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KAKEN_16K19546seika.pdf
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腸管免疫制御による高脂肪食インスリン抵抗性発症予防
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チョウカン メンエキ セイギョ ニ ヨル コウシボウショク インスリン テイコウセイ ハツショウ ヨボウ
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Chōkan meneki seigyo ni yoru kōshibōshoku insurin teikōsei hatsushō yobō
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The physiological roles of intestinal immunity in high fat diet induced insulin resistance
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川野, 義長
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カワノ, ヨシナガ
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Kawano, Yoshinaga
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慶應義塾大学・医学部(信濃町)・助教
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Research team head
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科研費研究者番号 : 80571463
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伊藤, 裕
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イトウ, ヒロシ
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Ito, Hiroshi
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慶應義塾大学・医学部(信濃町)・教授
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Research team member
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科研費研究者番号 : 40252457
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中江, 淳
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ナカエ, ジュン
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Nakae, Jun
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慶應義塾大学・医学部(信濃町)・准教授
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Research team member
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科研費研究者番号 : 00344573
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2018
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科学研究費補助金研究成果報告書
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2017
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| Abstract |
食事や腸内細菌と密接に関わる, 腸管免疫特に腸管樹状細胞や腸管CD4+T細胞に着目して, 新規の糖・エネルギー代謝制御メカニズムを検討した。腸管樹状細胞Nlrp10と腸管T細胞Foxoの機能解析を行うため, 樹状細胞特異的Nlrp10欠損マウスとCD4細胞特異的Foxo1Foxo3遺伝子改変マウスを作製し代謝表現型を解析した。樹状細胞特異的Nlrp10欠損マウスは, 高脂肪食負荷に伴い耐糖能が悪化し, CD4細胞特異的Foxo1Foxo3遺伝子改変マウスは高脂肪食負荷に伴い耐糖能が改善した。今後, 樹状細胞Nlrp10およびCD4+T細胞Foxoの標的遺伝子およびその制御メカニズムの検討を続ける。
Foxo1 is important in regulating glucose and energy homeostasis, but little is known about the roles in intestinal T cell under HFD. We generated CD4 T cell specific Foxo1 double Foxo3 hetero-KO(T-QKO) mice, Insulin sensitivity of T-QKO mice was significantly improved compared with control mice. Gene expression of Il4 and Il13 in Peyer's patch from T-QKO were significantly increased compared with control mice. These data suggested that Foxo activation of CD4+Tcell may deteriorate HFD induced insulin resistance. Nlrp10 is known as NLR family and it has been reported that Nlrp10 in Dendritic Cell play important roles in T cell activation and induction of Acquired Immunity.Insulin sensitivity of CD11cNlrp10KO was significantly deteriorated compared with control mice. Gene expression of Foxo3 and Il17 in colon from Nlrp10KO were decreased compared with HFD control mice. These data suggested that Nlrp10 in Dendritic cell may play protective roles in HFD induced insulin resistance.
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研究種目 : 若手研究(B)
研究期間 : 2016～2017
課題番号 : 16K19546
研究分野 : インスリン抵抗性
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