2021/12/27 更新

写真a

ヒグチ チグサ
樋口 千草
HIGUCHI Chigusa
所属
保健管理センター 助教
職名
助教
外部リンク

研究分野

  • ライフサイエンス / 代謝、内分泌学

学歴

  • 岡山大学    

    - 2015年

      詳細を見る

    国名: 日本国

    researchmap

  • 岡山大学   Graduate School, Division of Medicine   department of nephrology, Rheumatology, Enocrinology and metabolism

    - 2015年

      詳細を見る

経歴

  • - Assistant Professor,Health Service Center,Okayama University

    2017年

      詳細を見る

  • - 岡山大学保健管理センター 助教

    2017年

      詳細を見る

所属学協会

 

論文

  • Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2)

    Koki Mise, Mariko Imamura, Satoshi Yamaguchi, Mayu Watanabe, Chigusa Higuchi, Akihiro Katayama, Satoshi Miyamoto, Haruhito A. Uchida, Atsuko Nakatsuka, Jun Eguchi, Kazuyuki Hida, Tatsuaki Nakato, Atsuhito Tone, Sanae Teshigawara, Takashi Matsuoka, Shinji Kamei, Kazutoshi Murakami, Ikki Shimizu, Katsuhiro Miyashita, Shinichiro Ando, Tomokazu Nunoue, Michihiro Yoshida, Masao Yamada, Kenichi Shikata, Jun Wada

    Frontiers in Cardiovascular Medicine   8   2021年5月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers Media SA  

    <bold>Background:</bold> Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear.

    <bold>Methods:</bold> Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease.

    <bold>Results:</bold> During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24–2.55, <italic>P</italic> = 0.002) and Calsepa [High-Man (Man2–6)]: 1.56 (1.19–2.04, <italic>P</italic> = 0.001). Common glycan binding to these lectins was high-mannose type of <italic>N</italic>-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001–0.055, <italic>P</italic> = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045–0.692, <italic>P</italic> = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively].

    <bold>Conclusion:</bold> The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal <italic>N</italic>-glycosylation occurring in patients with diabetes at higher risk of CVE.

    <bold>Trial Registration:</bold> This study was registered with the University Hospital Medical Information Network on June 26, 2012 (Clinical trial number: UMIN000011525, URL: <ext-link>https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013482</ext-link>).

    DOI: 10.3389/fcvm.2021.668059

    researchmap

  • Pemt Deficiency Ameliorates Endoplasmic Reticulum Stress in Diabetic Nephropathy 査読

    Mayu Watanabe, Atsuko Nakatsuka, Kazutoshi Murakami, Kentaro Inoue, Takahiro Terami, Chigusa Higuchi, Akihiro Katayama, Sanae Teshigawara, Jun Eguchi, Daisuke Ogawa, Eijiro Watanabe, Jun Wada, Hirofumi Makino

    PLOS ONE   9 ( 3 )   e92647   2014年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Phosphatidylethanolamine N-methyltransferase (Pemt) catalyzes the methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) mainly in the liver. Under an obese state, the upregulation of Pemt induces endoplasmic reticulum (ER) stress by increasing the PC/PE ratio in the liver. We targeted the Pemt gene in mice to explore the therapeutic impact of Pemt on the progression of diabetic nephropathy and diabetes, which was induced by the injection of streptozotocin (STZ). Although the blood glucose levels were similar in STZ-induced diabetic Pemt+/+ and Pemt-/-mice, the glomerular hypertrophy and albuminuria in Pemt-/- mice were significantly reduced. Pemt deficiency reduced the intraglomerular F4/80-positive macrophages, hydroethidine fluorescence, tubulointerstitial fibrosis and tubular atrophy. The expression of glucose-regulated protein-78 (GRP78) was enriched in the renal tubular cells in STZ-induced diabetic mice, and this was ameliorated by Pemt deficiency. In mProx24 renal proximal tubular cells, the treatment with ER-stress inducers, tunicamycin and thapsigargin, increased the expression of GRP78, which was reduced by transfection of a shRNA lentivirus for Pemt (shRNA-Pemt). The number of apoptotic cells in the renal tubules was significantly reduced in Pemt-/- diabetic mice, and shRNA-Pemt upregulated the phosphorylation of Akt and decreased the cleavage of caspase 3 and 7 in mProx24 cells. Taken together, these findings indicate that the inhibition of Pemt activity ameliorates the ER stress associated with diabetic nephropathy in a model of type 1 diabetes and corrects the functions of the three major pathways downstream of ER stress, i.e. oxidative stress, inflammation and apoptosis.

    DOI: 10.1371/journal.pone.0092647

    Web of Science

    researchmap

  • Comparison of Insulin Detemir and Insulin Glargine on Glycemic Variability in Patients with Type 1 and Type 2 Diabetes 査読

    Tone A, Iseda I, Higuchi C, Tsukamoto K, Katayama A, Matsushita Y, Hida K, Wada J, Shikata K

    Experimental and Clinical Endocrinology & Diabetes   118 ( 5 )   320 - 324   2010年

MISC

  • 学生健康診断における尿糖陽性者への2次検診についての検討

    樋口千草, 和田淳, 影山真希, 山際陽子, 岡香織, 黒木清美, 河原宏子, 二宮崇, 清水幸登, 大西勝, 岩﨑良章

    CAMPUS HEALTH   56 ( 1 )   271   2019年3月

     詳細を見る

    担当区分:筆頭著者   記述言語:日本語  

    researchmap

  • 在校生健康診断における尿糖陽性者の検討

    第47回中国・四国大学保健管理研究集会報告書   2017年

     詳細を見る

  • Identification of Circulating miR-101, miR-375 and miR-802 as Biomarkers for Type 2 Diabetes

    Chigusa Higuchi, Atsuko Nakatsuka, Jun Eguchi, Sanae Teshigawara, Motoko Kanzaki, Akihiro Katayama, Satoshi Yamaguchi, Naoto Takahashi, Kazutoshi Murakami, Daisuke Ogawa, Sakiko Sasaki, Hirofumi Makino, Jun Wada

    METABOLISM-CLINICAL AND EXPERIMENTAL   64 ( 4 )   489 - 497   2015年4月

     詳細を見る

    記述言語:英語   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Purpose. The unique circulating microRNAs (miRNAs) observed in patients with type 2 diabetes (T2D) are candidates as new biomarkers and therapeutic targets. In order to identify circulating miRNAs relevant to the disease process in case of type 2 diabetes, we performed the Illumina sequencing of miRNAs derived from the serum, liver and epididymal white adipose tissue (WAT) of diet-induced obese male C57BL/6J mice.
    Basic Procedures. We selected four miRNAs, miR-101, miR-335, miR-375, and miR-802, which are increased in the sera and tissues of obese mice, and measured the serum levels of miRNAs in T2D and subjects with normal glucose tolerance (NGT).
    Main Findings. The serum concentrations of miRNAs, log10miR-101, log(10)miR-375, and log(10)miR-802, were significantly increased in the T2D patients compared with NGT subjects (1.41 +/- 2.01 u.s. -0.57 +/- 1.05 (P = 1.36 x 10(-5)), 0.20 +/- 0.58 v.s. 0.038 +/- 1.00 (P = 3.06 x 10(-6)), and 2.45 +/- 1.27 u.s. 0.97 +/- 0.98 (P = 0.014), respectively). The log(10)miR-335 values did not demonstrate any significant differences between the T2D and NGT groups (-1.08 +/- 1.35 v.s. 0.38 +/- 1.21 (P = 0.25)). According to the stepwise regression analysis, the HbA1c was an independent predictor of miR-101. Regarding the serum miR-802 levels, eGFR, HbA1c and HDL-C values were identified as significant determinants.
    Principal Conclusions. The present findings demonstrated that the circulating miR-101, miR-375 and miR-802 levels are significantly increased in T2D patients versus NGT subjects and they may become the new biomarkers for type 2 diabetes. (C) 2015 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.metabol.2014.12.003

    Web of Science

    researchmap