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大学院医学系研究科（医学専攻等） 医学専攻 病態制御医学系 代謝・内分泌内科学講座 |
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研究室住所 |
秋田市本道一丁目1の1 |
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研究室電話 |
018-884-6769 |
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メールアドレス |
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脇 裕典 (ワキ ヒロノリ)
WAKI Hironori
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職務経歴（学外） 【 表示 ／ 非表示 】
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2019年09月-2021年05月
東京大学大学院医学系研究科代謝・栄養病態学 准教授
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2018年11月-2019年08月
東京大学大学院医学系研究科代謝・栄養病態学 講師
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2016年09月-2018年10月
東京大学大学院医学系研究科分子糖尿病科学 特任准教授
研究分野 【 表示 ／ 非表示 】
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ライフサイエンス / 分子生物学 / Molecular biology
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ライフサイエンス / 栄養学、健康科学
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ライフサイエンス / 細胞生物学 / Cellular biology
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ライフサイエンス / 遺伝学 / Genomics
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ライフサイエンス / 代謝、内分泌学 / Diabetes and Metabolic Diseases
研究等業績 【 表示 ／ 非表示 】
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Recurrent nocturnal hypoglycemic hemiplegia: a case report and review of the literature.
Hanako Toyama, Kazuyuki Takahashi, Tatsunori Shimizu, Izumi Otaka, Sakiko Abe, Shunsuke Kato, Sayaka Ando, Takehiro Sato, Tsukasa Morii, Hiroki Fujita, Hironori Waki
Endocrine journal 2024年02月 [査読有り]
研究論文（学術雑誌）
A 67-year-old man with type 1 diabetes, Cronkhite-Canada syndrome, and membranous nephropathy who received insulin therapy was admitted to our hospital with right hemiplegia and dysarthria. Brain magnetic resonance imaging revealed a lesion with a high diffusion-weighted imaging signal and low apparent diffusion coefficient signal in the posterior limb of the left internal capsule. He was hypoglycemic with a blood glucose level of 56 mg/dL (3.1 mmol/L). Following glucose administration, the patient's symptoms resolved within several hours. The patient experienced similar transient hypoglycemic hemiplegia at midnight, three times within 10 days. In a literature review of 170 cases of hypoglycemic hemiplegia, 26 cases of recurrent hemiplegia were investigated. Recurrent hypoglycemic hemiplegia occurs more frequently on the right side than on the left side, and most recurrences occur within approximately a week, almost exclusively at midnight and in the early morning. We speculate that hypoglycemia-associated autonomic failure may be involved in the nocturnal recurrence of episodes. In our patient, depleted endogenous insulin secretion and lipodystrophy at the injection site, may have acted as additional factors, leading to severe hypoglycemia despite the absence of apparent autonomic neuropathy. Clinically, it is important to recognize hypoglycemia as a cause of hemiplegia to avoid unnecessary intervention and to maintain an appropriate blood glucose level at midnight and early in the morning to prevent recurrent hypoglycemic hemiplegia.
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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.
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02月
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.
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Gastric inhibitory polypeptide receptor antagonism suppresses intramuscular adipose tissue accumulation and ameliorates sarcopenia.
Yuya Takahashi, Hiroki Fujita, Yusuke Seino, Satoko Hattori, Shihomi Hidaka, Tsuyoshi Miyakawa, Atsushi Suzuki, Hironori Waki, Daisuke Yabe, Yutaka Seino, Yuichiro Yamada
Journal of cachexia, sarcopenia and muscle 2023年10月
研究論文（学術雑誌）
BACKGROUND: Intramuscular adipose tissue (IMAT) formation derived from muscle fibro-adipogenic progenitors (FAPs) has been recognized as a pathological feature of sarcopenia. This study aimed to explore whether genetic and pharmacological gastric inhibitory polypeptide (GIP) receptor antagonism suppresses IMAT accumulation and ameliorates sarcopenia in mice. METHODS: Whole body composition, grip strength, skeletal muscle weight, tibialis anterior (TA) muscle fibre cross-sectional area (CSA) and TA muscle IMAT area were measured in young and aged male C57BL/6 strain GIP receptor (Gipr)-knockout (Gipr-/- ) and wild-type (Gipr+/+ ) mice. FAPs isolated from lower limb muscles of 12-week-old Gipr+/+ mice were cultured with GIP, and their differentiation into mature adipocytes was examined. Furthermore, TA muscle IMAT area and fibre CSA were measured in untreated Gipr-/- mice and GIP receptor antagonist-treated Gipr+/+ mice after glycerol injection into the TA muscles. RESULTS: Body composition analysis revealed that 104-week-old Gipr-/- mice had a greater proportion of lean tissue mass (73.7 ± 1.2% vs. 66.5 ± 2.7%, P < 0.05 vs. 104-week-old Gipr+/+ mice) and less adipose tissue mass (13.1 ± 1.3% vs. 19.4 ± 2.6%, P < 0.05 vs. 104-week-old Gipr+/+ mice). Eighty-four-week-old Gipr-/- mice exhibited increases in grip strength (P < 0.05), weights of TA (P < 0.05), soleus (P < 0.01), gastrocnemius (P < 0.05) and quadriceps femoris (P < 0.01) muscles, and average TA muscle fibre CSA (P < 0.05) along with a reduction in TA muscle IMAT area assessed by the number of perilipin-positive cells (P < 0.0001) compared with 84-week-old Gipr+/+ mice. Oil Red O staining analysis revealed 1.6- and 1.7-fold increased adipogenesis in muscle FAPs cultured with 10 and 100 nM of GIP (P < 0.01 and P < 0.001 vs. 0 nM of GIP, respectively). Furthermore, both untreated Gipr-/- mice and GIP receptor antagonist-treated Gipr+/+ mice for 14 days after glycerol injection into the TA muscles at 12 weeks of age showed reduced TA muscle IMAT area (1.39 ± 0.38% and 2.65 ± 0.36% vs. 6.54 ± 1.30%, P < 0.001 and P < 0.01 vs. untreated Gipr+/+ mice, respectively) and increased average TA muscle fibre CSA (P < 0.01 and P < 0.05 vs. untreated Gipr+/+ mice, respectively). CONCLUSIONS: GIP promotes the differentiation of muscle FAPs into adipocytes and its receptor antagonism suppresses IMAT accumulation and promotes muscle regeneration. Pharmacological GIP receptor antagonism may serve as a novel therapeutic approach for sarcopenia.
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NFIA in adipocytes reciprocally regulates mitochondrial and inflammatory gene program to improve glucose homeostasis.
Yuta Hiraike, Kaede Saito, Misato Oguchi, Takahito Wada, Gotaro Toda, Shuichi Tsutsumi, Kana Bando, Junji Sagawa, Gaku Nagano, Haruya Ohno, Naoto Kubota, Tetsuya Kubota, Hiroyuki Aburatani, Takashi Kadowaki, Hironori Waki, Shintaro Yanagimoto, Toshimasa Yamauchi
Proceedings of the National Academy of Sciences of the United States of America 120 ( 31 ) e2308750120 2023年08月
研究論文（学術雑誌）
Adipose tissue is central to regulation of energy homeostasis. Adaptive thermogenesis, which relies on mitochondrial oxidative phosphorylation (Ox-Phos), dissipates energy to counteract obesity. On the other hand, chronic inflammation in adipose tissue is linked to type 2 diabetes and obesity. Here, we show that nuclear factor I-A (NFIA), a transcriptional regulator of brown and beige adipocytes, improves glucose homeostasis by upregulation of Ox-Phos and reciprocal downregulation of inflammation. Mice with transgenic expression of NFIA in adipocytes exhibited improved glucose tolerance and limited weight gain. NFIA up-regulates Ox-Phos and brown-fat-specific genes by enhancer activation that involves facilitated genomic binding of PPARγ. In contrast, NFIA in adipocytes, but not in macrophages, down-regulates proinflammatory cytokine genes to ameliorate adipose tissue inflammation. NFIA binds to regulatory region of the Ccl2 gene, which encodes proinflammatory cytokine MCP-1 (monocyte chemoattractant protein-1), to down-regulate its transcription. CCL2 expression was negatively correlated with NFIA expression in human adipose tissue. These results reveal the beneficial effect of NFIA on glucose and body weight homeostasis and also highlight previously unappreciated role of NFIA in suppressing adipose tissue inflammation.
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Relationships among Postprandial Plasma Active GLP-1 and GIP Excursions, Skeletal Muscle Mass, and Body Fat Mass in Patients with Type 2 Diabetes Treated with Either Miglitol, Sitagliptin, or Their Combination: A Secondary Analysis of the MASTER Study.
Masahiro Sato, Hiroki Fujita, Hiroki Yokoyama, Atsushi Mikada, Yohei Horikawa, Yuya Takahashi, Yuichiro Yamada, Hironori Waki, Takuma Narita
Journal of clinical medicine 12 ( 9 ) 2023年04月
研究論文（学術雑誌）
BACKGROUND: We previously conducted a pilot randomized controlled trial "the MASTER study" and demonstrated that alpha-glucosidase inhibitor miglitol and a dipeptidyl peptidase-4 inhibitor sitagliptin modified postprandial plasma excursions of active glucagon-like peptide-1 (aGLP-1) and active gastric inhibitory polypeptide (aGIP), and miglitol treatment decreased body fat mass in patients with type 2 diabetes (T2D). However, the details regarding the relationships among postprandial plasma aGLP-1 and aGIP excursions, skeletal muscle mass, and body fat mass are unclear. METHODS: We conducted a secondary analysis of the relationships among skeletal muscle mass index (SMI), total body fat mass index (TBFMI), and the incremental area under the curves (iAUC) of plasma aGLP-1 and aGIP excursions following mixed meal ingestion at baseline and after 24-week add-on treatment with either miglitol alone, sitagliptin alone, or their combination in T2D patients. RESULTS: SMI was not changed after the 24-week treatment with miglitol and/or sitagliptin. TBFMI was reduced and the rates of aGIP-iAUC change were lowered in the two groups treated with miglitol, although their correlations did not reach statistical significance. We observed a positive correlation between the rates of aGIP-iAUC and TBFMI changes and a negative correlation between the rates of TBFMI and SMI changes in T2D patients treated with sitagliptin alone whose rates of aGIP-iAUC change were elevated. CONCLUSIONS: Collectively, although T2D patients treated with miglitol and/or sitagliptin did not show altered SMI after 24-week treatment, the current study suggests that there are possible interrelationships among postprandial plasma aGIP excursion modified by sitagliptin, skeletal muscle mass, and body fat mass.
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脂肪細胞の最新科学
脇 裕典
Medical View Point ( 医事出版社 ) 44 ( 9 ) 6 - 6 2023年09月
総説・解説（商業誌）
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安藤清香, 脇裕典
診断と治療 ( (株)診断と治療社 ) 110 ( 10 ) 1281 - 1285 2022年10月
総説・解説（学術雑誌）
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高血糖と肥満の深い関係ー血糖値がなかなか下がらないときは過体重への対応が必要？
脇 裕典
月間糖尿病ライフ さかえ ( 日本糖尿病協会 ) 62 ( 9 ) 12 - 13 2022年09月
総説・解説（学術雑誌）
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田丸 新一, 諏訪内 浩紹, 小田原 雅人, 鈴木 亮, 脇 裕典, 山内 敏正
東京医科大学雑誌 ( 東京医科大学医学会 ) 80 ( 2 ) 158 - 158 2022年04月
研究論文（大学，研究機関紀要）
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GIPは筋線維間脂肪の形成を促進させて,サルコペニアの発症・進展に関与する
高橋 侑也, 藤田 浩樹, 脇 裕典, 山田 祐一郎
糖尿病合併症 ( (一社)日本糖尿病合併症学会 ) 37 ( Suppl.1 ) 131 - 131 2023年09月
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血管・動脈硬化・高血圧(1) インクレチン関連薬の有無で糖尿病合併高血圧症にSacubitril/valsartan(Sac/Val)投与120例への血糖コントロールの影響の検討
松田 大輔, 岩村 庄吾, 本郷 真伊, 小松 輝久, 田近 武伸, 奈良 藍子, 大高 いずみ, 阿部 咲子, 佐々木 可奈, 大友 瞳, 高橋 和之, 加藤 俊祐, 脇 裕典
糖尿病合併症 ( (一社)日本糖尿病合併症学会 ) 37 ( Suppl.1 ) 142 - 142 2023年09月
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Oral semaglutide225例で肝繊維化マーカーFIB-4 indexへの影響の検討
松田 大輔, 菅沼 由美, 本郷 真伊, 田近 武伸, 奈良 藍子, 大高 いずみ, 阿部 咲子, 佐々木 可奈, 大友 瞳, 高橋 和之, 加藤 俊祐, 山田 芙久子, 脇 裕典
日本内分泌学会雑誌 ( (一社)日本内分泌学会 ) 99 ( 1 ) 328 - 328 2023年05月
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GIPシグナルと骨格筋間葉系前駆細胞に着目したサルコペニアの病態解明
高橋 侑也, 藤田 浩樹, 脇 裕典, 山田 祐一郎
糖尿病 ( (一社)日本糖尿病学会 ) 66 ( Suppl.1 ) S - 145 2023年04月
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医科診療報酬「糖尿病透析予防指導管理科」算定開始の政策効果の推定
小林 真央, 森井 宰, 佐藤 雄大, 藤田 浩樹, 脇 裕典, 安藤 秀明
糖尿病 ( (一社)日本糖尿病学会 ) 66 ( Suppl.1 ) S - 151 2023年04月
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◆総説・解説【 表示 ／ 非表示 】
◆⼤学，研究機関紀要【 表示 ／ 非表示 】
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糖尿病学2023
脇裕典, 平池勇雄, 山内敏正 ( 担当： 共著 )
診断と治療社 2023年05月 ISBN: 9784787825933
学術書
学術関係受賞 【 表示 ／ 非表示 】
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Young Investigator Award
2017年10月 日本糖尿病合併症学会 脂肪細胞における転写・エピゲノム制御と糖・脂質・エネルギー代謝における意義
受賞者： 脇 裕典 -
研究奨励賞
2017年09月 日本体質医学会 脂肪細胞における転写・エピゲノム制御と生活習慣病における意義
受賞者： 脇 裕典
科研費（文科省・学振）獲得実績 【 表示 ／ 非表示 】
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新規脂肪前駆細胞群のエピジェネティック制御機構の解明
挑戦的研究(萌芽)
研究期間: 2021年07月 - 2023年03月 代表者: 脇 裕典
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新規脂肪前駆細胞群のエピジェネティック制御機構の解明
挑戦的研究(萌芽)
研究期間: 2021年07月 - 2023年03月 代表者: 脇 裕典
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新規脂肪前駆細胞群のエピジェネティック制御機構の解明
挑戦的研究(萌芽)
研究期間: 2021年07月 - 2023年03月 代表者: 脇 裕典
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新規脂肪前駆細胞群のエピジェネティック制御機構の解明
挑戦的研究(萌芽)
研究期間: 2021年07月 - 2023年03月 代表者: 脇 裕典
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新規脂肪前駆細胞群のエピジェネティック制御機構の解明
挑戦的研究(萌芽)
研究期間: 2021年07月 - 2023年03月 代表者: 脇 裕典
学会等発表 【 表示 ／ 非表示 】
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Hironori Waki [招待有り]
IDF congress 2023 2023年12月 - 2023年12月 IDF
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脇裕典, 清水辰徳, 大口弥里, 斎藤楓, 平池勇雄, 青山倫久, 堤修一, 安田和基, 戸邉一之, 成田伸太郎, 羽渕友則, 山内敏正 [招待有り]
第44回 日本肥満学会 第41回 日本肥満症治療学会学術集会 2023年11月 - 2023年11月
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よく知って上手につきあう肥満と糖尿病 ～最近のトピックス～
脇 裕典 [招待有り]
第48回地域の医療を考える集い 2023年10月 - 2023年10月
学会・委員会等活動 【 表示 ／ 非表示 】
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日本糖尿病協会
2024年04月-継続中代議員
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日本肥満学会
2024年03月-継続中教育委員会 委員
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日本肥満学会
2024年03月-継続中若手委員会委員長
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日本糖尿病学会
2022年05月-継続中英文誌編集委員会, Diabetology International, associate editor
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特定非営利活動法人 秋田県糖尿病対策推進協議会
2022年05月-継続中理事長
学外の社会活動（高大・地域連携等） 【 表示 ／ 非表示 】
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東京大学医学部附属病院 患者会かけはしの会（東京都糖尿病協会所属）会長
東京大学医学部附属病院 糖尿病・代謝内科
2009年02月-2021年05月 -
東京大学医学部附属病院 患者会ひまわりの会（１型糖尿病・ミトコンドリア糖尿病）会長
東京大学医学部附属病院 糖尿病・代謝内科
2009年02月-2021年05月