Structure and physiological role of ATP-sensitive potassium channel

ATP敏感钾通道的结构和生理作用

基本信息

  • 批准号:
    11470009
  • 负责人:
  • 金额:
    $ 9.02万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    1999
  • 资助国家:
    日本
  • 起止时间:
    1999 至 2001
  • 项目状态:
    已结题

项目摘要

ATP-sensitive K^+ (K_<ATP>) channels are key molecules which link the cell's metabolic status to its membrane potential. We have determined that pancreatic β -cell K_<ATP> channel comprises the inward rectifier Kir6.2 and the sulfonylurea receptor SUR1 subunits. Our results are as follows.# We have revealed by immunohistochmical study that SUR1 is expressed not only in pancreatic β -cells but also in glucagon-positive, somatostatin-positive, or pancreatic polypeptide-positive cells. Although the physiological role of the K_<ATP> channels in these cells is unknown, these results suggest that sulfonylureas may exert some effects on these cells through SUR1.# We have developed the method to measure both glucose transport and its effect on the various intracellular functions in single, living pancreatic β -cells, by using a fluorescent derivative of D-glucose, 2-NBDG. By using this novel method, we have revealed that glucose metabolism as well as glucose uptake is critical in glucoseinduced insulin secretion from pancreatic β -cells, verifying the importance of K_<ATP> channels in insulin secretion.# The substantia nigra pars reticulata (SNr), tjae area with the highest expression of K_<ATP> channels in the brain, plays a pivotal role in the control of seizures. We have shown that mutant mice lacking the Kir6.2 subunit of K_<ATP> channels (KO mice) are susceptible to generalized seizures after brief hypoxia. In normal mice, SNr neuron activity was inactivated during hypoxia by the opening of the post-synaptic K_<ATP> channels, while in KO mice the activity of these neurons was enhanced. These results suggest that K_<ATP> channels exert a depressant effect on SNr neuronal activity during hypoxia by an opening of the channels, and is involved in the nigral protection mechanism against generalized seizures.
ATP敏感的K^+通道是连接细胞代谢状态和膜电位的关键分子。我们已确定胰腺β细胞K_1通道由内向整流子Kir6.2和磺脲受体SUR1亚基组成。我们的结果如下:#我们通过免疫组织化学研究发现,SUR1不仅在胰腺β细胞中表达,而且在胰升糖素阳性细胞、生长抑素阳性细胞或胰腺多肽阳性细胞中也有表达。这些结果表明,磺脲类药物可能通过SUR1对这些细胞产生影响。我们已经建立了一种方法,用D-葡萄糖的荧光衍生物2-NBDG来测量单个活的胰腺β细胞中葡萄糖的转运及其对细胞内各种功能的影响。通过这一新的方法,我们揭示了葡萄糖代谢和葡萄糖摄取在糖诱导的胰腺β细胞胰岛素分泌中起关键作用,从而证实了K通道在胰岛素分泌中的重要性。黑质是大脑中K通道表达最高的区域,在控制癫痫发作中起着关键作用。我们已经证明,缺乏K_&lt;ATP&gt;通道Kir6.2亚单位的突变小鼠(KO小鼠)在短暂缺氧后易发生全身性癫痫发作。在正常小鼠中,SNR神经元的活性在低氧时通过开放突触后K_lt;ATP&gt;通道而失活,而在KO小鼠中,这些神经元的活性增强。这些结果表明,K&lt;ATP&gt;通道通过开放通道而抑制低氧时SNR神经元的活动,并参与黑质对全身性惊厥的保护机制。

项目成果

期刊论文数量(68)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yamada, K., et al.: "Measurement of glucose uptake and intracellular calcium concentration in single, living pancreatic β-cells"Journal of Biological Chemistory. 275. 22278-22283 (2000)
Yamada, K. 等人:“单个活胰腺 β 细胞中葡萄糖摄取和细胞内钙浓度的测量”生物化学杂志 275. 22278-22283 (2000)。
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    0
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Sunaga, Y. , et al.: "Troglitazone but not pioglitazone affects ATP-sensitive K^+ channel activity"European Journal of pharmacology. 381. 71-76 (1999)
Sunaga,Y.,等人:“曲格列酮而不是吡格列酮影响 ATP 敏感的 K^ 通道活性”欧洲药理学杂志。
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    0
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Furukawa, T., et al.: "Phosphorylation and functional regulation of CIC-2 chloride channels expressed in Xenopus oocytes by M cyclin-dependent protein kinase"Journal of Physiology. (in press). (2002)
Furukawa, T. 等人:“M 细胞周期蛋白依赖性蛋白激酶对非洲爪蟾卵母细胞中表达的 CIC-2 氯通道的磷酸化和功能调节”生理学杂志。
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    0
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稲垣暢也: "ATP感受性K^+チャネル" 医学のあゆみ. 188. 309-313 (1999)
Nobuya Inagaki:“ATP 敏感 K^+ 通道”医学史 188. 309-313 (1999)。
  • DOI:
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  • 影响因子:
    0
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Sunaga,Y.,Inagaki,N.,Gonoi,T.,Yamada,Y.,Ishida,H.,Seino,Y. et.al.: "Troglitazone but not pioglitazone affects ATP-sensitive K^+ channel activity."Eur.J.Pharmacol.. 381. 71-76 (1999)
须永 Y.、稻垣 N.、五内 T.、山田 Y.、石田 H.、清乃 Y.
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INAGAKI Nobuya其他文献

気道熱傷の病態と治療、そして今後の展望について
呼吸道烧伤的病理学、治疗及未来展望
  • DOI:
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    0
  • 作者:
    MANO Fumika;IKEDA Kaori;SATO Tosiya;NAKAYAMA Takeo;TANAKA Daisuke;JOO Erina;TAKAHASHI Yoshimitsu;KOSUGI Shinji;SEKINE Akihiro;TABARA Yasuharu;MATSUDA Fumihiko;INAGAKI Nobuya;Nagahama Study Group;田崎修
  • 通讯作者:
    田崎修

INAGAKI Nobuya的其他文献

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{{ truncateString('INAGAKI Nobuya', 18)}}的其他基金

Development of a noninvasive method for beta cell mass measurement using a nuclear magnetic resonance
开发使用核磁共振测量 β 细胞质量的无创方法
  • 批准号:
    25670258
  • 财政年份:
    2013
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Development of the novel diagnostic method for quantification ofpancreatic beta-cell mass by magnetic resonance imaging
开发通过磁共振成像定量胰腺β细胞质量的新诊断方法
  • 批准号:
    22390185
  • 财政年份:
    2010
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular Basis of Novel Membrane Transport Mechanism
新型膜传输机制的分子基础
  • 批准号:
    15GS0301
  • 财政年份:
    2003
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Creative Scientific Research
Development of drugs which open or close ATP-sensitive KィイD1+ィエD1channels
开发打开或关闭 ATP 敏感 KiiD1+iED1 通道的药物
  • 批准号:
    10557002
  • 财政年份:
    1998
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Elucidation of the mechanisms underlying the regulation of ATP-sensitive K^+ channels by sulfonylureas
阐明磺酰脲类药物调节 ATP 敏感 K^ 通道的机制
  • 批准号:
    09671025
  • 财政年份:
    1997
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Cloning and functional characterization of inwardly rectifying K^+ channels expressed in pancreatic beta-cells
胰腺β细胞中表达的内向整流K^通道的克隆和功能表征
  • 批准号:
    07671107
  • 财政年份:
    1995
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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血小板对维持胰腺β细胞质量和糖尿病发展的影响(B10)
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开发快速且廉价的基于荧光素酶的高通量筛选测定法,以识别改变胰腺β细胞功能的化合物
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IL-22 作为胰腺β细胞应激的抑制剂和糖尿病的治疗
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宫内营养不良影响出生后胰岛β细胞形成和功能的因素分析
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研究 GSK-3β 在调节胰腺 β 细胞质量中的作用及其在 2 型糖尿病治疗中的应用。
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Pancreatic β cell imaging using 64Cu- or 68Ga-labeled Exendin-4
使用 64Cu 或 68Ga 标记的 Exendin-4 进行胰腺 β 细胞成像
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    21791228
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The roles of transcription factor FoxO1 in pancreatic β cell proliferation and neogenesis
转录因子FoxO1在胰腺β细胞增殖和新生中的作用
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