Simultaneous in vivo monitoring of hepatic glucose and glucose-B-phosphateby C-13-NMR spectroscopy

Hepatic glucose-6-phosphate (G6P) was monitored non-invasively in rat liver by in vivo C-13 NMR spectroscopy after infusion of [1-C-13] glucose. The p hosphorylation of glucose to G6P yields small but characteristic displaceme nts for all of its C-13-NMR resonances relative to those of glucose. It is demonstrated that in vivo C-13-NMR spectroscopy at 7 Tesla provides the spe ctral sensitivity and resolution to detect hepatic G6P present at sub-milli molar concentration as partially resolved low-field shoulders of the glucos e C1 resonances at 96.86 ppm (C1 beta) and 93.02 ppm (C1 alpha). Upon C-13- labeling, the intracellular conversion of [1-C-13] glucose to [1-C-13] G6P could be monitored, which allowed the hepatic glucose-G6P substrate cycle t o be assessed in situ. The close correlation found for the C-13 labeling pa tterns of glucose and G6P supports the concept of an active substrate cycle whose rate exceeds that of net hepatic glucose metabolism. High-resolution C-13-NMR spectroscopy and biochemical analyses of tissue biopsies collecte d at the end of the experiments confirmed qualitatively the findings obtain ed in vivo. (C) 2000 Wiley-Liss, Inc.