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

OBJECT WE-To investigate the effect of acute insulin-induced hypoglycemia on cerebral glucose metabolism in healthy humans, measured by C-13 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-C-13]glucose 20% w/w was used for the clamps to maintain stable plasma glucose labeling. The levels of the C-13-labeled glucose metabolites glutamate C4 and C3 were measured over time in the occipital cortex during the clamp by continuous C-13 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 C-13 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 C-13 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 mu mol/g/min during euglycemia and 0.43 +/- 0.08 mu mol/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. Diabetes 60:1467-1473, 2011