# name
Neuregulin signaling on glucose transport in muscle cells

# metadata.dc.description.abstract[].value
Neuregulin-1, a growth factor that potentiates myogenesis induces glucose transport through translocation of glucose transporters, in an additive manner to insulin, in muscle cells. In this study, we examined the signaling pathway required for a recombinant active neuregulin-1 isoform (rhHeregulin-β1, 177-244, HRG) to stimulate glucose uptake in L6E9 myotubes. The stimulatory effect of HRG required binding to ErbB3 in L6E9 myotubes. PI3K activity is required for HRG action in both muscle cells and tissue. In L6E9 myotubes, HRG stimulated PKBα, PKBγ, and PKCζ activities. TPCK, an inhibitor of PDK1, abolished both HRG- and insulin-induced glucose transport. To assess whether PKB was necessary for the effects of HRG on glucose uptake, cells were infected with adenoviruses encoding dominant negative mutants of PKBα. Dominant negative PKB reduced PKB activity and insulin-stimulated glucose transport but not HRG-induced glucose transport. In contrast, transduction of L6E9 myotubes with adenoviruses encoding a dominant negative kinase-inactive PKCζ abolished both HRG- and insulin-stimulated glucose uptake. In soleus muscle, HRG induced PKCζ, but not PKB phosphorylation. HRG also stimulated the activity of p70S6K, p38MAPK, and p42/p44MAPK and inhibition of p42/p44MAPK partially repressed HRG action on glucose uptake. HRG did not affect AMPKα1 or AMPKα2 activities. In all, HRG stimulated glucose transport in muscle cells by activation of a pathway that requires PI3K, PDK1, and PKCζ, but not PKB, and that shows cross-talk with the MAPK pathway. The PI3K, PDK1, and PKCζ pathway can be considered as an alternative mechanism, independent of insulin, to induce glucose uptake.

# metadata.dc.publisher[].value
American Society for Biochemistry and Molecular Biology

# metadata.dc.rights[].value
(c) American Society for Biochemistry and Molecular Biology, 2004

# metadata.dc.source[].value
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

# metadata.dc.title[].value
Neuregulin signaling on glucose transport in muscle cells