Human liver glycogen metabolism assessed with a 13C‐enriched diet and a 13CO2 breath test

BACKGROUND: Adequate liver glycogen stores to maintain hepatic glucose output by glycogenolysis in the post-absorptive state are essential to prevent protein loss through gluconeogenesis. There are no simple techniques to monitor liver glycogen use. METHODS: In this study, we labelled liver glycogen with naturally 13C-enriched carbohydrate and measured the pattern of 13CO2 excretion and the post-prandial time during which oxidation of 13C-labelled liver glycogen was demonstrable by 13CO2 enrichment in breath. Two experiments were performed in 24 healthy volunteers. RESULTS: In the first experiment we observed that breath 13CO2 enrichment returned to baseline values at 20.3 (SD 2.3, n = 12) hours post-prandially, indicating exhaustion of the 13C-labelled liver glycogen at that time. In a second experiment, breath 13CO2 enrichment in the early hours of the post-prandial phase was studied. After a steep decline, which started 2-4 h after the last meal, the 13CO2 enrichment reached a plateau phase 6 h post-prandially. This plateau phase lasted for about 6-8 h, suggesting steady-state glycogenolysis during this period. The plateau phase was followed by a further decline in 13CO2 excretion, suggesting a gradually diminishing contribution of 13C-labelled liver glycogen to substrate oxidation. CONCLUSION: It is possible to label liver glycogen with a diet of naturally 13C-enriched carbohydrate. The oxidation of the labelled liver glycogen can be monitored by measuring 13C-enrichment in breath CO2.