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

摘要

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). Research design and methods-hyperinsulihemic 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]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 counterregu-latory 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 ± 0.08μmol/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