Effect of Acute Hypoglycemia on Human Cerebral Glucose Metabolism Measured by 13C Magnetic Resonance Spectroscopy

  1. Arend Heerschap1
  1. 1Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
  2. 2Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
  3. 3Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
  4. 4Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota
  1. Corresponding author: Kim C.C. van de Ven, k.vandeven{at}


OBJECTIVE To investigate the effect of acute insulin-induced hypoglycemia on cerebral glucose metabolism in healthy humans, measured by 13C magnetic resonance spectroscopy (MRS).

RESEARCH DESIGN AND METHODS Hyperinsulinemic glucose clamps were performed at plasma glucose levels of 5 mmol/L (euglycemia) or 3 mmol/L (hypoglycemia) in random order in eight healthy subjects (four women) on two occasions, separated by at least 3 weeks. Enriched [1-13C]glucose 20% w/w was used for the clamps to maintain stable plasma glucose labeling. The levels of the 13C-labeled glucose metabolites glutamate C4 and C3 were measured over time in the occipital cortex during the clamp by continuous 13C MRS in a 3T magnetic resonance scanner. Time courses of glutamate C4 and C3 labeling were fitted using a one-compartment model to calculate metabolic rates in the brain.

RESULTS Plasma glucose 13C isotopic enrichment was stable at 35.1 ± 1.8% during euglycemia and at 30.2 ± 5.5% during hypoglycemia. Hypoglycemia stimulated release of counterregulatory hormones (all P < 0.05) and tended to increase plasma lactate levels (P = 0.07). After correction for the ambient 13C enrichment values, label incorporation into glucose metabolites was virtually identical under both glycemic conditions. Calculated tricarboxylic acid cycle rates (VTCA) were 0.48 ± 0.03 μmol/g/min during euglycemia and 0.43 ± 0.08 μmol/g/min during hypoglycemia (P = 0.42).

CONCLUSIONS These results indicate that acute moderate hypoglycemia does not affect fluxes through the main pathways of glucose metabolism in the brain of healthy nondiabetic subjects.


  • Received November 16, 2010.
  • Accepted February 28, 2011.

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