Noninvasive observation of hepatic glycogen formation in man by 13C MRS after oral and intravenous glucose administration

Abstract

The formation of glycogen in the liver of normal volunteers was followed noninvasively with 13C magnetic resonance spectroscopy (MRS) under two different conditions: a) intravenous infusion of [1-13C]glucose under hyperglycemic and hyperinsulinemic clamp conditions, and b) oral intake of glucose in the form of a bolus. For the intravenous infusion, [1-13C]glucose with an enrichment level of 99% was employed. The C1 signals of alpha- and beta-glucose could be detected in the human liver already after an infusion period of 8 min. However, an increase in the glycogen signal was observed only after a prolonged infusion of about 60 min. Changes in the glycogen signal correlated well with the time course of insulin and glucagon during the measurement. Experiments showed also that liver glycogen formation in man can be followed noninvasively by 13C-MRS using nonlabeled glucose or [1-13C]glucose with a low level of enrichment (6.6%). The use of nonlabeled glucose may therefore simplify the quantitation of net liver glycogen synthesis since it can be based directly on changes in the natural abundance 13C MRS glycogen signal, avoiding label dilution through the various metabolic pathways of glucose. The glucose uptake, estimated from the increase in the glycogen signal, was consistent with findings from more complex and invasive studies of glucose uptake in the liver. The average liver glycogen concentration in 12 h overnight fasted volunteers (n = 18) without any special dietary preparation was assessed to be 229 +/- 34 mM (minimum = 160 mM; maximum = 274 mM).