Glucose metabolism is central to many obesity disorders. While techniques for monitoring circulating blood glucose levels are easier than ever, such measurements do not provide insight into how blood glucose is actually used by the tissues in the body.
We employed an experimental approach called glucose oxidation testing (GOT) to quantify glucose oxidation in real time. Laboratory mice (Mus musculus) were given IP injections of trace amounts of 13C-U-glucose (75-600μg) after which we measured both the rates of CO2 production (VCO2) and the isotopic enrichment of the breath (13CO2) at 1Hz frequency using the new Sable Systems Stable Isotope Gas Analyzer. We conducted dose response (75-600μg) trials at 22°C and fixed-dose (300μg) trials at three temperatures (10, 22, and 30°C) and different nutritional states (fed vs. 24h-fasted).
The 13CO2 increased within 90-seconds and peak values occurred approximately 15-30 min. later. The dose responses were isometric across the range examined suggesting no mass action effects of the tracer. In fed mice we observed lower 13CO2, but the differences were counterbalanced by the increased VCO2 caused by cold temperatures; thus, temperature had no effect on net glucose tracer oxidation rates. Nutritional stress (fasting) generally caused attenuated and protracted oxidation kinetics resulting in a 40% reduction in tracer oxidation in mice exposed to 22°C and 30°C.
Collectively, this study demonstrates how GOT can be used to characterize small and rapid changes in glucose disposal, and we expect that this approach will be useful to investigate differences in glucose oxidation in obesity and diabetes studies in human and clinical models.