Quantitation of glycogen/glucose-1-P cycling in liver

A method is introduced for quantitating cycling between hepatic glycogen and glucose-1-P in humans. It depends on the administration of trace [2-3H,6-14C]galactose, a glucose load, and acetaminophen. The ratio of 3H to 14C in the glucuronide of the acetaminophen excreted in urine to that in the administered galactose provides the measure of the fraction of glycogen synthesized that is synthesized from glucose-1-P formed from glycogen. The quantity of glucose-1-P formed from glycogen that is not reconverted to glycogen is not measured. It is assumed that the glucuronide samples the UDP-glucose pool in liver from which glycogen is formed, the last glucosyl units formed from UDP-glucose in glycogen synthesis are the first broken down, and the equilibration of [2-3H]glucose-1-P with fructose-6-P is rapid relative to its conversion to UDP-glucose. During a 5-hour period, while three normal subjects and three non-insulin-dependent diabetics, who had fasted overnight, were infused with 4 mg/kg/min of glucose, the rate of glycogen breakdown, as measured using the method, was only a small percentage of the rate of glycogen synthesis.