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. © 1990.