title: Glucose starvation reduces IGF-I mRNA in tumor cells: evidence for an effect on mRNA stability.
abstract: The purpose of this study was to characterize the mechanisms by which glucose regulates IGF-I gene expression in rat C6 glioma cells and in rat GH3 pituitary adenoma cells. Glucose starvation for periods of 12 to 48 h decreased IGF-I mRNA levels. In contrast, there was no stimulation of IGF-I mRNA by medium glucose between 1 and 25 mM over a 24-h period. Studies with hexoses and glycolytic metabolites suggested that glucose metabolism was required to maintain IGF-I mRNA. Glucose starvation lowered IGF-I mRNA half-life in both C6 and GH3 cells. Protein synthesis inhibition lowered IGF-I mRNA by about 20% in glucose-fed C6 and GH3 cells, while potently increasing IGF-I mRNA in glucose-starved C6 cells and not altering IGF-I mRNA in glucose-starved GH3 cells. Our results suggest that in these tumor cells, IGF-I mRNA stability is reduced by glucose starvation, secondary to a deficiency in intracellular glucose metabolism. Ongoing protein synthesis is not required for this mRNA de-stabilizing effect in GH3 cells. Rather, in glucose-starved C6 cells, decreased IGF-I mRNA stability may result from the action of a labile protein.
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, 7730 Floyd Curl Drive, San Antonio, Texas 78284-7760, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: M L
authors.initials: ML
authors.lastname: Adamo
mesh_terms: D000818:Animals; D003470:Culture Media; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D018384:Oxidative Stress; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D003470:Culture Media; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003513:Cycloheximide; D005947:Glucose