Faculty Profiles - SONE, Hirohito

Papers - SONE, Hirohito

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Rhomboid protease RHBDL4/RHBDD1 cleaves SREBP-1c at endoplasmic reticulum monitoring and regulating fatty acids. International journal

Song-Iee Han, Masanori Nakakuki, Yoshimi Nakagawa, Yunong Wang, Masaya Araki, Yuta Yamamoto, Hiroaki Tokiwa, Hiroyuki Takeda, Yuhei Mizunoe, Kaori Motomura, Hiroshi Ohno, Kenta Kainoh, Yuki Murayama, Yuichi Aita, Yoshinori Takeuchi, Yoshinori Osaki, Takafumi Miyamoto, Motohiro Sekiya, Takashi Matsuzaka, Naoya Yahagi, Hirohito Sone, Hiroaki Daitoku, Ryuichiro Sato, Hiroyuki Kawano, Hitoshi Shimano

PNAS nexus 2 ( 11 ) pgad351 2023.11

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

The endoplasmic reticulum (ER)-embedded transcription factors, sterol regulatory element-binding proteins (SREBPs), master regulators of lipid biosynthesis, are transported to the Golgi for proteolytic activation to tune cellular cholesterol levels and regulate lipogenesis. However, mechanisms by which the cell responds to the levels of saturated or unsaturated fatty acids remain underexplored. Here, we show that RHBDL4/RHBDD1, a rhomboid family protease, directly cleaves SREBP-1c at the ER. The p97/VCP, AAA-ATPase complex then acts as an auxiliary segregase to extract the remaining ER-embedded fragment of SREBP-1c. Importantly, the enzymatic activity of RHBDL4 is enhanced by saturated fatty acids (SFAs) but inhibited by polyunsaturated fatty acids (PUFAs). Genetic deletion of RHBDL4 in mice fed on a Western diet enriched in SFAs and cholesterol prevented SREBP-1c from inducing genes for lipogenesis, particularly for synthesis and incorporation of PUFAs, and secretion of lipoproteins. The RHBDL4-SREBP-1c pathway reveals a regulatory system for monitoring fatty acid composition and maintaining cellular lipid homeostasis.

DOI： 10.1093/pnasnexus/pgad351

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Single-cell transcriptome profiling of pancreatic islets from early diabetic mice identifies Anxa10 for Ca2+ allostasis toward β-cell failure. International journal

Kaori Motomura, Takashi Matsuzaka, Shigeyuki Shichino, Tatsuro Ogawa, Hao Pan, Takuya Nakajima, Yasuhito Asano, Toshitsugu Okayama, Tomoyo Takeuchi, Hiroshi Ohno, Song-Iee Han, Takafumi Miyamoto, Yoshinori Takeuchi, Motohiro Sekiya, Hirohito Sone, Naoya Yahagi, Yoshimi Nakagawa, Tatsuya Oda, Satoshi Ueha, Kazuho Ikeo, Atsushi Ogura, Kouji Matsushima, Hitoshi Shimano

Diabetes 2023.10

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

Type 2 diabetes (T2D) is a progressive disorder denoted by hyperglycemia and impaired insulin secretion. Although a decrease in β-cell function and mass is a well-known trigger for diabetes, the comprehensive mechanism is still unidentified. Here we carried out single-cell RNA sequencing (scRNA-seq) of pancreatic islets from prediabetic and diabetic db/db mice, an animal model of T2D. We discovered a diabetes-specific transcriptome landscape of endocrine and nonendocrine cell types with subpopulations of β and α cells. We recognized a new prediabetic gene, Anxa10, that was induced by, and regulated Ca2+ influx from metabolic stresses. Anxa10-overexpressed β cells displayed suppression of glucose-stimulated intracellular Ca2+ elevation and potassiuminduced insulin secretion. Pseudotime analysis of β cells predicted this Ca2+-surge responder-cluster proceeded to mitochondria dysfunction and also endoplasmic reticulum stress. Other trajectories comprised dedifferentiation and transdifferentiation, emphasizing acinar-like cells in diabetic islets. Altogether, our data provides a new insight into Ca2+ allostasis and β cell failure processes.

DOI： 10.2337/db23-0212

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妊娠糖尿病既往女性のフォローアップに関する診療ガイドライン

平松祐司, 杉山隆, 安日一郎, 曽根博仁, 菊池透, 瀧本秀美, 安田和基, 小川佳宏, 荒田尚子, 和栗雅子, 橋本貢士, 宮越敬, 山下洋, 鳴本敬一郎, 青山友子, 山本周美, 川崎麻紀, Obaidur Rahman, 川嵜有紀, 大田えりか, 内潟安子, 川崎英二, 守屋達美, 上塘正人, 田中幹二, 増山寿, 森川守, 楠田聡, 杉原茂孝, 清水一紀, 武田純, 原島伸一, 柳澤慶香, 田中佳代, 人見麻美子, 板倉敦夫, 寺内康夫, 平成30年度日本医療研究開発機構日本医療研究開発機構女性の健康の包括的支援実用化研究事業「妊娠糖尿病女性における出産後の糖尿病・メタボリックシンドローム発症のリスク因子同定と予防介入に関する研究」研究班, 一般社団法人日本糖尿病・妊娠学会

糖尿病と妊娠 23 ( 別冊 ) 1 - 95 2023.10

握力、閉眼片足立ち、立位体前屈による総合体力指標は代謝性疾患のスクリーニングに有用である

佐藤隆明, 藤原和哉, 山田万祐子, 張かおり, 矢口雄大, 山本正彦, 北澤勝, 石黒創, 大澤妙子, 山田貴穂, 加藤公則, 曽根博仁

日本臨床運動療法学会学術集会プログラム・抄録集 42回 61 - 61 2023.10

妊娠糖尿病既往女性のフォローアップに関する診療ガイドライン

糖尿病と妊娠 23 ( 別冊 ) 1 - 95 2023.10

血糖コントロールと妊娠合併症リスクとの量反応関係メタ回帰分析

児玉暁, 山田貴穂, 柳生田紀子, 谷内洋子, 堀川千嘉, 大澤妙子, 北澤勝, 藤原和哉, 西島浩二, 曽根博仁

糖尿病と妊娠 23 ( 3 ) S - 109 2023.10

WT1ペプチドワクチン投与後10年間以上にわたり持続するWT1特異的な細胞傷害性T細胞

諏訪部達也, 柴崎康彦, 田村秀, 片桐隆幸, 井田桃里, 布施香子, 牛木隆志, 曽根博仁, 成田美和子, 増子正義

日本血液学会学術集会 85回 117 - 117 2023.10

同種移植後day30の末梢血CD8TN、CD4TEM割合は急性GVHD発症のバイオマーカーとなる

片桐隆幸, 古山悠里, 米沢穂高, 諏訪部達也, 布施香子, 柴崎康彦, 瀧澤淳, 曽根博仁, 増子正義

日本血液学会学術集会 85回 880 - 880 2023.10

規制改革特区を活用したGDM妊婦の産後12週以降の管理の全国一律保健適応化の実現

牧尉太, 衛藤英理子, 宮越敬, 曽根博仁, 安日一郎, 杉山隆, 増山寿

糖尿病と妊娠 23 ( 3 ) S - 125 2023.10

単一施設における節外性NK/T細胞リンパ腫、鼻腔(ENKL)における26例の後方視的解析 EBV-DNA定量の有用性

山田隆, 古山悠里, 水戸部正樹, 米沢穂高, 鈴木隆晴, 諏訪部達也, 片桐隆幸, 河本啓介, 布施香子, 柴崎康彦, 増子正義, 大島孝一, 曽根博仁, 瀧澤淳

日本血液学会学術集会 85回 294 - 294 2023.10

当科におけるIVLBCL22例の後方視的解析

鈴木隆晴, 水戸部正樹, 武田ルイ, 諏訪部達也, 片桐隆幸, 河本啓介, 宮腰淑子, 北嶋俊樹, 小堺貴司, 柴崎康彦, 黒田裕行, 棗田学, 大島孝一, 曽根博仁, 瀧澤淳

日本血液学会学術集会 85回 557 - 557 2023.10

心血管疾患脂肪肝の表現型,及び2型糖尿病が心不全の新規発症に与えるインパクト

松林泰弘, 藤原和哉, 山田万祐子, 佐藤隆明, 矢口雄大, 山本正彦, 石黒創, 大澤妙子, 北澤勝, 岩永みどり, 山田貴穂, 曽根博仁

糖尿病合併症 37 ( Suppl.1 ) 164 - 164 2023.9

Associations among metabolic health, weight status, and various physical fitness components in Japanese adolescents: a cross-sectional study (NICE EVIDENCE study- Agano 3). International journal

Sakiko Yoshizawa Morikawa, Yasunaga Takeda, Kazuya Fujihara, Izumi Ikeda, Ayako Kobayashi, Mariko Hatta, Yurie Mitsuma, Chika Horikawa, Hajime Ishiguro, Takaho Yamada, Yohei Ogawa, Hirohito Sone

Journal of sports sciences 41 ( 13 ) 1279 - 1289 2023.9

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

Aim was to examine associations among metabolic health, weight status, and various physical fitness (PF) components in 1744 Japanese adolescents aged 13-14. Anthropometric measurements and PF tests (20 m shuttle run test [20mSRT], handgrip strength/body mass [HG], standing long jump [SLJ], and sit ups [SU]) were administered. The bottom sex-specific quintile of PF indicated "low fit". Participants were classified as non-overweight (non-OW) or overweight/obese (OW) according to the International Obesity Task Force. Clustered metabolic risk was defined as the sum of Z scores for mean arterial pressure, non-high-density lipoprotein cholesterol, and HbA1c, divided by three, and ≥ 1 SD. Combination of weight status and scores for HG or SU were additively associated with clustered metabolic risk. Compared with the non-OW-moderate-high fit group, the OW-low HG group was 3.05 (95%CI: 1.88-4.97) times more likely to have clustered metabolic risk although risk was not significantly elevated in the OW-moderate-high HG group (1.52 [95%CI: 0.88-2.62]). A similar association was observed between OW and low SU scores but not between OW and low 20mSRT or SLJ scores. Adolescents with OW and moderate-high HG or SU scores had a lower prevalence of an unfavourable metabolic state than those with OW and low HG or SU results.

DOI： 10.1080/02640414.2023.2268358

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Genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic GVHD via suppression of T cell activity. International journal

Suguru Tamura, Hajime Ishiguro, Tatsuya Suwabe, Takayuki Katagiri, Kaori Cho, Kyoko Fuse, Yasuhiko Shibasaki, Tadahisa Mikami, Takero Shindo, Hiroshi Kitagawa, Michihiro Igarashi, Hirohito Sone, Masayoshi Masuko, Takashi Ushiki

Scientific reports 13 ( 1 ) 13098 - 13098 2023.8

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

Donor T cell activation, proliferation, differentiation, and migration are the major steps involved in graft-versus-host disease (GVHD) development following bone marrow transplantation. Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and causes immune modulation by interacting with cell growth factors and inducing cell adhesion. However, its precise effects on immune function are unclear than those of other proteoglycan families. Thus, we investigated the significance of CS within donor cells in acute GVHD development utilizing CSGalNAc T1-knockout (T1KO) mice. To determine the effects of T1KO, the mice underwent allogenic bone marrow transplantation from major histocompatibility complex-mismatched donors. While transplantation resulted in hepatic GVHD with inflammatory cell infiltration of both CD4+ and CD8+ effector memory T cells, transplantation in T1KO-donors showed milder cell infiltration and improved survival with fewer splenic effector T cells. In vitro T-cell analyses showed that the ratio of effector memory T cells was significantly lower via phorbol myristate acetate/ionomycin stimulation. Moreover, quantitative PCR analyses showed significantly less production of inflammatory cytokines, such as IFN-γ and CCL-2, in splenocytes of T1KO mice. These results suggest that reduction of CS in donor blood cells may suppress the severity of acute GVHD after hematopoietic stem cell transplantation.

DOI： 10.1038/s41598-023-40367-3

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Relationship between the magnitude of body mass index reductions and remission in patients with type 2 diabetes in real world settings: Analysis of nationwide patient registry in Japan (JDDM74) Reviewed International journal

Hirohito Sone

Diabetes, Obesity and Metabolism 2023.7

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

AIMS: To determine the association between the magnitude of weight loss and incidence of remission according to baseline characteristics in patients with diabetes in clinical settings. METHODS: In total, 39 676 Japanese patients with type 2 diabetes aged ≥18 years with glycated haemoglobin (HbA1c) ≥6.5% and/or glucose-lowering drug prescription were identified from databases of specialists' clinics from 1989 and followed until September 2022. Remission was diagnosed as maintaining HbA1c <6.5% at least 3 months after cessation of a glucose-lowering drug. Factors associated with remission were evaluated by logistic regression analysis according to weight change in 1 year (i.e. ≥10%, 7.0-9.9%, 3.0-6.9% reduction, <3% change and ≥3.0% increase). RESULTS: During the study period, 3454 remissions occurred. The rates of remission were higher in the group with the greatest reduction of body mass index (BMI) in any category examined (i.e. baseline BMI, HbA1c, duration of diabetes and treatment). The incidences of remission per 1000 person-years were about 25 and 50, respectively, for those with BMI ≥22.5 and reductions in BMI of 7.0-9.9% and ≥10% in 1 year. Remissions per 1000 person-years were 99.2 and 91.8, respectively, for those with baseline HbA1c of 6.5-6.9 and a 10% BMI reduction and those not taking glucose-lowering drugs accompanied by a 10% BMI reduction. CONCLUSIONS: Modest weight losses of 3.0-7.9% were significantly associated with remission, but a minimum of 10% weight loss would be required in addition to an early diagnosis to achieve a 10% remission rate in clinical settings. Our results implied that remission may be expected with a relatively lower BMI in an Asian population compared with that was reported in Western populations if accompanied by weight loss.

DOI： 10.1111/DOM.15206

Web of Science

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Retrospective cohort study to examine the association between serum amylase and the incidence of type 2 diabetes mellitus, Toranomon Hospital Health Management Center Study 23 (TOPICS 23). International journal

Izumi Ikeda, Kazuya Fujihara, Taeko Osawa, Yasunaga Takeda, Mariko Hatta, Yasuhiro Matsubayashi, Satoru Kodama, Yasumichi Mori, Takashi Kadowaki, Ritsuko Honda, Yasuji Arase, Hirohito Sone

BMJ open diabetes research & care 11 ( 4 ) 2023.7

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

INTRODUCTION: Low serum amylase values are cross-sectionally associated with the prevalence of type 2 diabetes mellitus (T2DM) but have not been shown to be longitudinally associated with its incidence. This retrospective cohort (ie, historical cohort) study aimed to examine the association of previously lowered levels of serum amylase with incident T2DM. RESEARCH DESIGN AND METHODS: Examined were 8316 individuals who had annual health examinations for 6 years (ie, 7 times) at the Toranomon Hospital Health Management Center. The trajectory of serum amylase as the study exposure was classified into two elements: (1) serum amylase level at entry and (2) change in serum amylase, which was expressed as the annual change rate. The annual change rate was calculated by dividing the change in the amylase values according to follow-up periods. Regression analyses were performed to examine the association between low and decreased levels of serum amylase and the incidence of T2DM. RESULTS: Analyzed were 6917 individuals who had not developed T2DM within 1 year after cohort entry. T2DM thereafter occurred in 1021 patients. Cox regression indicated that the adjusted HR (95% CI) for incident T2DM for amylase ≤57 IU/L (quintile (Q) 1) was 0.97 (0.84 to 1.13) compared with amylase ≥58 IU/L (Q2-Q5). Logistic regression indicated that the adjusted OR (95% CI) for an annual change rate of amylase ≤-2.0% (Q1) vs ≥-1.9% (Q2-Q5) was 3.53 (3.00 to 4.16). The adjusted ORs were consistently significant throughout sensitivity analyses according to baseline amylase and the combination of age, body mass index, and hemoglobin A1c. CONCLUSIONS: Results showed that not low but previously decreased serum amylase was a risk factor for T2DM, suggesting the significance of periodic examinations of serum amylase values to detect individuals at high risk of T2DM.

DOI： 10.1136/bmjdrc-2023-003482

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Enfortumab Vedotin-induced Hyperglycemia and Ileal Conduit Reconstruction-induced Metabolic Acidosis. International journal

Takaaki Sato, Hiroshi Suzuki, Yuya Asashima, Hirohito Sone

JCEM case reports 1 ( 4 ) luad092 2023.7

Language：English

We report a 76-year-old man who was treated for hyperglycemia and metabolic acidosis after chemotherapy with enfortumab vedotin and pembrolizumab administered after his surgery for bladder cancer. He had an approximately 20-year history of diabetes. His body mass index was 18.6, and he received metformin 1000 mg/day, sitagliptin 50 mg/day, mitiglinide 30 mg/day, and voglibose 0.6 mg/day with hemoglobin A1c was approximately 7%. He underwent total cystectomy and ileal conduit reconstruction. After relapse, he received chemotherapy but later developed hyperglycemia and metabolic acidosis. His hyperglycemia was caused by enfortumab vedotin, and metabolic acidosis was attributable to the ileocecal canal. These symptoms should be remembered as important complications of this standard treatment, which prompted this case report.

DOI： 10.1210/jcemcr/luad092

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エンフォルツマブによる高血糖と回腸導管による代謝性アシドーシスをきたした1例

浅島雄弥, 佐藤隆明, 佐々木知佳, 鈴木浩史, 松林泰弘, 岩永みどり, 山田貴穂, 藤原和哉, 曽根博仁

糖尿病 66 ( 7 ) 568 - 568 2023.7

劇症1型糖尿病発症時にST上昇を呈し偽性心筋梗塞と考えられた1例

佐藤駿匡, 北澤勝, 滝澤祥子, 今西明, 山田万祐子, 松林泰弘, 藤原和哉, 山田貴穂, 保屋野真, 曽根博仁

糖尿病 66 ( 7 ) 570 - 570 2023.7

329-OR: Accuracy of Dietary Records (DR) Using a Smartphone App Is Greatly Improved by User’s Adjustments Compared with Artificial Intelligence (AI) Alone

MASARU KITAZAWA, CHIKA HORIKAWA, IZUMI IKEDA, YASUNAGA TAKEDA, EFREM D. FERREIRA, MIZUKI TAKEUCHI, SAKIKO Y. MORIKAWA, KAZUYA FUJIHARA, SATORU KODAMA, HIROHITO SONE

Diabetes 72 ( Supplement_1 ) 2023.6

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

Although DR are important in managing diabetes, the traditional method, such as weighing foods and calculating nutrients, is burdensome to both patients and medical care providers. Although photo DR with smartphones using AI to identify the dish and calculate nutrients can be expected to reduce this burden, accuracy not been clarified. Furthermore, it is not clear to what extent accuracy improves when users and dietitians adjust the name of the dish and the portion consumed compared with AI only. In this study, photo DR taken with the smartphone app were analyzed by AI only, then adjusted by the users followed by further adjustments by a dietitian. We compared the nutrients calculated by AI, users, and dietitians to those by the traditional weighing method. Analyzed were 180 participants (mean age 58.7 y, BMI 26.7 kg/m2, 94/86 women/men, 22 with diabetes, energy intake [EI] 1640 kcal/day) The EIs (kcal/day) were calculated as 1502, 1619, and 1674 for AI, users, and dietitians, respectively, those were lower than that with the weighing method Spearman's rank correlation coefficients compared to the weighing method were 0.48, 0.88, and 0.88 for AI, users and dietitians, respectively, showing a weak correlation for AI and a strong correlation for users and dietitians. The user's adjustments greatly improved accuracy without increasing the burden on the dietitians.

<p></p> Disclosure

M.Kitazawa: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. C.Horikawa: None. I.Ikeda: None. Y.Takeda: None. E.D.Ferreira: None. M.Takeuchi: None. S.Y.Morikawa: None. K.Fujihara: None. S.Kodama: None.

Funding

Grants-in-Aid for Scientific Research (21K17637)

DOI： 10.2337/db23-329-or

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Papers - SONE, Hirohito