Kralisch Susan, Klein Johannes, Lossner Ulrike, Bluher Matthias, Paschke Ralf, Stumvoll Michael, Fasshauer Mathias
University of Leipzig, Department of Internal Medicine III, 04103 Leipzig, Germany.
Regul Pept. 2006 Jul 15;135(1-2):12-6. doi: 10.1016/j.regpep.2006.03.002. Epub 2006 Apr 27.
Recently, monocyte chemoattractant protein (MCP)-1 has been characterized as a novel adipocytokine upregulated in obesity and insulin resistance which impairs insulin signaling in muscle and fat in vitro. Growing evidence, on the other hand, suggests that increased activity of the sympathetic nervous system is an integral part in the development of insulin resistance. In the current study, the impact of the beta-adrenergic agonist isoproterenol on MCP-1 mRNA synthesis and secretion was determined in 3T3-L1 adipocytes. Interestingly, isoproterenol increased MCP-1 secretion 3-fold. Furthermore, 10 microM isoproterenol acutely induced MCP-1 mRNA by up to 5.3-fold in a time-dependent fashion with significant stimulation seen at concentrations as low as 0.3 microM effector. Studies using pharmacological inhibitors suggested that basal and isoproterenol-induced MCP-1 expressions are mediated via beta-adrenergic receptors and protein kinase A. Moreover, acute activation of adenylyl cyclase by forskolin was sufficient to mimic the effects of isoproterenol. Taken together, our results demonstrate that isoproterenol induces MCP-1 expression and secretion via a classical GS-protein-coupled pathway and support the notion that MCP-1 might be an interesting novel candidate linking obesity and insulin resistance.
最近，单核细胞趋化蛋白（MCP）-1已被鉴定为一种新型脂肪细胞因子，在肥胖和胰岛素抵抗中上调，在体外会损害肌肉和脂肪中的胰岛素信号传导。另一方面，越来越多的证据表明，交感神经系统活动增加是胰岛素抵抗发展的一个组成部分。在本研究中，测定了β-肾上腺素能激动剂异丙肾上腺素对3T3-L1脂肪细胞中MCP-1 mRNA合成和分泌的影响。有趣的是，异丙肾上腺素使MCP-1分泌增加了3倍。此外，10μM异丙肾上腺素以时间依赖性方式急性诱导MCP-1 mRNA增加高达5.3倍，在低至0.3μM效应物浓度时即可观察到显著刺激。使用药理学抑制剂的研究表明，基础和异丙肾上腺素诱导的MCP-1表达是通过β-肾上腺素能受体和蛋白激酶A介导的。此外，福斯可林对腺苷酸环化酶的急性激活足以模拟异丙肾上腺素的作用。综上所述，我们的结果表明，异丙肾上腺素通过经典的GS蛋白偶联途径诱导MCP-1表达和分泌，并支持MCP-1可能是连接肥胖和胰岛素抵抗的一个有趣的新候选者这一观点。
