| Project/Area Number |
04454172
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Ehime University |
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Principal Investigator |
SHIMAZU Takashi Ehime University, School of Medicine, Professor, 医学部, 教授 (30090400)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Yasutake Ehime University, School of Medicine, Assistant Professor, 医学部, 助手 (40243802)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1992: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | glucose transport / glucose transporter (GLUT4) / sympathetic nervous system / norepinephrine / beta_3-adrenergic agonist / insulin / brown adipocytes / skeletal muscle / GLUT4 / ワ-トマニン / GLUT1 / グルコース輸送活性 / β_3-アゴニスト / 2-デオキシグルコース法 / 骨格筋 / 褐色脂肪組織 |
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| Research Abstract |
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.
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