Updated on 2024/09/20

写真a

 
Inagaki Kyoko
 
Affiliation
Nippon Medical School Hospital, Department of Endocrinology, Diabetes and Metabolism, Senior Assistant Professor
Title
Senior Assistant Professor
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Degree

  • 医学博士 ( 日本医科大学 )

Research Areas

  • Life Science / Metabolism and endocrinology

Research History

  • Nippon Medical School   Senior Assistant Professor

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Papers

  • HLA investigation in ICI-induced T1D and isolated ACTH deficiency including meta-analysis. International journal

    Mayo Ono, Mototsugu Nagao, Haruki Takeuchi, Etsuya Fukunaga, Tomoko Nagamine, Kyoko Inagaki, Izumi Fukuda, Masato Iwabu

    European journal of endocrinology   191 ( 1 )   9 - 16   2024.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    OBJECTIVE: Widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment has led to an increase in the number of reported cases of immunotherapy-related endocrinopathies. This study aimed to analyze and compare human leukocyte antigen (HLA) signatures associated with ICI-induced type 1 diabetes (ICI-T1D) and isolated adrenocorticotropic hormone deficiency (ICI-IAD) in patients with both conditions. METHODS: HLA signatures were examined for their frequencies of occurrence in 22 patients with ICI-T1D without concurrent IAD, including 16 patients from nationwide reports (ICI-T1D group) and 14 patients with ICI-IAD without concurrent T1D (ICI-IAD group). The HLA signatures were also compared for their respective frequencies in 11 patients with ICI-T1D and ICI-IAD, including eight from nationwide reports (ICI-T1D/IAD group). RESULTS: In the ICI-T1D group, HLA-DRB1*09:01-DQB1*03:03 and DQA1*03:02, which are in linkage disequilibrium with DRB1*09:01-DQB1*03:03 and DRB1*13:02-DQB1*06:04, were susceptible to ICI-T1D, whereas DRB1*15:02-DQB1*06:01 was protective against ICI-T1D. In the ICI-IAD group, DPB1*09:01, C*12:02-B*52:01, and DRB1*15:02-DRB1*06:01, which are in strong linkage disequilibrium, were associated with susceptibility to ICI-IAD. Moreover, DRB1*15:02-DRB1*06:01 was not detected in the ICI-T1D/IAD group. CONCLUSIONS: This study revealed specific HLA signatures associated with ICI-T1D and ICI-IAD. Moreover, HLA-DRB1*15:02-DRB1*06:01, an ICI-IAD-susceptible HLA haplotype, coincides with the ICI-T1D-protective HLA haplotype, suggesting that the presence of DRB1*15:02-DRB1*06:01 may protect against the co-occurrence of T1D in patients with ICI-IAD.

    DOI: 10.1093/ejendo/lvae081

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  • Ipragliflozin and sitagliptin differentially affect lipid and apolipoprotein profiles in type 2 diabetes: the SUCRE study. International journal

    Mototsugu Nagao, Jun Sasaki, Kyoko Tanimura-Inagaki, Ichiro Sakuma, Hitoshi Sugihara, Shinichi Oikawa

    Cardiovascular diabetology   23 ( 1 )   56 - 56   2024.2

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    BACKGROUND: SGLT2 inhibitors and DPP4 inhibitors have been suggested to affect lipid metabolism. However, there are few randomized controlled trials comparing the effects on the lipid metabolism between the two types of antidiabetic drugs. The SUCRE study (UMIN ID: 000018084) was designed to compare the effects of ipragliflozin and sitagliptin on serum lipid and apolipoprotein profiles and other clinical parameters. METHODS: This is a multicenter, open-label, randomized, controlled trial. Patients with type 2 diabetes (20-74 years old) with HbA1c levels of 7.0-10.5% and serum triglyceride levels of 120-399 mg/dL (1.35-4.50 mmol/L) on diet and/or oral hypoglycemic agents were enrolled. Subjects were randomized to treatment with ipragliflozin (50 mg/day, n = 77) or sitagliptin (50 mg/day, n = 83). Laboratory measurements were performed at 0, 1, 3, and 6 months of treatment. RESULTS: Ipragliflozin and sitagliptin reduced fasting plasma glucose, glycoalbumin, and HbA1c almost equally. Ipragliflozin increased HDL-C and decreased apo E. Sitagliptin decreased TG, apo B48, CII, and CIII, but increased LDL-C. The between-treatment differences were significant for HDL-C (P = 0.02) and apo B48 (P = 0.006), and nearly significant for apo A1 (P = 0.06). In addition, ipragliflozin reduced body weight, blood pressure, serum liver enzymes, uric acid, and leptin, and increased serum ketones compared with sitagliptin. CONCLUSIONS: While ipragliflozin and sitagliptin showed similar effects on glycemic parameters, the effects on serum lipid and apolipoprotein profiles were different. Ipragliflozin may have an anti-atherogenic effect through modulation of HDL-C and apo E compared to sitagliptin through TG and apo B48, CII, and CIII in patients with type 2 diabetes.

    DOI: 10.1186/s12933-024-02149-7

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  • Crucial role of iron in epigenetic rewriting during adipocyte differentiation mediated by JMJD1A and TET2 activity Reviewed International journal

    Tomohiro Suzuki, Tetsuro Komatsu, Hiroshi Shibata, Akiko Tanioka, Diana Vargas, Reika Kawabata-Iwakawa, Fumihito Miura, Shinnosuke Masuda, Mayuko Hayashi, Kyoko Tanimura-Inagaki, Sumiyo Morita, Junki Kohmaru, Koji Adachi, Masayuki Tobo, Hideru Obinata, Tasuku Hirayama, Hiroshi Kimura, Juro Sakai, Hideko Nagasawa, Hideyuki Itabashi, Izuho Hatada, Takashi Ito, Takeshi Inagaki

    Nucleic Acids Research   51 ( 12 )   6120 - 6142   2023.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    Abstract

    Iron metabolism is closely associated with the pathogenesis of obesity. However, the mechanism of the iron-dependent regulation of adipocyte differentiation remains unclear. Here, we show that iron is essential for rewriting of epigenetic marks during adipocyte differentiation. Iron supply through lysosome-mediated ferritinophagy was found to be crucial during the early stage of adipocyte differentiation, and iron deficiency during this period suppressed subsequent terminal differentiation. This was associated with demethylation of both repressive histone marks and DNA in the genomic regions of adipocyte differentiation-associated genes, including Pparg, which encodes PPARγ, the master regulator of adipocyte differentiation. In addition, we identified several epigenetic demethylases to be responsible for iron-dependent adipocyte differentiation, with the histone demethylase jumonji domain-containing 1A and the DNA demethylase ten-eleven translocation 2 as the major enzymes. The interrelationship between repressive histone marks and DNA methylation was indicated by an integrated genome-wide association analysis, and was also supported by the findings that both histone and DNA demethylation were suppressed by either the inhibition of lysosomal ferritin flux or the knockdown of iron chaperone poly(rC)-binding protein 2. In summary, epigenetic regulations through iron-dependent control of epigenetic enzyme activities play an important role in the organized gene expression mechanisms of adipogenesis.

    DOI: 10.1093/nar/gkad342

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  • 家族性高コレステロール血症におけるスタチン不耐症と甲状腺機能の関係

    稲垣 恭子, 山口 祐司, 福田 いずみ, 岩部 真人

    日本内分泌学会雑誌   99 ( 1 )   343 - 343   2023.5

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  • Early effects of insulin therapy on cholesterol synthesis and absorption markers in patients with type 2 diabetes

    Yuji Yamaguchi, Kyoko Tanimura-Inagaki, Izumi Fukuda, Hitoshi Sugihara, Shinichi Oikawa

    Clinical Nutrition Open Science   48   64 - 74   2023.4

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    Background & aim: Metabolic abnormalities in type 2 diabetes affect the production and the clearance of plasma lipoproteins. Although the improvement of low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol levels are important targets in diabetes, it is not established how changes occur in the production and clearance of plasma lipoproteins in the treatment of diabetes. Serum non-cholesterol sterols are introduced as practical markers to assess endogenous cholesterol synthesis and intestinal cholesterol absorption. This study aimed to investigate the effects of insulin therapy on cholesterol synthesis and absorption markers in patients with type 2 diabetes. Methods: This was a single-center, prospective, 2-week, longitudinal pilot study. Patients with type 2 diabetes who were admitted to start insulin therapy without using lipid-lowering agents were recruited. On the day of hospitalization, the patients discontinued all oral hypoglycemic agents and started with basal-bolus insulin therapy. Cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) markers were assessed at baseline and after 2 weeks of insulin treatment. Results: In eighteen subjects, the mean age of the patients was 56 ± 10 years (mean ± SD). At baseline, body mass index was 24.3 ± 5.0 kg/m2, and HbA1c was 11.6 ± 1.7%. After 2 weeks of insulin therapy, total cholesterol (from 205 ± 48 to 184 ± 43 mg/dL, p = 0.004), lathosterol (from 2.6 ± 1.3 to 2.0 ± 0.7 μg/mL, p = 0.001), campesterol (from 4.3 ± 2.7 to 3.0 ± 2.1 μg/mL, p < 0.0001), and sitosterol (from 2.4 ± 1.6 to 1.7 ± 1.4 μg/mL, p < 0.0001) were significantly decreased, and cholestanol (from 2.5 ± 1.0 to 2.3 ± 0.8 μg/mL, p = 0.05) tended to decrease. Conclusion: This study showed that insulin therapy reduces cholesterol synthesis and absorption markers in patients with type 2 diabetes hospitalized within 2 weeks. The decrease in cholesterol synthesis and absorption seems to be useful for improving lipid metabolism and reducing the risk of atherosclerosis. Further randomized controlled studies are required to confirm the efficacy of insulin therapy for cholesterol synthesis and absorption markers.

    DOI: 10.1016/j.nutos.2023.03.001

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Misc.

  • 【ココが変わった 肥満症診療の最前線】肥満症の診療 肥満の健康障害

    福永 悦也, 稲垣 恭子

    診断と治療   112 ( 2 )   153 - 161   2024.2

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    Language:Japanese   Publisher:(株)診断と治療社  

    <文献概要>Headline ・単なる体重が重い状態の「肥満」と,過体重による健康障害を合併する「肥満症」は異なる概念である.・減量による予後改善効果が期待できる健康障害を有する「肥満症」は,積極的な減量治療の対象である.・肥満症に伴う健康障害の多くは日常臨床で遭遇するものであり,常にこれらと肥満の関連を念頭におくことが求められる.

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J00697&link_issn=&doc_id=20240219090009&doc_link_id=10.34433%2Fdt.0000000579&url=https%3A%2F%2Fdoi.org%2F10.34433%2Fdt.0000000579&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 非小細胞肺癌に対してニボルマブを投与した後に両側副腎転移による原発性副腎皮質機能低下症をきたし、副腎クリーゼに至った一例

    井上 祥子, 山口 祐司, 富山 敬子, 梁井 香那子, 大野 万葉, 周東 佑樹, 長尾 元嗣, 稲垣 恭子, 福田 いずみ, 岩部 真人

    日本内分泌学会雑誌   99 ( 4 )   905 - 905   2024.1

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  • 妊娠中にlanreotideの投与を要したTSH産生PitNETの一例

    宮澤 未祐, 山口 祐司, 中山 裕香子, 柴山 雅行, 羽田 幹子, 築山 敦, 長峯 朋子, 石坂 栄太郎, 長尾 元嗣, 井野元 智恵, 稲垣 恭子, 田原 重志, 福田 いずみ, 長村 義之, 岩部 真人

    日本内分泌学会雑誌   99 ( 2 )   589 - 589   2023.10

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  • 妊娠中にlanreotideの投与を要したTSH産生PitNETの一例

    宮澤 未祐, 山口 祐司, 中山 裕香子, 柴山 雅行, 羽田 幹子, 築山 敦, 長峯 朋子, 石坂 栄太郎, 長尾 元嗣, 井野元 智恵, 稲垣 恭子, 田原 重志, 福田 いずみ, 長村 義之, 岩部 真人

    日本内分泌学会雑誌   99 ( 2 )   589 - 589   2023.10

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  • 肥満症、糖尿病、脂質異常症 改訂されたガイドラインと診療トピックスについて

    稲垣 恭子

    日本病院総合診療医学会雑誌   19 ( 臨増2 )   65 - 65   2023.8

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Presentations

  • 妊娠中にlanreotideの投与を要したTSH産生PitNETの一例

    宮澤 未祐, 山口 祐司, 中山 裕香子, 柴山 雅行, 羽田 幹子, 築山 敦, 長峯 朋子, 石坂 栄太郎, 長尾 元嗣, 井野元 智恵, 稲垣 恭子, 田原 重志, 福田 いずみ, 長村 義之, 岩部 真人

    日本内分泌学会雑誌  2023.10  (一社)日本内分泌学会

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    Event date: 2023.10

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  • 家族性高コレステロール血症におけるスタチン不耐症と甲状腺機能の関係

    稲垣 恭子, 山口 祐司, 福田 いずみ, 岩部 真人

    日本内分泌学会雑誌  2023.5  (一社)日本内分泌学会

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    Event date: 2023.5

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  • immature PIT1-lineage PitNETによる若年性先端巨大症の一例

    富山 敬子, 田原 重志, 長峯 朋子, 長尾 元嗣, 稲垣 恭子, 寺崎 美佳, 福田 いずみ, 岩部 真人

    日本内分泌学会雑誌  2023.5  (一社)日本内分泌学会

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    Event date: 2023.5

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  • 迅速なインスリノーマの診断に向けた規定因子の解析

    小林 俊介, 長尾 元嗣, 稲垣 恭子, 福田 いずみ, 岩部 真人

    日本医科大学医学会雑誌  2022.12  日本医科大学医学会

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    Event date: 2022.12

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  • 大腿骨頸部骨折に甲状腺クリーゼを合併した一例

    宮澤 未祐, 小林 俊介, 川久保 瑠美, 長尾 元嗣, 稲垣 恭子, 福田 いずみ, 杉原 仁, 岩部 真人

    日本内分泌学会雑誌  2022.10  (一社)日本内分泌学会

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    Event date: 2022.10

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Research Projects

  • 新規ヒストン修飾解析手法を用いた白色脂肪細胞分化過程のエピゲノム変化の解析

    Grant number:21K06282  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    稲垣 恭子

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    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

    肥満症克服は現代社会の重要な課題であり脂肪蓄積メカニズムの解明が必要である。環境因子は細胞に記憶され、遺伝子の塩基配列に依存せず遺伝子発現を調節する機構(エピゲノム)を調節する。DNAが巻き付いているヒストン修飾はDNA発現を調節する。これまでエピゲノム研究はヒストン修飾部位への抗体を用いた手法が用いられ、抗体の質に依存する問題点があった。本研究では抗体を必要としない質量分析法を改良し網羅的ヒストン修飾解析の手法を確立し、脂肪細胞分化におけるヒストン修飾の組み合わせの意義を解明することを目的としている。質量分析を用いた脂肪細胞分化過程の網羅的ヒストン修飾同定の報告は過去になく、脂肪蓄積におけるエピゲノム機構の解明は、肥満症治療の創薬への一助となる可能性がある。
    本研究では、質量分析の前処置薬である無水プロピオニルを同位体試薬13C無水プロピオン酸とすることで、従来同定できないヒストンモノメチル化同定が可能となると考え基礎実験を行った。3T3-L1前駆細胞に対し、分化誘導培地により分化を誘導し、2日後インスリンのみを含む培地、4日目以後通常培地で培養し、8日間をかけて3T3-L1脂肪細胞に分化させ、分化前、8日後の3T3-L1細胞からヒストンを精製し、質量分析前措置として通常の無水プロピオン酸処理と、改良法である無水プロピオン酸同位体標識試薬(13C無水プロピオン酸)処理をそれぞれ行い、トリプシン消化、オービトラップ質量分析計にかけ、データベース検索エンジンMascotによりヒストン修飾同定を行い、13C無水プロピオン酸処理によりモノメチル化が同定されることを確認した。これより分化前、1日、2日、4日、8日後の白色脂肪細胞分化細胞のヒストンを、無水プロピオン酸、および13C無水プロピオン酸処理を行い、ヒストンの脂肪分化における経時的修飾変化の基礎データを得ることができた。

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