Glucose starvation and glycosylation inhibitors reduce insulin receptor gene expression: characterization and potential mechanism in human cells.
Glucose affects the expression of several genes in many cell types. In this work (i) we stably cultured three human cell lines in media containing different glucose concentrations (from 0 to 25 mM), (ii) we characterized glucose effects on insulin receptor gene expression, (iii) we investigated the mechanism by which glucose produces these effects. We found that: (i) glucose starvation reduces insulin receptor gene expression likely affecting insulin receptor gene transcription rates; (ii) a hexose that undergoes to interconversion with glucose metabolites (D-fructose), added to low-glucose media, increases either insulin receptor mRNA levels or insulin binding activity, while hexoses unable to enter the cell (L-glucose) or not metabolizable (3-O-methylglucose), do not produce any effect; (iii) glycosylation inhibitors (2-deoxyglucose and tunicamycin) reduce, in a time-dependent manner, insulin receptor mRNA levels. Our data indicate that glucose affects insulin receptor gene expression in human cells and that protein glycosylation plays a role in this regulatory mechanism.
Immunobiology Laboratory, National Cancer Institute (I.S.T.), Genova, Italy.
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D015152:Blotting, Northern; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006601:Hexoses / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007700:Kinetics; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D017451:Receptors, Somatomedin; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D006601:Hexoses; D007328:Insulin; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D012313:RNA; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D005947:Glucose