Assessment of Rapid Hepatic Glycogen Synthesis in Humans Using Dynamic 13C Magnetic Resonance Spectroscopy

Abstract

Carbon‐13 magnetic resonance spectroscopy (MRS) following oral intake of 13C‐labeled glucose is the gold standard for imaging glycogen metabolism in humans. However, the temporal resolution of previous studies has been >13 minutes. Here, we describe a high‐sensitivity 13C MRS method for imaging hepatic glycogen synthesis with a temporal resolution of 1 minute or less. Nuclear magnetic resonance spectra were acquired from the liver of 3 healthy volunteers, using a 13C clamshell radiofrequency transmit and paddle‐shaped array receive coils in a 3 Tesla magnetic resonance imaging system. Following a 15‐minute baseline 13C MRS scan of the liver, [1‐13C]‐glucose was ingested and 13C MRS data were acquired for an additional 1‐3 hours. Dynamic change of the hepatic glycogen synthesis level was analyzed by reconstructing the acquired MRS data with temporal resolutions of 30 seconds to 15 minutes. Plasma levels of 13C‐labeled glucose and lactate were measured using gas chromatography–mass spectrometry. While not detected at baseline 13C MRS, [1‐13C]‐labeled α‐glucose and β‐glucose and glycogen peaks accumulated rapidly, beginning as early as ~2 minutes after oral administration of [1‐13C]‐glucose. The [1‐13C]‐glucose signals peaked at ~5 minutes, whereas [1‐13C]‐glycogen peaked at ~25 minutes after [1‐13C]‐glucose ingestion; both signals declined toward baseline levels over the next 1‐3 hours. Plasma levels of 13C‐glucose and 13C‐lactate rose gradually, and approximately 20% of all plasma glucose and 5% of plasma lactate were 13C‐labeled by 2 hours after ingestion. Conclusion: We observed rapid accumulation of hepatic [1‐13C]‐glycogen following orally administered [1‐13C]‐glucose, using a dynamic 13C MRS method with a temporal resolution of 1 minute or less. Commercially available technology allows high temporal resolution studies of glycogen metabolism in the human liver.