Regulation of hexose transport in L8 myocytes by glucose: possible sites of interaction.
Previous work demonstrated that glucose controls its own transport rate in rat skeletal muscle: exposure to high glucose levels down-regulates muscle hexose transport, while glucose withdrawal results in elevated transport rates (J. Biol. Chem. 261:16827-16833, 1986). The present study investigates the mechanism of this autoregulatory system. Preincubation of L8 myocytes at 16 mM glucose reduced subsequent 2-deoxy-D-glucose (dGlc) uptake by 40% within 3 h. Cycloheximide (1 microM) mimicked the action of glucose; the effects of glucose and cycloheximide were not additive. At 50 microM, cycloheximide prevented the modulations of glucose transport induced by exposure of muscle cells to high or low glucose concentrations. Inhibition of glycosylation with tunicamycin A1 reduced the basal dGlc uptake, but did not prevent its up-regulation following glucose withdrawal. Inhibition of RNA synthesis by actinomycin D prevented the down-regulatory effect of glucose. These results indicate that continuous protein synthesis and protein glycosylation are required for the maintenance of the steady-state dGlc uptake. We suggest that glucose exerts its autoregulatory effect on hexose transport by modifying the incorporation of active glucose transporters into the plasma membrane rather than changing their rate of degradation. It is hypothesized that this effect is mediated by a non-glycosylated protein involved in the translocation or activation of glucose transporters.
Wertheimer
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Department of Endocrinology and Metabolism, Hebrew University Hadassah Medical Center, Jerusalem, Israel.
Sasson
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S
Cerasi
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D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005246:Feedback; D005947:Glucose / Q000502:physiology*; D006031:Glycosylation; D066298:In Vitro Techniques; D007700:Kinetics; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D051381:Rats; D014415:Tunicamycin / Q000494:pharmacology
D009004:Monosaccharide Transport Proteins; D014415:Tunicamycin; D003609:Dactinomycin; D003513:Cycloheximide; D005947:Glucose