Glucose starvation results in UDP-glucose deficiency and inactivation of glycogen synthase.
The effects of glucose starvation on glycogen synthase (GS) activity and protein expression were investigated. Fibroblasts were cultured in medium supplemented with either glucose or pyruvate. Pyruvate-cultured cells exhibited UDP-glucose contents that amounted to approximately 10% of those in cells cultured with glucose. GS activity, protein and mRNA amounts in pyruvate-cultured cells were decreased to approximately 35, 60, and 60%, respectively, of values in glucose-cultured cells. Incubation of extracts from glucose-cultured cells with radioactive UDP-glucose resulted in substantial binding of ligand to immunoprecipitated GS. However, binding in immunoprecipitates from pyruvate-cultured cells was decreased to approximately 25% of values in glucose-cultured cells. These data indicate that glucose starvation and the subsequent depletion of UDP-glucose result in: (1) inactivation of GS, owing to a decrease in its ability to bind UDP-glucose, and (2) decreased amount of GS protein, owing to a decrease in the levels of GS mRNA.
Higuita
Juan Carlos
JC
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm S-171 77, Sweden.
Thelestam
Monica
M
Katz
Abram
A
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation; D004791:Enzyme Inhibitors; D005347:Fibroblasts / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency*; D006006:Glycogen Synthase / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D013217:Starvation / Q000378:metabolism; D014532:Uridine Diphosphate Glucose / Q000172:deficiency*
D004791:Enzyme Inhibitors; D006006:Glycogen Synthase; D005947:Glucose; D014532:Uridine Diphosphate Glucose