Endocrine Pharmacology

Resistin induces insulin resistance, but does not affect glucose output in rat-derived hepatocytes

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The aim of the present study was to observe the effects of resistin on insulin sensitivity and glucose output in rat-derived hepatocytes.


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.


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.


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.


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Author information

Correspondence to Rong-hua Chen or Xi-rong Guo.

Additional information

This study was supported by grants from the National Natural Science Foundation of China (No 30371502 and 30571978), the Natural Science Foundation of Jiangsu Province (No BK2001120), and a grant from Jiangsu Province Health Department (No RC2002061).

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  • resistin
  • hepatocytes
  • insulin resistance
  • suppressor of cytokine signaling 3

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