Open AccessResistin induces insulin resistance, but does not affect glucose output in rat‐derived hepatocytes 1
Author(s) -
LIU Feng,
YANG Tao,
WANG Bin,
ZHANG Min,
GU Nan,
QIU Jie,
FAN Hongqi,
ZHANG Chunmei,
FEI Li,
PAN Xiaoqing,
GUO Mei,
CHEN Ronghua,
GUO Xirong
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00709.x
Subject(s) - resistin , insulin resistance , medicine , endocrinology , glycogen synthase , protein kinase b , insulin receptor , insulin , insulin receptor substrate , irs2 , biology , gsk 3 , phosphorylation , microbiology and biotechnology , adipokine
Aim : The aim of the present study was to observe the effects of resistin on insulin sensitivity and glucose output in rat‐derived hepatocytes. Methods : The rat hepatoma cell line H4IIE was cultured and stimulated with resistin; supernant glucose and glycogen content were detected. The insulin receptor substrate (IRS)‐1 and IRS‐2, protein kinase B/Akt, glycogen synthase kinase‐3β (GSK‐3β), the suppressor of cytokine signaling 3 (SOCS‐3) protein content, as well as the phosphorylation status were assessed by Western blotting. Specific antisense oligodeoxynucleotides directed against SOCS‐3 were used to knockdown SOCS‐3. Results : Resistin induced insulin resistance, but did not affect glucose output in rat hepatoma cell line H4IIE. Resistin attenuated multiple effects of insulin, including insulin‐stimulated glycogen synthesis and phosphorylation of IRS, protein kinase B/Akt, as well as GSK‐3β. Resistin treatment markedly induced the gene and protein expression of SOCS‐3, a known inhibitor of insulin signaling. Furthermore, a specific antisense oligodeoxynucleotide directed against SOCS‐3 treatment prevented resistin from antagonizing insulin action. Conclusion : The major function of resistin on liver is to induce insulin resistance. SOCS‐3 induction may contribute to the resistin‐mediated inhibition of insulin signaling in H4IIE hepatocytes.