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Closure by iptakalim, a cardiovascular KATP channel opener, of rat pancreatic β-cell KATP channels and its molecular basis
http://hdl.handle.net/10129/2222
http://hdl.handle.net/10129/22222ec31de6-a469-4b2c-902b-bccd3830169c
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
HirosakiMedJ_59_S89.pdf (220.9 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2009-09-18 | |||||
| タイトル | ||||||
| タイトル | Closure by iptakalim, a cardiovascular KATP channel opener, of rat pancreatic β-cell KATP channels and its molecular basis | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | iptakalim | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | K_ATP channel | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Kir6.2 | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | β-cell | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | insulin secretion | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
Wakui, Makoto
× Wakui, Makoto× Misaki, Naoko× Suga, Sechiko× Mao, Xia× Lin, Yu-Fung× Wu, Jie |
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| 著者所属 | ||||||
| 値 | Division of Clinical Research, Hirosaki National Hospital | |||||
| 著者所属 | ||||||
| 値 | Department of Physiology, Hirosaki University, Graduate School of Medicine | |||||
| 著者所属 | ||||||
| 値 | Department of Physiology and Membrane Biology, University of California, Davis, School of Medicine | |||||
| 著者所属 | ||||||
| 値 | Division of Neurology, Barrow Neurological Institute | |||||
| 著者所属 | ||||||
| 値 | Division of Neurology, Barrow Neurological Institute | |||||
| 著者所属 | ||||||
| 値 | Division of Neurology, Barrow Neurological Institute | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Diabetes mellitus is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. Diabetes patients usually have accompanying cardiovascular disorders. Sulfonylureas have been the leading oral antihyperglycemic agents for type 2 diabetes treatment, which currently still constitute the most popular anti-diabetic drugs. Nevertheless, concern has arisen over the side eff ects of sulfonylureas on the cardiovascular system. Here we report that iptakalim, a novel cardiovascular ATP-sensitive potassium（ KATP） channel opener, closed rat pancreatic β-cell KATP channels and increased insulin release. Using whole-cell patch-clamp recordings, iptakalim depolarized β-cells, induced action potential fi ring and reduced pancreatic KATP channel currents. Using single-channel recordings, iptakalim reduced KATP channel open-probability independently of intracellular ATP concentrations. We demonstrated that iptakalim elevated intracellular Ca2+ concentrations and increased insulin release as revealed by fl uorescence imaging（ fura-2） and biochemical measurements, respectively. In addition, iptakalim signifi cantly inhibited the open-probability of recombinant Kir6.2/SUR1 and Kir6.2FL4A（ a traffi cking mutant of the Kir6.2） channels expressed in transfected human embryonic kidney （HEK） 293 cells. Collectively, iptakalim, a cardiovascular KATP channel opener, closes rat pancreatic β-cell KATP channels, which may result from direct inhibition of the Kir6.2 subunit. Therefore, iptakalim bi-directionally regulates KATP channels in cardiovascular and pancreatic tissues, and this unique pharmacological property suggests iptakalim could be used as a new therapeutic strategy for the treatment of type 2 diabetes with the potential benefi t in alleviating cardiac and/or vascular disorders frequently associated with diabetes. |
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| 引用 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 弘前医学. 59(Suppl.), 2007, p.S89-S100 | |||||
| 書誌情報 |
弘前医学 巻 59, 号 Supplement, p. S89-S100, 発行日 2007-11-29 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0439-1721 | |||||
| 書誌レコードID | ||||||
| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AN00211444 | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| 日本十進分類法 | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 491 | |||||
| NIIサブジェクト | ||||||
| 主題Scheme | Other | |||||
| 主題 | 基礎医学 | |||||
| 出版者 | ||||||
| 出版者 | 弘前大学大学院医学研究科・弘前医学会 | |||||
| 資源タイプ | ||||||
| 値 | Article | |||||
