Glucose 6-phosphate produced by gluconeogenesis and by glucokinase is equally effective in activating hepatic glycogen synthase.
Glucose 6-phosphate (Glc-6-P) produced in cultured hepatocytes by direct phosphorylation of glucose or by gluconeogenesis from dihydroxyacetone (DHA) was equally effective in activating glycogen synthase (GS). However, glycogen accumulation was higher in hepatocytes incubated with glucose than in those treated with DHA. This difference was attributed to decreased futile cycling through GS and glycogen phosphorylase (GP) in the glucose-treated hepatocytes, owing to the partial inactivation of GP induced by glucose. Our results indicate that the gluconeogenic pathway and the glucokinase-mediated phosphorylation of glucose deliver their common product to the same Glc-6-P pool, which is accessible to liver GS. As observed in the treatment with glucose, incubation of cultured hepatocytes with DHA caused the translocation of GS from a uniform cytoplasmic distribution to the hepatocyte periphery and a similar pattern of glycogen deposition. We hypothesize that Glc-6-P has a major role in glycogen metabolism not only by determining the activation state of GS but also by controlling its subcellular distribution in the hepatocyte.
Gomis
Roger R
RR
Departament de Bioquimica i Biologia Molecular and the Institut de Recerca Biomèdica de Barcelona-Parc Cientific de Barcelona, Universitat de Barcelona, Barcelona E-08028, Spain.
Favre
Cristián
C
García-Rocha
Mar
M
Fernández-Novell
Josep M
JM
Ferrer
Juan C
JC
Guinovart
Joan J
JJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005941:Glucokinase / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000096:biosynthesis*; D006003:Glycogen / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D019298:Glucose-6-Phosphate; D006003:Glycogen; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase; D005941:Glucokinase; D005947:Glucose