To estimate the relative contribution of the indirect pathway to liver glycogen formation in humans, different experimental approaches have been used. Although the estimates vary, it appears that in overnight fasted humans approximately 50% of liver glycogen is derived from the direct pathway following a glucose load and that the direct pathway increases to approximately 70% after the first meal of the day. While the source of the gluconeogenic substrates is still unknown, the animal data suggest that the liver itself may be an important source.