Resistin induces insulin resistance, but does not affect glucose output in rat-derived hepatocytes.
OBJECTIVE
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-3beta(GSK-3 beta), 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-3beta. 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.


CONCLUSIONS
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.
Liu
Feng
F
Department of Pediatrics, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing, China.
Yang
Tao
T
Wang
Bin
B
Zhang
Min
M
Gu
Nan
N
Qiu
Jie
J
Fan
Hong-qi
HQ
Zhang
Chun-mei
CM
Fei
Li
L
Pan
Xiao-qing
XQ
Guo
Mei
M
Chen
Rong-hua
RH
Guo
Xi-rong
XR
D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D052243:Resistin / Q000494:pharmacology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
D007329:Insulin Antagonists; D055504:Insulin Receptor Substrate Proteins; C526299:Irs2 protein, rat; D020320:Oligoribonucleotides, Antisense; D052243:Resistin; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D012313:RNA; D006003:Glycogen; D005947:Glucose