The role of the GLUT 4 transporter in regulating rat myoblast glucose transport processes

Abstract

Previous studies revealed an inverse relationship between GLUT 1 and GLUT 4 expression in rat myoblasts [L. Xia, Z. Lu, T.C.Y. Lo, J. Biol. Chem., 268 (1993) 23258-23266]. It was not clear whether these were coincidental or causal occurrences. To examine the regulatory roles of the GLUT 4 isoform, rat L6 myoblasts were transfected with full length GLUT 4 cDNAs (2.5 kb) in the sense or antisense orientation. L6 myoblasts transfected with the GLUT 4 sense cDNA (L6/G4S transfectants) possessed much elevated levels of both endogenous GLUT 4 transcripts (1.4 kb and 2.8 kb). Transport and immunofluorescence studies showed that this GLUT 4 sense cDNA was responsible for a functional GLUT 4 transporter. L6 cells transfected with the GLUT 4 antisense cDNA (L6/G4A transfectants) possessed only 6% of the L6 level in day 6 cultures. These antisense transfectants were essentially devoid of any functional GLUT 4 transporter. The activation of transcription of the endogenous GLUT 4 gene in L6/G4S myoblasts suggested auto-regulation of GLUT 4 expression. GLUT 3 expression and activity were not altered in both sense and antisense GLUT 4 transfectants. More interestingly, GLUT 1 expression was reduced in L6/G4S myoblasts, whereas it was elevated in L6/G4A myoblasts. This was the first direct evidence indicating GLUT 4 might play an important role in suppressing GLUT 1 expression.

25-hydroxyvitamin D upregulates L6 muscle cell differentiation induced by mononuclear cells via the Notch signaling pathway

“…Finally, an overexpression of genes implicated in some energetic metabolism pathways was observed. This included proteolysis (Fbxo32) as described before (41), glucose transport (Slc2a4) as shown in Broydell's study (42) and calcium in ux (Atp2a1) which plays an essential role in the regulation of intracellular Ca 2+ level and in the skeletal muscle differentiation (43). Taken together, these observations con rm the hypothesis of the crosstalk between immune and muscle cells to promote metabolic changes and muscle differentiation.…”