Liu Feng, Yang Tao, Wang Bin, Zhang Min, Gu Nan, Qiu Jie, Fan Hong-qi, Zhang Chun-mei, Fei Li, Pan Xiao-qing, Guo Mei, Chen Rong-hua, Guo Xi-rong
Department of Pediatrics, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing, China.
Acta Pharmacol Sin. 2008 Jan;29(1):98-104. doi: 10.1111/j.1745-7254.2008.00709.x.
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-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.
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.
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.
本研究旨在观察抵抗素对大鼠原代肝细胞胰岛素敏感性和葡萄糖输出的影响。
培养大鼠肝癌细胞系H4IIE并用抵抗素刺激；检测上清液中的葡萄糖和糖原含量。通过蛋白质印迹法评估胰岛素受体底物（IRS）-1和IRS-2、蛋白激酶B/Akt、糖原合酶激酶-3β（GSK-3β）、细胞因子信号转导抑制因子3（SOCS-3）的蛋白含量以及磷酸化状态。使用针对SOCS-3的特异性反义寡脱氧核苷酸来敲低SOCS-3。
抵抗素诱导大鼠肝癌细胞系H4IIE产生胰岛素抵抗，但不影响其葡萄糖输出。抵抗素减弱了胰岛素的多种作用，包括胰岛素刺激的糖原合成以及IRS、蛋白激酶B/Akt和GSK-3β的磷酸化。抵抗素处理显著诱导了SOCS-3的基因和蛋白表达，SOCS-3是一种已知的胰岛素信号抑制剂。此外，针对SOCS-3的特异性反义寡脱氧核苷酸处理可防止抵抗素拮抗胰岛素作用。
抵抗素在肝脏中的主要功能是诱导胰岛素抵抗。SOCS-3的诱导可能有助于抵抗素介导的对H4IIE肝细胞中胰岛素信号的抑制。
