Differential effects of glucose on dehydroascorbic acid transport and intracellular ascorbate accumulation in astrocytes and skeletal myocytes.
Skeletal muscle and brain are major sites of glucose transport and ascorbate (vitamin C) storage. Ascorbate is oxidized to dehydroascorbic acid (DHAA) when used as an enzyme cofactor or free radical scavenger. We evaluated the hypothesis that glucose regulates DHAA uptake and reduction to ascorbate (i.e., recycling) by skeletal muscle cells and cerebral astrocytes. DHAA uptake was inhibited partially by glucose added simultaneously with DHAA. Comparison of wild type L6 skeletal muscle cells with an L6-derived cell line (D23) deficient in facilitative hexose transporter isoform 3 (GLUT3), indicated that both GLUT3 and facilitative hexose transporter isoform 1 (GLUT1) mediate DHAA uptake. Preincubation of muscle cells with glucose inhibited the rates of glucose and DHAA uptake, and decreased the intracellular concentration of ascorbate derived from recycling of DHAA. In contrast, glucose preincubation did not depress GLUT1 protein and activity levels or DHAA recycling in astrocytes. These results establish that glucose downregulates subsequent recycling of DHAA by skeletal muscle cells but not astrocytes.
Korcok
Jasminka
J
Department of Physiology and Pharmacology, Faculty of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada N6A 5C1.
Dixon
S Jeffrey
SJ
Lo
Theodore C Y
TC
Wilson
John X
JX
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001692:Biological Transport; D015153:Blotting, Western; D002247:Carbon Isotopes / Q000378:metabolism; D002460:Cell Line; D003572:Cytochalasins / Q000494:pharmacology; D003683:Dehydroascorbic Acid / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects*; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology; D051381:Rats; D012964:Sodium / Q000172:deficiency / Q000494:pharmacology; D013442:Sulfinpyrazone / Q000494:pharmacology; D013997:Time Factors; D014528:Uricosuric Agents / Q000494:pharmacology
D002247:Carbon Isotopes; D003572:Cytochalasins; D014528:Uricosuric Agents; D012964:Sodium; D005947:Glucose; D001205:Ascorbic Acid; D013442:Sulfinpyrazone; D003683:Dehydroascorbic Acid