Molecular basis of brain-mediated regulation of hepatic glucose metabolism.
Molecular basis of brain-mediated regulation of hepatic glucose metabolism.
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脑介导的肝葡萄糖代谢调节的分子基础。
DOI：
10.1007/s13340-014-0185-8
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Inoue H.
中科院分区：
文献类型：
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作者：
Okada Y;Oku Y;Yokota S;Oyamada Y;Yasui Y;Koshiya N;安部大地 川中涼子 岡崎純子;Inoue H.
各种体液因子参与调节中枢神经系统和外周组织之间的相互作用介导的能量和葡萄糖代谢。胰岛素严格调节肝脏、骨骼肌和脂肪组织中的葡萄糖代谢，也在脑介导的能量和葡萄糖代谢调节中发挥作用。通过下丘脑，胰岛素不仅调节饮食摄入和餐后产热，还调节肝脏和骨骼肌中的葡萄糖代谢。胰岛素通过迷走神经激活下丘脑神经元中的磷酸肌醇-3-激酶和KATP通道对肝脏发挥作用。中枢胰岛素作用可增强肝枯否细胞分泌白细胞介素-6，并激活转录因子信号转导子和转录激活子3（STAT 3），从而抑制肝细胞中促凋亡酶基因的表达，从而减少肝葡萄糖的产生。脑介导的肝葡萄糖生成抑制也源于血浆组氨酸水平的增加。组氨酸在下丘脑中转化为组胺，其激活肝STAT 3，从而通过下丘脑组胺H1受体抑制致炎酶基因的表达。在肥胖和2型糖尿病中，中枢胰岛素作用对肝脏葡萄糖产生的抑制受损，可能增加肝脏葡萄糖产生。然而，需要进一步的研究来阐明中枢神经系统和外周组织之间相互作用的分子机制。
Various humoral factors are involved in the regulation of energy and glucose metabolism mediated by the interaction between the central nervous system and peripheral tissues. Insulin, which strictly regulates glucose metabolism in the liver, skeletal muscles, and adipose tissue, also plays a role in brain-mediated regulation of energy and glucose metabolism. Through the hypothalamus, insulin regulates not only diet intake and postprandial thermogenesis, but also glucose metabolism in the liver and skeletal muscles. Insulin exerts its action on the liver via the vagus nerve by activating phosphoinositide-3-kinase and KATPchannels in the hypothalamic neurons. Central insulin action enhances the secretion of interleukin-6 from hepatic Kupffer cells and activates the transcription factor signal transducer and activator of transcription 3 (STAT3), which suppresses the expression of gluconeogenic enzyme genes in hepatocytes and thereby reducies hepatic glucose production. Brain-mediated suppression of hepatic glucose production also arises from an increase in the plasma histidine level. Histidine is converted to histamine in the hypothalamus, which activates hepatic STAT3 and thereby suppresses the expression of gluconeogenic enzyme genes via hypothalamic histamine H1 receptors. In obesity and type 2 diabetes, suppression of hepatic glucose production by central insulin action is impaired, potentially increasing hepatic glucose production. However, further studies are needed to elucidate the molecular mechanisms underlying the interaction between the central nervous system and peripheral tissues.