Acta Pharmacologica Sinica 2008 January; 29 (1): 98-104; doi: 10.1111/j.1745-7254.2008.00709.x

Acta Pharmacologica Sinica 2008 January; 29 (1): 98-104; doi: 10.1111/j.1745-7254.2008.00709.x

Original Article

Resistin induces insulin resistance, but does not affect glucose output in rat-derived hepatocytes¹

Feng LIU^2,3,5, Tao YANG^4,5, Bin WANG³, Min ZHANG³, Nan GU³,Jie QIU³, Hong-qi FAN³,Chun-mei ZHANG³, Li FEI³,Xiao-qing PAN³,Mei GUO³,Rong-hua CHEN^2,3,6, Xi-rong GUO^2,3,6

²Department of Pediatrics, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China; ³Institute of Pediatrics of Nanjing Medical University, Nanjing 210029, China; ⁴Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

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

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.

Keywords: resistin; hepatocytes; insulin resistance; suppressor of cytokine signaling 3

¹This 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).

⁵These authors contributed equally to this work.
⁶Correspondence to Prof Xi-rong GUO and Dr Rong-hua CHEN.
Phn 86-25-8686-2996.
E-mail xrguo@njmu.edu.cn (Xi-rong GUO)
Phn 86-25-8686-2997.
E-mail rhchen@njmu.edu.cn (Rong-hua CHEN)
Received 2007-03-16 Accepted 2007-07-16

[ Full text]