concentrations with ketonemia included increases in glucose, glucose 6-phosphate, pyruvate, citrate, α-ketoglutarate, malate, and glutamate. With the combination of ketonemia and hypercapnia there were further increases in brain glucose and glucose 6-phosphate concentrations, while the levels of the other metabolites fell to about the same or to a lesser extent as occurred with hypercapnia alone. These observations, coupled with those on rates of glucose utilization, support the following conclusions: (1) acute ketonemia diminished flux through the hexokinase, phosphofructokinase, and pyruvate dehydrogenase reactions, but total influx of substrates into the Krebs cycle temporarily exceeded CO2 evolution, leading to increased concentrations of cycle intermediates and glutamate; (2) hypercapnia superimposed on ketonemia had an additive inhibitory effect on phosphofructokinase activity; (3) during combined hypercapnia and ketonemia, there did not appear to be an adaptive increase in use of β-hydroxybutyrate by brain to compensate for the CO2-produced reduction in glucose use.

Original languageEnglish (US)
Pages (from-to)443-450
Number of pages8
JournalDevelopmental Brain Research
Issue number4
StatePublished - Aug 1982


  • brain
  • development
  • glucose
  • hypercapnia
  • ketone bodies
  • metabolism

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology


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