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Mechanism of neural stimulation of glucose transport in certain tissues

某些组织中葡萄糖转运的神经刺激机制

基本信息

批准号：
04454172
负责人：
SHIMAZU Takashi
金额：
$ 4.29万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

Our recent studies have demonstrated that electrical and chemical stimulation of the ventromedial hypothalamus (VMH) enhances glucose uptake in brown adipose tissue, heart and skeletal muscles preferentially. We now show that the effect of VMH stimulation in enhancing glucose uptake in skeletal muscle was effectively suppressed by the sympathetic neuron blocking agent, guanethidine. In addition, the beta_3-adrenergic agonist, BRL35135A,was shown to mimic the effects of VMH stimulation, suggesting that the sympathetic-nerve action on glucose uptake was mediated by beta_3-adrenoceptors.We have established culture conditions for brown adipocytes which are favorable for analyzing mechanism of enhancement of glucose transport by norepinephrine (NE). Both NE and insulin increased dose-dependently glucose transport into cultured brown adipocytes, and both effects were additive. The effect of insulin was dependent upon translocation of the GLUT4 glucose transporter from microsome to plasma membranes, whereas NE did not affect the subcellular distribution of GLUT4.Moreover, when Wortmannin, a selective inhibitor of phosphatidylinositol (PI) 3-kinase, was added to the medium before stimulation with insulin, the increase in glucose transport and translocation of GLUT4 were completely suppressed. In contrast, NE-induced increase in glucose transport was resistant to Wortmannin. The results indicate that PI 3-kinase plays a critical role on insulin-induced translocation of GLUT4, but that this pathway is not involved in the increased activity of glucose transport induced by NE.

我们最近的研究表明，电和化学刺激下丘脑腹内侧核(VMH)优先增加棕色脂肪组织、心脏和骨骼肌对葡萄糖的摄取。我们现在发现，刺激VMH促进骨骼肌摄取葡萄糖的作用可被交感神经元阻滞剂金刚乙胺有效地抑制。此外，β_3-肾上腺素能激动剂BRL35135A可模拟VMH刺激的作用，提示交感神经对葡萄糖摄取的作用是通过β_3-肾上腺素能受体介导的。去甲肾上腺素和胰岛素均可剂量依赖性地增加葡萄糖在培养的棕色脂肪细胞中的转运，且这两种作用是相加的。胰岛素的作用依赖于GLUT4葡萄糖转运体从微粒体到质膜的移位，而NE不影响GLUT4的亚细胞分布。此外，在胰岛素刺激前加入磷脂酰肌醇(PI)3-激酶的选择性抑制剂Wortmannin，可完全抑制葡萄糖转运和GLUT4移位的增加。相反，去甲肾上腺素诱导的葡萄糖转运增加对Wortmannin具有抵抗力。结果表明，PI-3-K在胰岛素诱导的GLUT4转位中起关键作用，但该途径不参与NE诱导的葡萄糖转运活性的增加。