Subcellular localization of glucose transporter 4 in the hypothalamic arcuate nucleus of ob/ob mice under basal conditions
Subcellular localization of glucose transporter 4 in the hypothalamic arcuate nucleus of ob/ob mice under basal conditions
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DOI：
10.1016/j.brainres.2005.04.079
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发表时间：
2005-07-05
期刊：
影响因子：
2.9
通讯作者：
Senba, E
中科院分区：
文献类型：
--
作者：
Komori, T;Morikawa, Y;Senba, E
葡萄糖转运蛋白（GLUT） 4在胰岛素诱导的骨骼肌和白色脂肪组织的葡萄糖摄取中起重要作用。虽然GLUT4在下丘脑和这些外周组织中含量丰富，但对GLUT4在下丘脑中的作用知之甚少。在本研究中，我们研究了在基础条件下ob/ob小鼠下丘脑弓状核中GLUT4的亚细胞定位和胰岛素信号通路的激活。GLUT4在ob/ob小鼠弓形核中的表达高于瘦小鼠。有趣的是，与瘦小鼠相比，ob/ob小鼠弓形核神经元质膜上的GLUT4显著增加。由于ob/ob小鼠的血清胰岛素水平非常高，我们假设胰岛素强烈刺激ob/ob小鼠弓形核中的GLUT4易位。出乎意料的是，在瘦小鼠和ob/ob小鼠的下丘脑中，IR和胰岛素受体底物-1 （IRS-1）的酪氨酸磷酸化很微弱。此外，与瘦小鼠相比，ob/ob小鼠下丘脑中IRS-1 Ser（307）位点的磷酸化水平更高，这表明ob/ob小鼠下丘脑中IRS-1 Ser（307）位点的磷酸化会损害胰岛素信号。然而，与瘦小鼠相比，ob/ob小鼠弓形核中Akt的丝氨酸磷酸化显著增加。此外，脑源性神经营养因子（神经元中PI3K-Akt通路的激活剂）在ob/ob小鼠下丘脑腹内侧的表达显著增加。我们讨论了在ob/ob小鼠弓形核中诱导GLUT4易位的新途径的可能性。(c) 2005 Elsevier B.V.版权所有
Glucose transporter (GLUT) 4 plays an important role in insulin-induced glucose uptake in skeletal muscle and white adipose tissue. Although GLUT4 is abundant in the hypothalamus as well as in these peripheral tissues, little is known about the role of GLUT4 in the hypothalamus. In this study, we examined the subcellular localization of GLUT4 and the activation of insulin signaling pathways in the hypothalamic arcuate nucleus of ob/ob mice under basal conditions. The expression of GLUT4 in the arcuate nucleus of ob/ob mice was higher than that in lean mice. Interestingly, GLUT4 on the plasma membrane increased significantly in neurons of the arcuate nucleus of ob/ob mice when compared to that in lean mice. Because serum insulin levels of ob/ob mice were very high, we hypothesized that insulin strongly stimulates GLUT4 translocation in the arcuate nucleus of ob/ob mice. Unexpectedly, tyrosine phosphorylation of IR and insulin receptor substrate-1 (IRS-1) was faint in the hypothalamus of lean and ob/ob mice. In addition, phosphorylation of IRS-1 at Ser(307) in the hypothalamus of ob/ob mice was higher when compared to that in lean mice, suggesting that insulin signaling is impaired by phosphorylation of IRS-1 at Ser(307) in the hypothalamus of ob/ob mice. However, serine phosphorylation of Akt in the arcuate nucleus of ob/ob mice increased significantly when compared to that in lean mice. Furthermore, the expression of brain-derived neurotrophic factor, an activator of PI3K-Akt pathway in neurons, increased significantly in the ventromedial hypothalamus of ob/ob mice. We discuss the possibility of novel pathways which induce the translocation of GLUT4 in the arcuate nucleus of ob/ob mice. (c) 2005 Elsevier B.V. All rights reserved.