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

作　　者：Feng LIU Tao YANG Bin WANG Min ZHANG Nan GU Jie QIU Hong-qi FAN Chun-mei ZHANG Li FEI Xiao- qing PAN Mei GUO Rong-hua CHEN Xi-rong GUO 

机构地区：[1]Department of Pediatrics, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China [2]Institute of Pediatrics of Nanjing Medical University, Nanjing 210029, China [3]Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

出　　处：《Acta Pharmacologica Sinica》2008年第1期98-104,共7页中国药理学报（英文版）

基　　金：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）.

摘　　要：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.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.

关 键 词：RESISTIN HEPATOCYTES insulin resistance suppressor of cytokine signaling 3 

分 类 号：R587.1[医药卫生—内分泌]