title: Effect of acute hypoglycemia on human cerebral glucose metabolism measured by ¹³C magnetic resonance spectroscopy.
abstract: OBJECTIVE
  To investigate the effect of acute insulin-induced hypoglycemia on cerebral glucose metabolism in healthy humans, measured by (13)C magnetic resonance spectroscopy (MRS).
  
  
  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-(13)C]glucose 20% w/w was used for the clamps to maintain stable plasma glucose labeling. The levels of the (13)C-labeled glucose metabolites glutamate C4 and C3 were measured over time in the occipital cortex during the clamp by continuous (13)C 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 (13)C 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 (13)C enrichment values, label incorporation into glucose metabolites was virtually identical under both glycemic conditions. Calculated tricarboxylic acid cycle rates (V(TCA)) 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.
authors.affiliation: Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. k.vandeven@rad.umcn.nl
authors.forename: Kim C C
authors.initials: KC
authors.lastname: van de Ven
authors.forename: Bastiaan E
authors.initials: BE
authors.lastname: de Galan
authors.forename: Marinette
authors.initials: M
authors.lastname: van der Graaf
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shestov
authors.forename: Pierre-Gilles
authors.initials: PG
authors.lastname: Henry
authors.forename: Cees J J
authors.initials: CJ
authors.lastname: Tack
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
mesh_terms: D000328:Adult; D054022:Cerebrum / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008954:Models, Biological
chemical_list: D005947:Glucose