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Low Receptor Interacting Protein 140 (RIP140) Expression Adversely Impacts Proximal Insulin Signaling in L6 Skeletal Muscle Cells
Author(s) -
Constantinescu Silvana,
Turcotte Lorraine P
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb584
Subject(s) - protein kinase b , insulin , insulin receptor , medicine , myogenesis , phosphorylation , chemistry , microbiology and biotechnology , endocrinology , glucose uptake , skeletal muscle , biology , insulin resistance
We have shown that reduced expression of receptor interacting protein 140 (RIP140) alters the regulation of muscle fatty acid (FA) uptake and FA oxidation under basal and insulin‐stimulated conditions. To provide mechanistic insights for these changes, we measured the gene expression and protein content of proteins known to be involved in metabolic regulation. L6 myotubes were silenced using RNAi sequences for either RIP140 (RIP) or a negative control (NC) and incubated ± insulin (I: 1000 nM). As expected, RIP140 protein content (53%) and gene expression (37%) were decreased ( P <0.05) in RIP cells. Low RIP140 expression increased ( P <0.05) nerve growth factor IB (Nur77) gene expression (92%) but did not affect medium chain acyl‐CoA dehydrogenase (MCAD) expression. In NC cells, insulin did not affect MCAD or Nur77 expression while it decreased ( P <0.05) Nur77 expression in RIP cells. Insulin increased fibroblast growth factor 21(FGF21) protein content in NC cells, but it had no effect in RIP cells. Low RIP140 expression increased basal AKT Ser473 phosphorylation and prevented the insulin‐induced increase in AKT Ser473 , AKT Thr308 or PKC‐ξ Thr408/410 phosphorylation. We conclude that low RIP140 expression directly affects the expression of several proteins associated with metabolic regulation and adversely impacts the induction of proximal insulin signaling. USC Women in Science and Engineering, USC Integrative and Evolutionary Biology and USC Zumberge Research Innovation Fund