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

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.

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.

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.

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.