Measurement of glucose recycling and liver glycogen synthesis in mice using doubly labeled substrates

Tracer experiments have been carried out using gorging and nibbling mice to study several related aspects of carbohydrate metabolism: 1) inhibition of gluconeogenesis shortly after animals ingest a glucose-rich meal; 2) the extent to which dietary glucose carbon is recycled by way of 3C compounds after dietary glucose is absorbed; and 3) recycling of glucose by exchange between free and a hypothetical, "bound" glucose pool. Fasted, gorging mice were allowed to eat 120 mg [U-14C,6-T]glucose (58% glucose diet) in 4 min. Plasma glucose-C specific activity rapidly reached that of the dietary glucose-C. Superficially, this suggested nearly complete inhibition of hepatic gluconeogenesis. However, plasma [6-T]glucose, glycogen-[14C, 3H]glucose analyses, and [14C]-glycerol conversion to glucose showed that hepatic gluconeogenesis continued during alimentary hyperglycemia. Half of liver glycogen seemed to be formed from a hepatic G-6-P pool that was never labeled. Indirect kinetic evidence of a large, bound exchangeable glucose pool was presented. Since no direct evidence of such a pool has been obtained, the possibility is raised that a serious artifact of the tracer technique exists or else some unconventional model of carbohydrate metabolism is required to explain our data.