AMPK activator-mediated inhibition of endoplasmic reticulum stress ameliorates carrageenan-induced insulin resistance through the suppression of selenoprotein P in HepG2 hepatocytes

Tae Woo Jung, So Young Lee, Ho Cheol Hong, Hae Yoon Choi, Hye Jin Yoo, Sei Hyun Baik, Kyung Mook Choi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)66-73
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume382
Issue number1
DOIs
Publication statusPublished - 2014 Jan 25

Keywords

  • AMPK
  • ER stress
  • Hepatokine
  • Insulin resistance
  • Salsalate
  • Selenoprotein P

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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