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Endoplasmic Reticulum Stress Mediates Palmitic Acid‐induced Insulin Resistance in Skeletal Muscle Cells
Author(s) -
Liu Pingsheng,
Peng Gong,
Li Linhai
Publication year - 2010
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.24.1_supplement.690.4
Subject(s) - insulin resistance , phosphorylation , ampk , medicine , protein kinase b , endoplasmic reticulum , endocrinology , kinase , unfolded protein response , chemistry , protein kinase a , skeletal muscle , insulin , palmitic acid , fatty acid , biology , biochemistry
Pathological elevation of plasma fatty acids reduces insulin sensitivity. We found that insulin‐stimulated phosphorylation of Akt was reduced by palmitic acid (PA). The same treatment also increased phosphorylation of protein kinase R‐like ER kinase (PERK) and XBP‐1 mRNA splicing, which are both up‐regulated in ER stress. 4‐phenyl butyric acid (4‐PBA) blocked PA‐mediated PERK phosphorylation and reversed the inhibitory effect of PA on insulin‐stimulated Akt phosphorylation. Furthermore, oleic acid (OA) could also recover PA‐reduced Akt phosphorylation and abolish both PA‐mediated PERK phosphorylation and XBP‐1 mRNA splicing. The observation was verified in rat skeletal muscle using venous fatty acid infusion. In addition, PA stimulated AMP‐activated protein kinase (AMPK) phosphorylation, and both compound C and OA could inhibit this phosporylation and recover insulin sensitivity. These data suggest that PA induces insulin resistance via AMPK‐mediated ER stress. Our data also demonstrate that OA and PA competitively regulate insulin sensitivity by controlling ER stress.