GLUCOSE-TRANSPORTER EXPRESSION IN L6 MUSCLE-CELLS - REGULATION THROUGH INSULIN-ACTIVATED AND STRESS-ACTIVATED PATHWAYS

We addressed the effect of long-term treatment with insulin, 2,4-dinit rophenol (DNP; an uncoupler of oxidative phosphorylation that increase s energy demand) and 300 mM mannitol (hyperosmolarity) on glucose tran sporter (GLUT) expression in L6 muscle cells and the signaling pathway s involved. We found the following. 1) The insulin-mediated increase i n GLUT-1 is 70-kDa ribosomal protein S6 kinase (p70 S6 kinase) and p38 mitogen-activated protein kinase (MAPK) dependent but extracellular s ignal-regulated protein kinase (ERK) and MAPK/ERK kinase (MEK) indepen dent. The hypertonicity-stimulated elevation in GLUT-1 is p70 S6 kinas e, p38 MAPK, and MEK dependent vet ERK independent. DNP also increased GLUT-1 protein but did not depend on any of the above pathways. 2) In sulin increased GLUT-3 protein in a p70 S6 kinase-independent but MEK/ ERK-dependent fashion. Inhibition of p38 MAPK potentiated the effect o f insulin on GLUT-3. Hypertonicity increased GLUT-3 via p70 S6 kinase- and p38 MAPK-dependent pathways. In conclusion, we have dissected the molecular mechanisms used by insulin and hypertonicity that culminate in the induction of GLUT-1 and GLUT-3. The mechanism(s) used by DNP r emains unknown.