2025/06/01 更新

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写真a

オリメ　カズキ
折目 和基
Kazuki Orime
所属
附属市民総合医療センター 内分泌・糖尿病内科 講師
職名
講師
外部リンク

学位

  • 医学博士 （ 横浜市立大学 ）

研究キーワード

  • インスリン

  • 糖尿病

  • 膵β細胞

  • 肝臓

研究分野

  • ライフサイエンス / 代謝、内分泌学  / 糖尿病学・内分泌学・代謝学

学歴

  • 横浜市立大学   医学研究科

    2009年4月 - 2013年3月

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  • 横浜市立大学   医学部   医学科

    2000年4月 - 2006年3月

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経歴

  • 横浜市立大学 附属市民総合医療センター   内分泌・糖尿病内科   部長   講師

    2023年4月 - 現在

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  • 横浜市立大学 附属市民総合医療センター   内分泌・糖尿病内科   助教

    2021年4月 - 2023年3月

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  • 横浜市立大学   トランスレーショナルリサーチ推進室   特任助教

    2019年4月 - 2021年3月

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  • Harvard Medical School, Joslin Diabetes Center   Islet Cell & Regenerative Biology   Research Fellow

    2016年5月 - 2019年3月

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  • 横浜市立大学   内分泌・糖尿病内科   助教

    2015年4月 - 2016年3月

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所属学協会

▼全件表示

委員歴

  • 日本糖尿病医療学学会   評議員  

    2023年 - 現在   

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  • 社会保険診療報酬支払基金   審査委員  

    2023年 - 現在   

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  • 日本糖尿病学会   評議員  

    2023年 - 現在   

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論文

  • Type 1 Diabetes Mellitus with Diabetic Ketoacidosis Presenting with Transient Severe Fatty Liver and Subsequent Liver Dysfunction.

    Takayuki Suzuki, Kazuki Orime, Ryoichi Akamatsu, Tomoaki Akiyama, Tadashi Yamakawa, Yasuo Terauchi

    Internal medicine (Tokyo, Japan)   63 ( 24 )   3339 - 3344   2024年12月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Patients often present with severe fatty liver (FL) due to insulin deficiency at the onset of diabetic ketoacidosis (DKA). On the other hand, glycogenic hepatopathy (GH) is a possible cause of liver dysfunction in patients with DKA. We herein report a case of type 1 diabetes mellitus with severe FL at the onset of DKA, who demonstrated subsequent marked liver dysfunction after achieving an improvement of FL. As liver dysfunction persisted even after the FL improved, GH was suspected to be the cause of liver dysfunction. FL and GH have different prognoses and should therefore be differentiated using imaging studies and biopsies.

    DOI： 10.2169/internalmedicine.3488-24

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  • Efficacy of StepAdd, a Personalized mHealth Intervention Based on Social Cognitive Theory to Increase Physical Activity Among Patients With Type 2 Diabetes Mellitus: Protocol for a Randomized Controlled Trial. 国際誌

    Kayo Waki, Yuya Tsurutani, Hironori Waki, Syunpei Enomoto, Kosuke Kashiwabara, Akira Fujiwara, Kazuki Orime, Sho Kinguchi, Toshimasa Yamauchi, Nobuhito Hirawa, Kouichi Tamura, Yasuo Terauchi, Masaomi Nangaku, Kazuhiko Ohe

    JMIR research protocols   13   e53514   2024年2月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    BACKGROUND: Increasing physical activity improves glycemic control in patients with type 2 diabetes (T2D). Mobile health (mHealth) interventions have been proven to increase exercise, but engagement often fades with time. As the use of health behavior theory in mHealth design can increase effectiveness, we developed StepAdd, an mHealth intervention based on the constructs of social cognitive theory (SCT). StepAdd improves exercise behavior self-efficacy and self-regulation through the use of goal-setting, barrier-identifying, and barrier-coping strategies, as well as automatic feedback functions. A single-arm pilot study of StepAdd among 33 patients with T2D showed a large increase in step count (mean change of 4714, SD 3638 daily steps or +86.7%), along with strong improvements in BMI (mean change of -0.3 kg/m2) and hemoglobin A1c level (mean change of -0.79 percentage points). OBJECTIVE: In this study, we aim to investigate the efficacy and safety of StepAdd, an mHealth exercise support system for patients with T2D, via a large, long, and controlled follow-up to the pilot study. METHODS: This is a randomized, open-label, multicenter study targeting 160 patients with T2D from 5 institutions in Japan with a 24-week intervention. The intervention group will record daily step counts, body weight, and blood pressure using the SCT-based mobile app, StepAdd, and receive feedback about these measurements. In addition, they will set weekly step count goals, identify personal barriers to walking, and define strategies to overcome these barriers. The control group will record daily step counts, body weight, and blood pressure using a non-SCT-based placebo app. Both groups will receive monthly consultations with a physician who will advise patients regarding lifestyle modifications and use of the app. The 24-week intervention period will be followed by a 12-week observational period to investigate the sustainability of the intervention's effects. The primary outcome is between-group difference in the change in hemoglobin A1c values at 24 weeks. The secondary outcomes include other health measures, measurements of steps, measurements of other behavior changes, and assessments of app use. The trial began in January 2023 and is intended to be completed in December 2025. RESULTS: As of September 5, 2023, we had recruited 44 patients. We expect the trial to be completed by October 8, 2025, with the follow-up observation period being completed by December 31, 2025. CONCLUSIONS: This trial will provide important evidence about the efficacy of an SCT-based mHealth intervention in improving physical activities and glycemic control in patients with T2D. If this study proves the intervention to be effective and safe, it could be a key step toward the integration of mHealth as part of the standard treatment received by patients with T2D in Japan. TRIAL REGISTRATION: Japan Registry of Clinical Trials (JRCT) jRCT2032220603; https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2032220603. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53514.

    DOI： 10.2196/53514

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  • Effects of hybrid closed-loop system on glycemic control and psychological aspects in persons with type 1 diabetes treated with sensor-augmented pump: A prospective single-center observational study.

    Tomoaki Akiyama, Tadashi Yamakawa, Kazuki Orime, Masahiro Ichikawa, Marina Harada, Takumi Netsu, Ryoichi Akamatsu, Keita Nakamura, Satoru Shinoda, Yasuo Terauchi

    Journal of diabetes investigation   2023年11月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    AIMS/INTRODUCTION: This study evaluated the effects of the Medtronic MiniMed 770G hybrid closed-loop system on glycemic control and psychological aspects in persons with type 1 diabetes mellitus. MATERIALS AND METHODS: This 3-month prospective observational study included 22 participants with type 1 diabetes mellitus who used the Medtronic MiniMed 640G predictive low-glucose suspend system and were switched to the 770G system. Time in the range of 70-180 mg/dL and glycated hemoglobin levels were evaluated; satisfaction, emotional distress and quality of life were assessed using self-reported questionnaires, including the Diabetes Treatment Satisfaction Questionnaire Status, Problem Area in Diabetes and Diabetes Therapy-Related Quality of Life. RESULTS: Time in the range of 70-180 mg/dL increased (63.5 ± 13.4 to 73.0 ± 10.9% [mean ± standard deviation], P = 0.0010), and time above the range of 181-250 mg/dL decreased (26.9 ± 8.9 to 19.6 ± 7.1%, P < 0.0005). Glycated hemoglobin levels decreased (7.7 ± 1.0 to 7.2 ± 0.8%, P = 0.0021). The percentage of participants with time below the range of 54-69 mg/dL <4% of readings increased from 91% to 100% (P < 0.0005). No significant changes were detected in the satisfaction, emotional distress and quality of life levels, but increased sensor calibration might be related to worsened emotional distress and quality of life. CONCLUSIONS: The hybrid closed-loop system decreased hyperglycemia and minimized hypoglycemia, but did not improve psychological aspects compared with the predictive low-glucose suspend system, probably because sensor calibration was increased.

    DOI： 10.1111/jdi.14103

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  • Sleep duration and food intake in people with type 2 diabetes mellitus and factors affecting confectionery intake.

    Tomoaki Akiyama, Tadashi Yamakawa, Kazuki Orime, Jun Suzuki, Rika Sakamoto, Minori Matsuura-Shinoda, Erina Shigematsu, Kenichiro Takahashi, Mizuki Kaneshiro, Taro Asakura, Shunichi Tanaka, Takehiro Kawata, Yoshihiko Yamada, Tetsuo Isozaki, Atsushi Takahashi, Uru Nezu Osada, Kazuaki Kadonosono, Yasuo Terauchi

    Journal of diabetes investigation   14 ( 5 )   716 - 724   2023年2月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    AIMS/INTRODUCTION: We carried out a cross-sectional study of people with type 2 diabetes mellitus to elucidate the association between sleep duration and food intake. MATERIALS AND METHODS: Overall, 2,887 participants with type 2 diabetes mellitus (mean age 63.0 years; 61.1% men; mean glycated hemoglobin level 7.5%) were included in this study. The participants' self-reported dietary habits and sleep duration were evaluated using a brief self-administered dietary history questionnaire and Pittsburgh Sleep Quality Index, respectively. The participants were categorized into the following four groups based on sleep duration: <6, 6-6.9, 7-7.9 (reference) and ≥8 h. RESULTS: No significant differences were observed between the groups regarding energy intake (kcal/day), absolute intake (g/day) or relative intake (% energy) of carbohydrates, total fat, proteins and fibers. However, confectionery intake was higher in the <6 h group and lower in the ≥8 h group than in the reference group after adjustment for confounding factors. In multivariate analysis, sleep durations <6 h and ≥8 h significantly correlated with increased (95% confidence interval 0.55 to 3.6; P = 0.0078) and decreased (95% confidence interval -4.0 to -0.32; P = 0.021) confectionery intake, respectively. Confectionery intake was positively correlated with female sex, glycated hemoglobin level and dyslipidemia, whereas it was negatively correlated with alcohol consumption and current smoking status. CONCLUSIONS: Short sleep duration is associated with high confectionery intake in people with type 2 diabetes mellitus; this might disturb their glycemic control. Therefore, short sleepers with type 2 diabetes mellitus could improve their glycemic control by avoiding confectionery intake and maintaining adequate sleep duration.

    DOI： 10.1111/jdi.13987

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  • The METRO study: a retrospective analysis of the efficacy of metformin for type 2 diabetes in Japan.

    Marina Harada, Yoshinobu Kondo, Mai Sugiyama, Akeo Ohira, Masahiro Ichikawa, Tomoaki Akiyama, Kazuki Orime, Takanori Takai, Tadashi Yamakawa, Yasuo Terauchi

    Endocrine journal   70 ( 1 )   121 - 128   2023年1月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Metformin monotherapy as first-line treatment for patients with type 2 diabetes (T2D) has been shown to effectively improve blood glucose levels and motivation to undergo treatment and prevent complications. However, no studies have reported its effect when combined with other drugs or compared the effect based on administration time. This study aimed to investigate the effect of metformin administration in Japanese patients with T2D, examine how the introduction line impacts the effect of metformin, and examine the characteristics of patients demonstrating improved blood glucose levels. Data on characteristics of patients who were newly prescribed metformin with no shifting of hypoglycemic agents in the subsequent 24-week observation period, and their age [mean, 56.8 years], body mass index [mean, 27.5 kg/m2], glycated hemoglobin [HbA1c] [mean, 8.1%], and duration of diabetes [mean, 3.0 years] were obtained from the medical records of 201 patients. The changes in HbA1c by introduction line after 24 weeks were -1.59%, -0.91%, -0.89%, and -0.65% in the first, second, third, and fourth induction lines, respectively; earlier introduction more significantly improved blood glucose. The factors significantly associated with HbA1c changes were early introduction, high baseline HbA1c, high estimated glomerular filtration rate, decreased insulin secretion, short estimated duration of diabetes, and increased metformin dose. Furthermore, factors contributing to the largest HbA1c improvement by metformin were high baseline HbA1c and early administration. Metformin is expected to lower blood glucose levels in Japanese patients with T2D, even in those with decreased insulin secretion, due to its early introduction as a first-line drug.

    DOI： 10.1507/endocrj.EJ22-0330

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  • Comparing the course and delivery outcomes of Japanese twin pregnancies with and without gestational diabetes mellitus: a single-center retrospective analysis.

    Mai Sugiyama, Tadashi Yamakawa, Marina Harada, Akeo Ohira, Masahiro Ichikawa, Tomoaki Akiyama, Kazuki Orime, Sayuri Nakanishi, Shigeru Aoki, Yasuo Terauchi

    Endocrine journal   69 ( 10 )   1183 - 1191   2022年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Singleton pregnant women with gestational diabetes mellitus (GDM) are at an increased risk of adverse maternal and neonatal outcomes. Multiple pregnancies are associated with increased risks of perinatal complications; however, the impact of GDM on maternal and neonatal outcomes in multiple pregnancies is unknown, and there are currently few reports on GDM status in twin pregnancies. This study aimed to compare the background and perinatal outcomes between Japanese twin pregnancies with and without GDM at a perinatal center in Japan. Additionally, the clinical course of GDM was investigated. In this retrospective cohort study, women with twin pregnancies underwent GDM screening at Yokohama City University Medical Center from January 2011 to December 2016. Overall, 307 twin pregnancies were divided into GDM (47 cases, 15.3%) and non-GDM (260 cases, 84.7%) groups. GDM-associated pregnancy complications, GDM status, and pregnancy outcomes were ascertained. Women with GDM were older and had a higher pre-pregnancy body mass index than those without GDM. Glycemic control was good in all patients, and there was no difference in delivery outcomes between the two groups. Gestational weight gain was lower in pregnant women with GDM (+8.0 kg) than in those without GDM (+11.8 kg), suggesting the impact of strict nutritional guidance on twin pregnancies with GDM. In conclusion, twin pregnancies with GDM did not have different delivery outcomes compared to those without GDM. To manage twin pregnancies with GDM, this study suggests that it is important to monitor patients' weight and blood glucose levels.

    DOI： 10.1507/endocrj.EJ21-0537

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  • Association of continuous positive airway pressure therapy on cardiac hypertrophy in patients with sleep apnea comorbid with type 2 diabetes mellitus.

    Akeo Ohira, Tadashi Yamakawa, Noriaki Iwahashi, Shunichi Tanaka, Mai Sugiyama, Marina Harada, Masahiro Ichikawa, Tomoaki Akiyama, Kazuki Orime, Yasuo Terauchi

    Endocrine journal   70 ( 1 )   47 - 58   2022年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Previous reports indicated the therapeutic effect of chronic continuous positive airway pressure (CPAP) therapy on cardiac hypertrophy due to sleep apnea syndrome. However, little is known for cases involving diabetic complications. This retrospective observational study examined the effects of CPAP therapy on left ventricular hypertrophy (LVH) in patients with obstructive sleep apnea syndrome (OSAS) and type 2 diabetes mellitus (T2DM). For all cases, the observation period was 3 years from the time when the patient was introduced to CPAP therapy. Overall, 123 patients were divided into a good CPAP group (CPAP ≥4 h/day, n = 63) and non-adherence group (CPAP <4 h/day, n = 60). The mean CPAP usage times were 5.58 ± 1.23 and 1.03 ± 1.17 h/day in the good CPAP and non-adherence groups, respectively. Regression tendencies of the thickness of the left ventricular posterior (-0.30 ± 1.19 mm) and interventricular septal walls (-0.48 ± 1.22 mm) were observed in the good CPAP group. Hypertrophic tendencies of the left ventricular posterior wall (+0.59 ± 1.44 mm) and interventricular septal wall thickness (+0.59 ± 1.43) were observed in the non-adherence group. Left ventricular posterior wall thickness (odds ratio, (coefficient: -0.254, p = 0.0376) and interventricular septal wall thickness (coefficient: -0.426, p = 0.0006) were more likely to be greater in the non-adherence group than in the good CPAP group. Patients in the non-adherence group with an apnea hypopnea index ≥30 had increased left ventricular posterior wall thickness (coefficient: -0.263, p = 0.0673) and interventricular septal wall thickness (coefficient: -0.450, p = 0.0011). In conclusion, appropriate CPAP therapy is an effective treatment for LVH in patients with T2DM and OSAS, especially for severe cases.

    DOI： 10.1507/endocrj.EJ22-0308

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  • 難治性低血糖を呈した転移性腎盂尿管癌合併高分子IGF-2産生腫瘍の一例

    赤松 遼一, 奥山 朋子, 白川 純, 都野 貴裕, 岡村 紗弥, 平松 裕貴, 中口 裕達, 京原 麻由, 富樫 優, 折目 和基, 寺内 康夫

    日本内分泌学会雑誌   98 ( 1 )   370 - 370   2022年4月

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    記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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  • Autosomal dominant diabetes associated with a novel ZYG11A mutation resulting in cell cycle arrest in beta-cells. 国際誌

    Chutima Charoensuk, Prapaporn Jungtrakoon Thamtarana, Chutima Chanprasert, Watip Tangjittipokin, Jun Shirakawa, Yu Togashi, Kazuki Orime, Pucharee Songprakhon, Chartchai Chaichana, Zuroida Abubakar, Paweena Ouying, Jatuporn Sujjitjoon, Alessandro Doria, Nattachet Plengvidhya, Pa-Thai Yenchitsomanus

    Molecular and cellular endocrinology   522   111126 - 111126   2020年12月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Diabetes is a genetically heterogeneous disease, for which we are aiming to identify causative genes. Here, we report a missense mutation (c.T1424C:p.L475P) in ZYG11A identified by exome sequencing as segregating with hyperglycemia in a Thai family with autosomal dominant diabetes. ZYG11A functions as a target recruitment subunit of an E3 ubiquitin ligase complex that plays an important role in the regulation of cell cycle. We demonstrate an increase in cells arrested at G2/mitotic phase among beta-cells deficient for ZYG11A or overexpressing L475P-ZYG11A, which is associated with a decreased growth rate. This is the first evidence linking a ZYG11A mutation to hyperglycemia, and suggesting ZYG11A as a cell cycle regulator required for beta-cell growth. Since most family members were either overweight or obese, but only mutation carriers developed hyperglycemia, our data also suggests the ZYG11A mutation as a genetic factor predisposing obese individuals to beta-cell failure in maintenance of glucose homeostasis.

    DOI： 10.1016/j.mce.2020.111126

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  • Efficacy and safety of saxagliptin for the treatment of type 2 diabetes mellitus. 査読 国際誌

    Kazuki Orime, Yasuo Terauchi

    Expert opinion on pharmacotherapy   1 - 14   2020年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    INTRODUCTION: Saxagliptin, a member of the dipeptidyl peptidase-4 inhibitor (DPP-4i) class of drugs, was approved by the FDA for the treatment of type 2 diabetes (T2D) in 2009, and has been in clinical use for more than a decade. Since the drug was first launched, much real-world evidence has also been accumulated. The efficacy and safety of saxagliptin, especially its cardiovascular safety, are of particular interest. AREAS COVERED: This review provides an overview of the safety and efficacy of saxagliptin based on observational studies, pharmacovigilance, and meta-analyses. In addition, with the findings of recent cardiovascular outcome trials (CVOTs), the authors discuss, herein, the efficacious use of saxagliptin. EXPERT OPINION: Saxagliptin exhibits a moderate glucose-lowering effect and is well tolerated by patients with T2D. SAVOR-TIMI 53, a CVOT of saxagliptin, reported neutral effects of saxagliptin in respect of the cardiovascular outcomes, but did raise a concern about the risk of heart failure. Conversely, recent CVOTs on sodium-glucose co-transporter-2 inhibitors (SGLT2i) have shown a favorably reduced risk of heart failure with these drugs. Also, DPP-4is decrease the serum glucagon level, whereas the SGLT2is increase it. Given the characteristics of the two classes of drugs, combined therapy with the two might be a promising option.

    DOI： 10.1080/14656566.2020.1803280

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  • Parental metabolic syndrome epigenetically reprograms offspring hepatic lipid metabolism in mice. 査読

    De Jesus DF, Orime K, Kaminska D, Kimura T, Basile G, Wang CH, Haertle L, Riemens R, Brown NK, Hu J, Männistö V, Silva AM, Dirice E, Tseng YH, Haaf T, Pihlajamäki J, Kulkarni RN

    J Clin Invest   2020年4月

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  • Improved home BP profile with dapagliflozin is associated with amelioration of albuminuria in Japanese patients with diabetic nephropathy: the Yokohama add-on inhibitory efficacy of dapagliflozin on albuminuria in Japanese patients with type 2 diabetes study (Y-AIDA study). 査読 国際誌

    Sho Kinguchi, Hiromichi Wakui, Yuzuru Ito, Yoshinobu Kondo, Kengo Azushima, Uru Osada, Tadashi Yamakawa, Tamio Iwamoto, Jun Yutoh, Toshihiro Misumi, Kazutaka Aoki, Gen Yasuda, Taishi Yoshii, Takayuki Yamada, Syuji Ono, Tomoko Shibasaki-Kurita, Saho Hosokawa, Kazuki Orime, Masaaki Hanaoka, Hiroto Sasaki, Kohji Inazumi, Taku Yamada, Ryu Kobayashi, Kohji Ohki, Kotaro Haruhara, Yusuke Kobayashi, Takeharu Yamanaka, Yasuo Terauchi, Kouichi Tamura

    Cardiovascular diabetology   18 ( 1 )   110 - 110   2019年8月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    BACKGROUND: The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria. METHODS: We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0-10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24. RESULTS: Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 (P < 0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP - 8.32 ± 11.42/- 4.18 ± 5.91 mmHg (both P < 0.001), evening systolic/diastolic BP - 9.57 ± 12.08/- 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP - 2.38 ± 7.82/- 1.17 ± 5.39 mmHg (P = 0.0079 for systolic BP, P = 0.0415 for diastolic BP). Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR. CONCLUSIONS: In Japanese patients with T2DM and diabetic nephropathy, dapagliflozin significantly improved albuminuria levels and the home BP profile. Improved morning home systolic BP was associated with albuminuria reduction. Trial registration The study is registered at the UMIN Clinical Trials Registry (UMIN000018930; http://www.umin.ac.jp/ctr/index-j.htm ). The study was conducted from July 1, 2015 to August 1, 2018.

    DOI： 10.1186/s12933-019-0912-3

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  • 遷延する低血糖脳症から回復した認知症合併高齢2型糖尿病患者の1例

    國下 梨枝子, 富樫 優, 折目 和基, 高嶺 光, 中口 裕達, 細川 紗帆, 田島 一樹, 伊藤 譲, 寺内 康夫

    糖尿病   61 ( 9 )   648 - 648   2018年9月

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    記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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  • 血糖コントロール増悪を契機に発見された巨大副腎腫瘍の1例

    中口 裕達, 國下 梨枝子, 高嶺 光, 細川 紗帆, 折目 和基, 寺内 康夫

    糖尿病   61 ( 8 )   568 - 568   2018年8月

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    記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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  • Signaling between pancreatic β cells and macrophages via S100 calcium-binding protein A8 exacerbates β-cell apoptosis and islet inflammation. 査読 国際誌

    Inoue H, Shirakawa J, Togashi Y, Tajima K, Okuyama T, Kyohara M, Tanaka Y, Orime K, Saisho Y, Yamada T, Shibue K, Kulkarni RN, Terauchi Y

    J Biol Chem   293 ( 16 )   5934 - 5946   2018年4月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1074/jbc.M117.809228

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  • 2型糖尿病患者におけるSGLT2阻害薬の糖尿病性腎症関連バイオマーカー変化に及ぼす影響の検討

    小西 裕美, 白川 純, 田島 一樹, 細川 紗帆, 國下 梨枝子, 中口 裕達, 奥山 朋子, 折目 和基, 富樫 優, 伊藤 譲, 寺内 康夫

    糖尿病   59 ( Suppl.1 )   S - 231   2016年4月

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    記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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  • Lipid-lowering agents inhibit hepatic steatosis in a non-alcoholic steatohepatitis-derived hepatocellular carcinoma mouse model. 査読 国際誌

    Kazuki Orime, Jun Shirakawa, Yu Togashi, Kazuki Tajima, Hideaki Inoue, Yoji Nagashima, Yasuo Terauchi

    European journal of pharmacology   772 ( 772 )   22 - 32   2016年2月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Non-alcoholic fatty liver disease (NAFLD) is associated with various metabolic disorders, and the therapeutic strategies for treating NAFLD and non-alcoholic steatohepatitis (NASH) have not been fully established. In the present study, we examined whether lipid-lowering agents inhibited the progression of NAFLD and tumorigenesis in a non-alcoholic steatohepatitis-derived hepatocellular carcinoma model mouse (STAM mice) generated by streptozotocin injection and a high-fat diet. Seven-week-old STAM mice were divided into groups fed a high-fat diet (Ctl) or a high-fat diet supplemented with ezetimibe (Ez), fenofibrate (Ff), rosuvastatin (Rs), ezetimibe plus fenofibrate (EF), or ezetimibe plus rosuvastatin (ER) for 4 weeks. At the end of the experiments, an oral glucose tolerance test, an insulin tolerance test, biochemical analyses using serum and liver, and a histological analysis of liver were performed in 11-week-old STAM mice. The lipid-lowering agents did not affect the body weight or the casual blood glucose levels in any of the groups. The serum triglyceride level was significantly decreased by Ff, Rs, and EF. Glucose tolerance was improved by Ez and Ff, but none of these agents improved insulin sensitivity. A histochemical analysis revealed that the lipid-lowering agents, with the exception of Rs, significantly inhibited the progression of hepatic steatosis. Nonetheless, no significant changes in the incidence of hepatic tumors were observed in any of the groups. Lipid-lowering agents inhibited the progression of hepatic steatosis without suppressing tumorigenesis in STAM mice. Our data has implications for the mechanism underlying steatosis-independent hepatic tumorigenesis in mice.

    DOI： 10.1016/j.ejphar.2015.12.043

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  • インスリノーマとガストリノーマの合併が疑われたMEN1型の1例

    伊藤 浩平, 田島 一樹, 國下 梨枝子, 町村 哲郎, 中口 裕達, 細川 紗帆, 折目 和基, 富樫 優, 伊藤 譲, 寺内 康夫

    日本内分泌学会雑誌   91 ( 3 )   833 - 833   2015年10月

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    記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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  • β-Cell proliferation after a partial pancreatectomy is independent of IRS-2 in mice. 査読 国際誌

    Endocrinology   155 ( 5 )   1643 - 52   2014年5月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1210/en.2013-1796

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  • Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 mice 査読

    K. Tajima, A. Nakamura, J. Shirakawa, Y. Togashi, K. Orime, K. Sato, H. Inoue, M. Kaji, E. Sakamoto, Y. Ito, K. Aoki, Y. Nagashima, T. Atsumi, Y. Terauchi

    AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM   305 ( 8 )   E987 - E998   2013年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PHYSIOLOGICAL SOC  

    The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing with the growing epidemics of obesity and diabetes. NAFLD encompasses a clinicopathologic spectrum of disease ranging from isolated hepatic steatosis to NASH, which is a more aggressive form of fatty liver disease, to cirrhosis and, finally, hepatocellular carcinoma (HCC). The exact mechanism behind the development of HCC in NASH remains unclear; however, it has been established that hepatic steatosis is the important risk factor in the development of HCC. Metformin has recently drawn attention because of its potential antitumor effect. Here, we investigated the effects of metformin on high-fat diet (HFD)-induced liver tumorigenesis, using a mouse model of NASH and liver tumor. Metformin prevented long-term HFD-induced liver tumorigenesis in C57Bl/6 mice. Of note, metformin failed to protect against liver tumorigenesis in mice that had already begun to develop NAFLD. Metformin improved short-term HFD-induced fat accumulation in the liver, associated with the suppression of adipose tissue inflammation. Collectively, these results suggest that metformin may prevent liver tumorigenesis via suppression of liver fat accumulation in the early stage, before the onset of NAFLD, which seems to be associated with a delay in the development of inflammation of the adipose tissue.

    DOI： 10.1152/ajpendo.00133.2013

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  • Glucokinase activation ameliorates ER stress-induced apoptosis in pancreatic β-cells. 査読 国際誌

    Shirakawa J, Togashi Y, Sakamoto E, Kaji M, Tajima K, Orime K, Inoue H, Kubota N, Kadowaki T, Terauchi Y

    Diabetes   62 ( 10 )   3448 - 58   2013年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.2337/db13-0052

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  • Trefoil factor 2 promotes cell proliferation in pancreatic β-cells through CXCR-4-mediated ERK1/2 phosphorylation. 査読 国際誌

    Orime K, Shirakawa J, Togashi Y, Tajima K, Inoue H, Ito Y, Sato K, Nakamura A, Aoki K, Goshima Y, Terauchi Y

    Endocrinology   154 ( 1 )   54 - 64   2013年1月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1210/en.2012-1814

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  • AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration. 査読 国際誌

    Kazuki Tajima, Jun Shirakawa, Yu Togashi, Hideaki Inoue, Koichiro Sato, Kazuki Orime, Yuzuru Ito, Mitsuyo Kaji, Eri Sakamoto, Akinobu Nakamura, Kazutaka Aoki, Yoshio Goshima, Tatsuya Atsumi, Yasuo Terauchi

    PloS one   8 ( 5 )   e64633   2013年

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    The precise role of AMP-activated protein kinase (AMPK), a target of metformin, in pancreatic β cells remains controversial, even though metformin was recently shown to enhance the expression of incretin receptors (GLP-1 and GIP receptors) in pancreatic β cells. In this study, we investigated the effect of AMPK in the regulation of incretin receptors expression in pancreatic islets. The phosphorylation of AMPK in the mouse islets was decreased by increasing glucose concentrations. We showed the expression of incretin receptors in bell-shaped response to glucose. Expression of the incretin receptors in the isolated islets showed higher levels under a medium glucose concentration (11.1 mM) than that under a low glucose concentration (2.8 mM), but was suppressed under a high glucose concentration (22.2 mM). Both treatment with an AMPK inhibitor and DN-AMPK expression produced a significant increase of the incretin receptors expression under a low glucose concentration. By contrast, in hyperglycemic db/db islets, the enhancing effect of the AMPK inhibitor on the expression of incretin receptors was diminished under a low glucose concentration. Taken together, AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration.

    DOI： 10.1371/journal.pone.0064633

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  • Plasminogen activator inhibitor-1 is associated with renal dysfunction independent of BMI and serum lipid levels in patients with type 2 diabetes. 査読 国際誌

    Jun Shirakawa, Yu Togashi, Kazuki Tajima, Kazuki Orime, Kaori Kikuchi, Takashi Miyazaki, Koichiro Sato, Mari Kimura, Yoshio Goshima, Yasuo Terauchi

    Diabetes research and clinical practice   97 ( 1 )   e9-12 - e12   2012年7月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    We investigated a possible association between serum plasminogen activator inhibitor-1 (PAI-1) levels and renal dysfunction in 124 type 2 diabetes patients. Multiple linear regression analyses indicated that the PAI-1 levels were significantly inversely correlated with estimated glomerular filtration rate (eGFR) independent of albuminuria, BMI, LDL-C, and triglyceride.

    DOI： 10.1016/j.diabres.2012.03.017

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  • Effects of liraglutide on β-cell-specific glucokinase-deficient neonatal mice. Endocrinology. 査読 国際誌

    Shirakawa J, Tanami R, Togashi Y, Tajima K, Orime K, Kubota N, Kadowaki T, Goshima Y, Terauchi Y

    153 ( 7 )   3066 - 75   2012年7月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1210/en.2012-1165

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  • Control of beta cell function and proliferation in mice stimulated by small-molecule glucokinase activator under various conditions 査読

    A. Nakamura, Y. Togashi, K. Orime, K. Sato, J. Shirakawa, M. Ohsugi, N. Kubota, T. Kadowaki, Y. Terauchi

    DIABETOLOGIA   55 ( 6 )   1745 - 1754   2012年6月

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

    We investigated changes in the expression of genes involved in beta cell function and proliferation in mouse islets stimulated with glucokinase activator (GKA) in order to elucidate the mechanisms by which GKA stimulates beta cell function and proliferation.
    Islets isolated from mice were used to investigate changes in the expression of genes related to beta cell function and proliferation stimulated by GKA. In addition, knockout ( (-/-)) mice on a high-fat diet or a high-fat diet containing GKA were used to investigate the effects of GKA on beta cell proliferation in vivo.
    In wild-type mice, and expression was increased by GKA. In (-/-) mice, GKA administration increased the glucose-stimulated secretion of insulin and expression, but not beta cell proliferation. It was particularly noteworthy that oxidative stress inhibited the upregulation of the and genes induced by GKA. Moreover, whereas neither GKA alone nor exendin-4 alone upregulated the expression of and in the islets of / mice, prior administration of exendin-4 to the mice caused GKA to increase the expression of these genes.
    GKA-stimulated IRS2 production affected beta cell proliferation but not beta cell function. Oxidative stress diminished the effects of GKA on the changes in expression of genes involved in beta cell function and proliferation. A combination of GKA and an incretin-related agent might therefore be effective in therapy.

    DOI： 10.1007/s00125-012-2521-5

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  • Impact of the dipeptidyl peptidase-4 inhibitor vildagliptin on glucose tolerance and β-cell function and mass in insulin receptor substrate-2-knockout mice fed a high-fat diet. 査読 国際誌

    Sato K, Nakamura A, Shirakawa J, Muraoka T, Togashi Y, Shinoda K, Orime K, Kubota N, Kadowaki T, Terauchi Y

    Endocrinology   153 ( 3 )   1093 - 102   2012年3月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1210/en.2011-1712

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  • Double-blind randomized clinical trial of the effects of ezetimibe on postprandial hyperlipidaemia and hyperglycaemia. 査読

    Kaori Kikuchi, Uru Nezu, Koji Inazumi, Takashi Miyazaki, Kanako Ono, Kazuki Orime, Jun Shirakawa, Koichiro Sato, Hirofumi Koike, Tadashi Wakasugi, Misako Sato, Chihiro Kawakami, Shinichiro Watanabe, Tadashi Yamakawa, Yasuo Terauchi

    Journal of atherosclerosis and thrombosis   19 ( 12 )   1093 - 101   2012年

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    AIM: Ezetimibe selectively blocks intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1 (NPC1L1) and reducing LDL cholesterol (LDL-C). In animals, ezetimibe reversed diet-induced obesity, liver steatosis, and insulin resistance. In humans, its potential effects on liver steatosis and insulin resistance have been suggested. We investigated the effects of ezetimibe on postprandial hyperlipidaemia and hyperglycaemia in obese subjects with dyslipidaemia in a double-blind randomized crossover trial. METHODS: Twenty obese men with hypertriglyceridaemia were assigned randomly to an ezetimibe- or a placebo-precedence-treated group. Subjects in the ezetimibe group were treated with ezetimibe (10 mg/day) for the first 4 weeks, followed by a 4-week interval and then treated with placebo for another 4 weeks. The placebo group received these treatments in reverse order. Subjects were requested to fast for at least 12 hours and then received a standard meal. Blood samples were collected at 0, 30, 60, 120, 240, 360 and 480 minutes after the meal on Days 0, 28, 56 and 84 and were used to measure the lipid and glucose metabolism markers. RESULTS: Ezetimibe significantly decreased the postprandial serum triglyceride excursion (p=0.01) and fasting serum LDL-C, remnant-like particles(RLP) and ApoB48 levels (p<0.05). Postprandial glucose excursion, serum insulin levels, serum glucose-dependent insulinotropic polypeptide (GIP) and active glucagon-like peptide-1 (GLP-1) were not significantly affected by ezetimibe treatment. CONCLUSION: Ezetimibe restored the postprandial dysregulation of lipid but did not affect glucose metabolism in a double-blind randomized crossover trial.

    DOI： 10.5551/jat.12427

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  • Protective effects of dipeptidyl peptidase-4 (DPP-4) inhibitor against increased β cell apoptosis induced by dietary sucrose and linoleic acid in mice with diabetes. 査読 国際誌

    Shirakawa J, Amo K, Ohminami H, Orime K, Togashi Y, Ito Y, Tajima K, Koganei M, Sasaki H, Takeda E, Terauchi Y

    J Biol Chem   286 ( 29 )   25467 - 76   2011年7月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1074/jbc.M110.217216

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  • Effects of pre-meal versus post-meal administration of miglitol on plasma glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide levels in healthy men 査読

    Kazutaka Aoki, Takashi Miyazaki, Jo Nagakura, Kazuki Orime, Yu Togashi, Yasuo Terauchi

    ENDOCRINE JOURNAL   57 ( 8 )   673 - 677   2010年8月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN ENDOCRINE SOC  

    We previously reported that the administration a miglitol after a meal was equally effective as administration before a meal Since glucaizon-like peptide-1 (GLP-1) reportedly promotes islet cell growth and inhibits apoptosis in animal models, an increase in GLP-1 secretion might also be beneficial for islet cell function and mass in humans Miglitol reportedly enhances GLP-1 responses and reduces glucose-dependent insulinotropic polypeptide (GIP) However, whether the effect of miglitol on these incretins is comparable when mightol is administered before or arm a meal remains uncertain Here, we compared the effects of the pre-meal versus post-meal administration of miglitol on the plasma active GLP-1 and total GIP levels in healthy men Mightol was administered according to three different intake schedules in each subject (control no drug, intake I drug administered just before a meal 150 mg], intake 2 drug administered at 30 min after the start of a meal [50 mg]) The area under the curve (AUC) of the plasma GLP-1 level for the intake 1 group was significantly greater than those of the control and intake 2 groups The AUCs of the plasma GIP level for the intake 1 and 2 groups were significantly smaller than that of the control The administration of miglitol just before a meal, rather than after a meal, is recommended in view of the up-regulation of GLP-1

    DOI： 10.1507/endocrj.K10E-064

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書籍等出版物

  • 臨床雑誌『内科』最新の糖尿病診療と今後の展開

    折目和基（ 担当： 共著 範囲: 最新の糖尿病診療総論）

    2022年5月 

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  • 糖尿病グリーンノート

    折目和基（ 担当： 共著 範囲: 1診療録（カルテ） 2退院サマリー 3処方箋 4入院時診療計画書）

    2016年10月 

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  • 糖尿病診療マスター

    折目 和基（ 担当： 分担執筆 範囲: グルコキナーゼ活性化薬）

    医学書院  2015年12月 

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  • CORE Journal循環器

    折目 和基（ 担当： 分担執筆 範囲: インスリン）

    ライフサイエンス出版  2013年6月 

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  • 糖尿病の分子標的と治療薬事典

    折目 和基（ 担当： 分担執筆 範囲: インスリン作用促進薬）

    羊土社  2013年5月 

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  • 動脈硬化予防 prevention of arteriosclerosis

    折目 和基（ 担当： 分担執筆 範囲: 内外のガイドラインにみる血糖管理と動脈硬化予防）

    メジカルレビュー社  2012年1月 

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  • 臨床検査値express

    折目 和基（ 担当： 分担執筆 範囲: L-Dopa負荷試験）

    神陵文庫  2011年 

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  • 高血圧NAVIGATOR（第3版）

    折目 和基（ 担当： 分担執筆 範囲: PPARγ）

    メディカルレビュー社  2011年 

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  • 日本臨床 増刊 メタボリックシンドローム（第2版）

    折目 和基（ 担当： 分担執筆 範囲: インスリン受容体以降のインスリン情報伝達経路の異常）

    日本臨床社  2011年 

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  • 日本臨床 増刊 広範囲 血液・尿化学検査 免疫学的検査(第7版・4)

    折目 和基（ 担当： 分担執筆 範囲: インスリン受容体基質 (IRS)）

    日本臨床社  2010年 

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  • 日本臨床 増刊 肥満症（第2版）－基礎・臨床研究の進歩－

    折目 和基（ 担当： 分担執筆 範囲: PPARγ遺伝子異常）

    日本臨床社  2010年 

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  • EBM糖尿病ハンドブック

    折目 和基（ 担当： 分担執筆 範囲: 2型糖尿病）

    中外医学社  2010年 

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MISC

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共同研究・競争的資金等の研究課題

  • プロテアーゼインヒビターによるインスリン分泌制御とインスリン抵抗性形成機構の解明

    研究課題/領域番号：20K17540  2020年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    折目 和基

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    配分額：4160000円 （ 直接経費：3200000円 、 間接経費：960000円 ）

    糖尿病を発症する重要な因子として、インスリン分泌の低下やインスリン抵抗性が挙げられる。我々はこれまでにインスリン抵抗性状態下での代償性膵β細胞増殖に寄与する肝細胞由来の液性因子としてSerpinB1を報告している。本研究では、肝細胞におけるSerpinB1の発現調節メカニズムと機能について検討した。まず、肝臓でのSerpinB1の発現は、サイトカインであるインターロイキン-6（IL-6）が、JAK / STAT3経路を介して制御していることを明らかにした。また、肝細胞内でのSerpinB1はインスリンシグナルの伝達に重要であるインスリン受容体の発現制御に関与していることも明らかにした。

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  • 膵β細胞増殖促進因子SerpinB1の発現制御による新たな糖尿病治療法の探索

    研究課題/領域番号：19K23949  2019年8月 - 2021年3月

    日本学術振興会  科学研究費助成事業 研究活動スタート支援  研究活動スタート支援

    折目 和基

    　 詳細を見る

    配分額：2860000円 （ 直接経費：2200000円 、 間接経費：660000円 ）

    糖尿病発症の要因としてインスリン抵抗性とインスリン分泌低下が重要である。我々は代償性膵β細胞増殖に寄与する肝細胞由来の液性因子としてSerpinB1を報告しており、本研究では肝細胞におけるSerpinB1の発現調節メカニズムについて検討した。肝臓のSerpinB1の発現は、高度のインスリン抵抗性を示すdb/dbおよびob/obマウスで上昇しており、これらの血清で高値を示すインターロイキン-6(IL-6)は、JAK/STAT3経路を介してSerpinB1の発現を上昇させたことから、インスリン抵抗性下の代償性膵β細胞増殖にIL-6/JAK/STAT3経路が重要であることが示唆された。

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