INVESTIGATION OF THE MECHANISM OF GLYCOGEN REBOUND IN THE LIVER OF 72-HOUR FASTED RATS

We have investigated the mechanism of the rebound of glycogen stores i n the liver of 72-h fasted rats. The liver of 72- and 96-h fasted rats contains significant amounts of glycogen (about 5 mg/g, wet weight) a s compared to the liver of 24- and 48-h fasted rats, which contains le ss than 2 mg of glycogen/g of liver, wet weight. Rebound of glycogen d oes not involve glycogen synthase activation or glycogen phosphorylase inhibition. It could be dependent on the concentration of the precurs or substrate of glycogenesis, i.e. glucose 6-phosphate (Glc-6-P), whic h is higher by about 45% in the liver of 72- and 96-h fasted rats than in the liver of 48-h fasted rats. The 72-h increase of Glc-6-P compar ed with the 48-h values could not be explained either by late modifica tions of the total activities of glucokinase, hexokinases, Glc-6-P deh ydrogenase, and glucose-6-phosphatase (Glc-6-Pase) or by changes in pl asma glucose and insulin/glucagon ratio. In agreement with the fact th at total glucose output tends to decrease upon prolonged fasting, the increase of Glc-6-P concentration in the liver of 72-h fasted rats sug gests the involvement of a metabolite inhibition of Glc-6-Pase. The in crease of the cy-ketoglutarate concentration in the 72- and 96-h faste d liver with regard to the 48-h fasted liver (about three times) might account for such an inhibition since we show here that Glc-6-Pase is inhibited in vitro in the presence of relevant concentrations of alpha -ketoglutarate, Glc-6-P, and Mg2+ ions.