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 in 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) as compared to the liver of 24- and 48-h fasted rats, which contains less than 2 mg of glycogen/g of liver, wet weight. Rebound of glycogen does not involve glycogen synthase activation or glycogen phosphorylase inhibition. It could be dependent on the concentration of the precursor substrate of glycogenesis, i.e. glucose 6-phosphate (Glc-6-P), which 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 compared with the 48-h values could not be explained either by late modifications of the total activities of glucokinase, hexokinases, Glc-6-P dehydrogenase, and glucose-6-phosphatase (Glc-6-Pase) or by changes in plasma glucose and insulin/glucagon ratio. In agreement with the fact that total glucose output tends to decrease upon prolonged fasting, the increase of Glc-6-P concentration in the liver of 72-h fasted rats suggests the involvement of a metabolite inhibition of Glc-6-Pase. The increase of the alpha-ketoglutarate concentration in the 72- and 96-h fasted 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.
Minassian
C
C
INSERM, Unité 197, Faculté de Médecine Alexis Carrel, Lyon, France.
Ajzannay
A
A
Riou
J P
JP
Mithieux
G
G
D000818:Animals; D005215:Fasting / Q000378:metabolism*; D005941:Glucokinase / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D019298:Glucose-6-Phosphate; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006706:Homeostasis; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005958:Glucosephosphates; D008112:Liver Glycogen; D019298:Glucose-6-Phosphate; D005954:Glucosephosphate Dehydrogenase; D006005:Phosphorylases; D006006:Glycogen Synthase; D006593:Hexokinase; D005941:Glucokinase; D005952:Glucose-6-Phosphatase