Coordinated regulation of hepatic glycogen formation in perfused rat liver by glucose and lactate

Lactate has been found to enhance the formation of glycogen from both glucose and lactate as substrate (Z. Zhang and J. Radziuk. Biochem. J. 280: 415-419, 1991). To evaluate the relative importance of its role as substrate and regulatory factor, a dual dose-response evaluation was done by adding variable amounts of glucose and lactate to the medium in a recirculating perfused rat liver preparation. Nine groups of perfusions were performed utilizing three different levels of carbon infusion into the system: 0.25, 1.0, and 2.0 mg/min. These levels of carbon infusion were further subdivided into different relative amounts of glucose and lactate. Lactate uptake by the perfused liver was linearly related with net glucose output, regardless of the glucose concentrations. In contrast to this, the effect of lactate uptake on the rate of glycogen synthesis is saturable. Moreover, the rate of glycogen formation at which this saturation occurs is dependent only on the mean perfusate glucose concentration. The highest amount of glycogen formed in a 2-h period was 50 +/- 7 mg and the lowest 3.4 +/- 0.3 mg. A family of dose-response curves was generated describing this dual dependence of glycogen formation (both direct and gluconeogenetic pathways) on lactate and glucose.