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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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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