Resolving futile glucose cycling and glycogenolytic contributions to plasma glucose levels following a glucose load.

PURPOSE: After a glucose load, futile glucose/glucose-6-phosphate (G6P) cycling (FGC) generates [2-(2) H]glucose from (2)H(2)O thereby mimicking a paradoxical glycogenolytic contribution to plasma glucose levels. Contributions of load and G6P derived from gluconeogenesis, FGC, and glycogenolysis to plasma glucose levels need resolution. A simple methodology is proposed integrating the administration of (2)H(2)O with a glucose load containing [1-(2)H, 1-(13)C]glucose and [2-(2)H, 2-(13)C]glucose.
METHODS: Mice fasted for 6 (n = 7) or 24 h (n = 5) were intraperitoneally injected with 2 mg/g 10% enriched glucose in 35 µL/g (2)H(2)O. Plasma glucose enrichment was analyzed by (2)H NMR after 30 min.
RESULTS: For 6-h fasted mice, 12.3 ± 1.5% of plasma glucose was pre-existing, 44.3 ± 2.7% was load derived, and 43.4 ± 1.8% G6P derived. G6P origins were 26.0 ± 2.0% gluconeogenesis, 10.9 ± 2.6% FGC, and 6.5 ± 3.4% glycogenolysis. For 24-h fasted mice, 18.2 ± 8.5% was pre-existing, 41.1 ± 5.0 % was load derived, and 40.8 ± 4.3% G6P derived. G6P origins were 27.1 ± 3.3% gluconeogenesis, 13.1 ± 2.8% FGC, and 0.6 ± 2.4% glycogenolysis.
CONCLUSION: After a glucose load, glycogenolytic contribution to plasma glucose was negligible, whereas FGC was significant for both 6- and 24-h fasted mice.