{"created":"2023-06-19T10:29:33.127121+00:00","id":1659,"links":{},"metadata":{"_buckets":{"deposit":"057990ba-43d6-4e64-b18c-89e412f81e85"},"_deposit":{"created_by":31,"id":"1659","owners":[31],"pid":{"revision_id":0,"type":"depid","value":"1659"},"status":"published"},"_oai":{"id":"oai:kwmed.repo.nii.ac.jp:00001659","sets":["1709617079800:35:321:560"]},"author_link":["111206","111207"],"item_1694495855422":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_type":"VoR"}]},"item_3_biblio_info_12":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2014","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"2","bibliographicPageEnd":"88","bibliographicPageStart":"77","bibliographicVolumeNumber":"40","bibliographic_titles":[{"bibliographic_title":"川崎医学会誌","bibliographic_titleLang":"ja"},{"bibliographic_title":"Kawasaki medical journal","bibliographic_titleLang":"en"}]}]},"item_3_description_8":{"attribute_name":"記事種別(日)","attribute_value_mlt":[{"subitem_description":"原著","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_3_identifier_14":{"attribute_name":"URL","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"http://igakkai.kms-igakkai.com/wp/wp-content/uploads/2014/KMJ-J40(2)77.pdf"}]},"item_3_relation_20":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.11482/KMJ-J40(2)77","subitem_relation_type_select":"DOI"}}]},"item_3_source_id_1":{"attribute_name":"雑誌書誌ID","attribute_value_mlt":[{"subitem_source_identifier":"AN00045593","subitem_source_identifier_type":"NCID"},{"subitem_source_identifier":"AN12940574","subitem_source_identifier_type":"NCID"}]},"item_3_source_id_19":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0386-5924","subitem_source_identifier_type":"PISSN"},{"subitem_source_identifier":"2758-089X","subitem_source_identifier_type":"EISSN"}]},"item_3_text_6":{"attribute_name":"著者所属(日)","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"川崎医科大学糖尿病・代謝・内分泌内科学"}]},"item_3_text_7":{"attribute_name":"著者所属(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School"}]},"item_3_textarea_10":{"attribute_name":"抄録(日)","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"2型糖尿病の病態進展を抑制する上で,膵β細胞機能保持は極めて重要な課題である.PPARγ作動薬やインクレチン薬は糖尿病モデル動物のβ細胞機能保護に働くが,殆どが発症早期の検討であり,病態進展期での検討は十分でない.本研究では肥満糖尿病モデルdb/dbマウスを用いて,病態の進展がPioglitazone(PIO)とLiraglutide(LIRA)によるβ細胞保護効果に及ぼす影響を検討した.早期モデルに7週齢を,進行モデルには16週齢を用い,対照(CTL),PIO,LIRA,併用の4群に分けた.代謝改善による影響を排除し,薬剤の直接的なβ細胞への効果を検討するため2日間介入とした.またlaser capture microdissection法を用いて,膵島コア領域の遺伝子発現解析を行った.早期モデルのLIRA群,進行期の併用群で空腹時血糖の改善傾向をみたが,インスリン値に有意な変動はなかった.進行期モデルでInsulin,GLP-1受容体遺伝子発現が低下した.分化・増殖に関わるPdx1,NeuroD,ERK1は早期モデルのみ上昇がみられ,インスリン転写因子Pdx1,NeuroDも同様であった.一方,アポトーシス関連遺伝子Caspase3,Bcl2の発現は,両モデルでアポトーシス抑制方向に変動した.これらの効果は併用群でより顕著で統計学的に有意であった.脂質合成,炎症,酸化ストレス,小胞体ストレス関連遺伝子発現は,両モデルで変動しなかった.以上より病態早期ではPIO,LIRAは分化・増殖促進とアポトーシス抑制によるβ細胞保護効果を発揮し,進行期ではその効果は限定的であること,その効果は膵への直接的作用であることが明らかになった.本研究成果は早期からの薬剤介入が糖尿病の病態進展抑制に有効であることを強く示唆する."}]},"item_3_textarea_11":{"attribute_name":"抄録(英)","attribute_value_mlt":[{"subitem_textarea_language":"en","subitem_textarea_value":"We compared the protective effects of pioglitazone, PPARγ agonist, and/or liraglutide, GLP-1 receptor agonist, on pancreatic β-cells between early and advanced stage of diabetes. Male db/db mice were treated with pioglitazone (PIO) and/or liraglutide (LIRA) for 2 days in an early stage (7 weeks of age) and advanced stage of diabetes (16 weeks of age). We performed biochemical analysis and examined gene expression profiles after such treatment in the early and advanced stage. LIRA and PIO+LIRA treatment ameliorated fasting hyperglycemia in the early stage model, and only PIO+LIRA showed the same effect in the advanced stage model. Fasting serum insulin levels were not different among 4 groups in both the early and advanced stage models. Insulin and GLP-1receptor mRNA levels were markedly reduced in the advanced stage compared with those in the early stage. Gene expressions of insulin gene transcription factors (Pdx1 and NeuroD) were significantly up-regulated by PIO and/or LIRA in the early stage, but not in the advanced stage. Cell proliferation-related factor ERK1 gene expression was also up-regulated only in the early stage by drug intervention. By contrast, in both stages, pro-apoptotic factor caspase3 mRNA level was suppressed and anti-apoptotic factor Bcl-2 level was up-regulated by drug intervention. These effects on gene expressions were statistically significant only in the PIO+LIRA treatment group. Gene expression levels of various factors related with lipid synthesis, fibrosis, oxidative stress and endoplasmic reticulum stress were not changed by drug intervention. The present results demonstrated that pioglitazone and liraglutide showed the protective effects on pancreatic β-cells in an early stage of diabetes by stimulating cell differentiation/ proliferation and suppressing cell apoptosis. These effects were limited in an advanced stage of disease. Our results strongly suggest that a pharmacological intervention from an early stage of diabetes is more effective to preserve the β-cell mass and function."}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"木村, 友彦","creatorNameLang":"ja"},{"creatorName":"キムラ, トモヒコ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Kimura, Tomohiko","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-01-23"}],"displaytype":"detail","filename":"KJ00009576239.pdf","filesize":[{"value":"855.2 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"KJ00009576239.pdf","objectType":"fulltext","url":"https://kwmed.repo.nii.ac.jp/record/1659/files/KJ00009576239.pdf"},"version_id":"336e5e44-2c07-48a8-ac0f-7f5919fc7593"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"ピオグリタゾン","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"リラグルチド","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"膵β細胞","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"糖尿病の病態進展過程","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"Pioglitazone","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Liraglutide","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Pancreatic β-cells","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Progression of diabetic morbidity","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"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":"糖尿病病態進展が抗糖尿病薬による膵β細胞保護効果に及ぼす影響-糖尿病モデルdb/dbマウスへのピオグリタゾン,リラグルチド短期介入での検討-","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"糖尿病病態進展が抗糖尿病薬による膵β細胞保護効果に及ぼす影響-糖尿病モデルdb/dbマウスへのピオグリタゾン,リラグルチド短期介入での検討-","subitem_title_language":"ja"},{"subitem_title":"The molecular mechanism by which the short-term intervention of anti-diabetic drugs preserves pancreatic β-cells in db/db mice : comparison of their straightforward effects between early and advanced stage of diabetes","subitem_title_language":"en"}]},"item_type_id":"3","owner":"31","path":["560"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2017-01-23"},"publish_date":"2017-01-23","publish_status":"0","recid":"1659","relation_version_is_last":true,"title":["糖尿病病態進展が抗糖尿病薬による膵β細胞保護効果に及ぼす影響-糖尿病モデルdb/dbマウスへのピオグリタゾン,リラグルチド短期介入での検討-"],"weko_creator_id":"31","weko_shared_id":-1},"updated":"2023-10-11T03:04:48.843727+00:00"}