Simultaneous in vivo monitoring of hepatic glucose and glucose-6-phosphate by ¹³C-NMR spectroscopy^†

Hepatic glucose-6-phosphate (G6P) was monitored non-invasively in rat liver by in vivo ¹³C NMR spectroscopy after infusion of [1-¹³C] glucose. The phosphorylation of glucose to G6P yields small but characteristic displacements for all of its ¹³C-NMR resonances relative to those of glucose. It is demonstrated that in vivo ¹³C-NMR spectroscopy at 7 Tesla provides the spectral sensitivity and resolution to detect hepatic G6P present at sub-millimolar concentration as partially resolved low-field shoulders of the glucose C1 resonances at 96.86 ppm (C1β) and 93.02 ppm (C1α). Upon ¹³C-labeling, the intracellular conversion of [1-¹³C] glucose to [1-¹³C] G6P could be monitored, which allowed the hepatic glucose-G6P substrate cycle to be assessed in situ. The close correlation found for the ¹³C labeling patterns of glucose and G6P supports the concept of an active substrate cycle whose rate exceeds that of net hepatic glucose metabolism. High-resolution ¹³C-NMR spectroscopy and biochemical analyses of tissue biopsies collected at the end of the experiments confirmed qualitatively the findings obtained in vivo. Magn Reson Med 44:556–562, 2000. © 2000 Wiley-Liss, Inc.