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 journalArticlepeer-review

28 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

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012006363) (K.M.C.) and by the Brain Korea 21 Project of the Ministry of Education and Human Resources Development, Republic of Korea (K.M.C. and S.H.B.).

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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