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AMPK activator-mediated inhibition of endoplasmic reticulum stress ameliorates carrageenan-induced insulin resistance through the suppression of selenoprotein P in HepG2 hepatocytes
- Jung, Tae Woo, Lee, So Young, Hong, Ho Cheol, Choi, Hae Yoon, Yoo, Hye Jin, Baik, Sei Hyun, Choi, Kyung Mook
- Molecular and Cellular Endocrinology 2014 v.382 pp. 66-73
- AMP-activated protein kinase, Toll-like receptor 4, binding proteins, carrageenan, endoplasmic reticulum, hepatocytes, human cell lines, inflammation, insulin resistance, mitogen-activated protein kinase, noninsulin-dependent diabetes mellitus, selenoproteins
- Carrageenan (CGN) has been shown to cause inflammation through toll-like receptor 4, which may play an important role in insulin resistance and type 2 diabetes mellitus. Selenoprotein P (SeP) has recently been identified as a novel hepatokine that causes insulin resistance. Here, we report that treatment of HepG2 cells with CGN increased both CCAAT enhancer binding protein homologous protein (CHOP) and SeP expression. Pretreatment with 4-phenylbutyrate (4-PBA), an endoplasmic reticulum stress inhibitor, and PD98059, a c-Jun N-terminal kinase (JNK) inhibitor, reversed CGN-induced SeP expression. Moreover, both 4-PBA and knock-down of SeP improved CGN-induced insulin resistance. In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activators ameliorated CGN-induced insulin resistance in addition to suppressing CHOP and SeP expression. In conclusion, CGN-induced ER stress increased the expression of SeP through the JNK pathway, while AMPK activators ameliorated CGN-induced insulin resistance via SeP inhibition through the AMPK-mediated alleviation of ER stress in hepatocytes.