Serotonin modulates hepatic 6-phosphofructo-1-kinase in an insulin synergistic manner
Serotonin modulates hepatic 6-phosphofructo-1-kinase in an insulin synergistic manner
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DOI：
10.1016/j.biocel.2011.10.010
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Sola-Penna, Mauro
中科院分区：
文献类型：
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作者：
Coelho, Wagner Santos;Da Silva, Daniel;Sola-Penna, Mauro
人和大鼠肝组织表达多种5-羟色胺（5-HT）受体亚型，如5-HT1B、5-HT2A、5-HT2B和5-HT7受体，介导多种作用。已知5-HT调节肝脏生物学的几个关键方面，包括肝血流，神经支配和伤口愈合。5-羟色胺也被认为可以提高禁食犬在葡萄糖输注过程中的净葡萄糖摄取，但对5-羟色胺控制肝脏葡萄糖代谢，尤其是糖酵解的能力知之甚少。本研究探讨了5-羟色胺调节PFK活性的潜力及其与酶活性相关的机制。基于我们的研究结果，我们首次提供了5-HT上调小鼠肝组织中PFK的证据。该酶的激活通过5-HT2A受体和磷脂酶C （PLC）发生，导致PFK在细胞内重新分布，并有利于PFK与细胞骨架f-肌动蛋白富集组分的结合。有趣的是，5-HT和胰岛素以协同方式起作用，可能是因为胰岛素增加果糖-2,6-二磷酸的能力，因为这种PFK变构调节剂的存在增强了5-HT对酶活性的影响。总之，这些数据证明了5-HT控制肝糖酵解的能力，并提供了有关这些过程的机制的线索，这可能对理解5-HT在肝伤口愈合过程中的作用很重要。(C) 2011 Elsevier Ltd.版权所有。
Human and rat hepatic tissue express many serotonin (5-HT) receptor subtypes, such as 5-HT1B, 5-HT2A, 5-HT2B and 5-HT7 receptors, which mediate diverse effects. 5-HT is known to regulate several key aspects of liver biology including hepatic blood flow, innervations and wound healing. 5-HT is also known to enhance net glucose uptake during glucose infusion in fasted dogs, but little is known about the ability of 5-HT to control hepatic glucose metabolism, especially glycolysis. This study addresses the potential of 5-HT to regulate PFK activity and the mechanisms related to the enzyme activity. Based on our results, we are the first to provide evidence that 5-HT up-regulates PFK in mouse hepatic tissue. Activation of the enzyme occurs through the 5-HT2A receptor and phospholipase C (PLC), resulting in PFK intracellular redistribution and favoring PFK association to the cytoskeletal f-actin-enriched fractions. Interestingly, 5-HT and insulin act in a synergistic manner, likely because of the ability of insulin to increase fructose-2,6-bisphosphate because the presence of this PFK allosteric regulator enhances the 5-HT effect on the enzyme activity. Together, these data demonstrate the ability of 5-HT to control hepatic glycolysis and present clues about the mechanisms involved in these processes, which may be important in understanding the action of 5-HT during the hepatic wound healing process. (C) 2011 Elsevier Ltd. All rights reserved.