{"created":"2023-05-15T09:02:45.685787+00:00","id":3628,"links":{},"metadata":{"_buckets":{"deposit":"c5d8a29d-8f4c-4d2c-858e-76556099b03c"},"_deposit":{"created_by":3,"id":"3628","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"3628"},"status":"published"},"_oai":{"id":"oai:hirosaki.repo.nii.ac.jp:00003628","sets":["557:561:643"]},"author_link":["11836","11837","11840","11841","11838","11839"],"item_3_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2007-11-29","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"Supplement","bibliographicPageEnd":"S100","bibliographicPageStart":"S89","bibliographicVolumeNumber":"59","bibliographic_titles":[{"bibliographic_title":"弘前医学"}]}]},"item_3_description_17":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_3_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Diabetes mellitus is a group of diseases characterized by high levels of blood glucose resulting from defects\nin insulin production, insulin action, or both. Diabetes patients usually have accompanying cardiovascular disorders.\nSulfonylureas have been the leading oral antihyperglycemic agents for type 2 diabetes treatment, which currently still\nconstitute the most popular anti-diabetic drugs. Nevertheless, concern has arisen over the side eff ects of sulfonylureas\non the cardiovascular system. Here we report that iptakalim, a novel cardiovascular ATP-sensitive potassium（ KATP）\nchannel opener, closed rat pancreatic β-cell KATP channels and increased insulin release. Using whole-cell patch-clamp\nrecordings, iptakalim depolarized β-cells, induced action potential fi ring and reduced pancreatic KATP channel currents.\nUsing single-channel recordings, iptakalim reduced KATP channel open-probability independently of intracellular ATP\nconcentrations. We demonstrated that iptakalim elevated intracellular Ca2+ concentrations and increased insulin release as\nrevealed by fl uorescence imaging（ fura-2） and biochemical measurements, respectively. In addition, iptakalim signifi cantly\ninhibited the open-probability of recombinant Kir6.2/SUR1 and Kir6.2FL4A（ a traffi cking mutant of the Kir6.2） channels\nexpressed in transfected human embryonic kidney （HEK） 293 cells. Collectively, iptakalim, a cardiovascular KATP\nchannel opener, closes rat pancreatic β-cell KATP channels, which may result from direct inhibition of the Kir6.2 subunit.\nTherefore, iptakalim bi-directionally regulates KATP channels in cardiovascular and pancreatic tissues, and this unique\npharmacological property suggests iptakalim could be used as a new therapeutic strategy for the treatment of type 2\ndiabetes with the potential benefi t in alleviating cardiac and/or vascular disorders frequently associated with diabetes.","subitem_description_type":"Abstract"}]},"item_3_description_7":{"attribute_name":"引用","attribute_value_mlt":[{"subitem_description":"弘前医学. 59(Suppl.), 2007, p.S89-S100","subitem_description_type":"Other"}]},"item_3_publisher_35":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"弘前大学大学院医学研究科・弘前医学会"}]},"item_3_radio_42":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_radio_item":"Article"}]},"item_3_source_id_11":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AN00211444","subitem_source_identifier_type":"NCID"}]},"item_3_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0439-1721","subitem_source_identifier_type":"ISSN"}]},"item_3_subject_19":{"attribute_name":"日本十進分類法","attribute_value_mlt":[{"subitem_subject":"491","subitem_subject_scheme":"NDC"}]},"item_3_subject_23":{"attribute_name":"NIIサブジェクト","attribute_value_mlt":[{"subitem_subject":"基礎医学","subitem_subject_scheme":"Other"}]},"item_3_text_4":{"attribute_name":"著者所属","attribute_value_mlt":[{"subitem_text_value":"Division of Clinical Research, Hirosaki National Hospital"},{"subitem_text_value":"Department of Physiology, Hirosaki University, Graduate School of Medicine"},{"subitem_text_value":"Department of Physiology and Membrane Biology, University of California, Davis, School of Medicine"},{"subitem_text_value":"Division of Neurology, Barrow Neurological Institute"},{"subitem_text_value":"Division of Neurology, Barrow Neurological Institute"},{"subitem_text_value":"Division of Neurology, Barrow Neurological Institute"}]},"item_3_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Wakui, Makoto"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Misaki, Naoko"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"Suga, Sechiko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Mao, Xia"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Lin, Yu-Fung"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Wu, Jie"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-03-13"}],"displaytype":"detail","filename":"HirosakiMedJ_59_S89.pdf","filesize":[{"value":"220.9 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"HirosakiMedJ_59_S89.pdf","url":"https://hirosaki.repo.nii.ac.jp/record/3628/files/HirosakiMedJ_59_S89.pdf"},"version_id":"e712e45d-093e-4d83-836f-eaab3ec95c44"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"iptakalim","subitem_subject_scheme":"Other"},{"subitem_subject":"K_ATP channel","subitem_subject_scheme":"Other"},{"subitem_subject":"Kir6.2","subitem_subject_scheme":"Other"},{"subitem_subject":"β-cell","subitem_subject_scheme":"Other"},{"subitem_subject":"insulin secretion","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Closure by iptakalim, a cardiovascular KATP channel opener, of rat pancreatic β-cell KATP channels and its molecular basis","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Closure by iptakalim, a cardiovascular KATP channel opener, of rat pancreatic β-cell KATP channels and its molecular basis"}]},"item_type_id":"3","owner":"3","path":["643"],"pubdate":{"attribute_name":"公開日","attribute_value":"2009-09-18"},"publish_date":"2009-09-18","publish_status":"0","recid":"3628","relation_version_is_last":true,"title":["Closure by iptakalim, a cardiovascular KATP channel opener, of rat pancreatic β-cell KATP channels and its molecular basis"],"weko_creator_id":"3","weko_shared_id":3},"updated":"2023-05-15T09:58:38.528383+00:00"}