研究者業績

矢作 直也

ヤハギ ナオヤ  (Yahagi Naoya)

基本情報

所属
自治医科大学 内科学講座 内分泌代謝学部門 教授
学位
博士(医学)(東京大学)

連絡先
nyahagi-tkyumin.ac.jp
研究者番号
60420246
J-GLOBAL ID
200901002727554646
researchmap会員ID
6000006682

外部リンク

論文

 156
  • Aiko Shono, Aki Morihiro, Nobue Harada, Xerxes Seposo, Wataru Mimura, Shu-Ling Hoshi, Naoya Yahagi, Seiko Miyazaki, Masahide Kondo
    The International journal of pharmacy practice 2025年2月12日  
    OBJECTIVE: Testing with fingertip blood sampling, including HbA1c testing, has been available in community pharmacies in Japan since 2014. In 2016, the Mihara Pharmacy Association in Hiroshima Prefecture, in collaboration with the Mihara municipal government, developed a community programme that utilized the walk-in HbA1c test that could be offered by participating community pharmacies. The aim of this study was to assess whether the new programme could detect undiagnosed DM in the community and to compare groups who had and had not accessed the SHCG programme among SHCG eligible participants. METHOD: The programme includes pharmacist advice following participants conducted Hba1c testing in the pharmacy, and completing a questionnaire to collect self-reported personal data including lifestyle, demography, height, weight, and blood pressure. All those accessing the programme were included. We analysed data from fiscal years 2016 to 2018, obtained retrospectively from the questionnaires. KEY FINDINGS: The participants aged 40-74 years who were the target of a national health check programme represented 73.7% of the 1933 total unique participants. Approximately 40% of these participants did not undergo routine checkups, 23.8% had HbA1c scores ≥5.6%, and 2.7% had HbA1c scores ≥6.5%. CONCLUSIONS: The walk-in HbA1c community testing programme provided an opportunity to test the diabetes mellitus risk of residents, especially those who have missed their routine checkups. If the community programme were adopted widely, more undiagnosed populations at risk for diabetes mellitus could be detected in the early stages and the use of community resources such as pharmacists and pharmacies would be utilized.
  • Samia Karkoutly, Yoshinori Takeuchi, Zahra Mehrazad Saber, Chen Ye, Duhan Tao, Yuichi Aita, Yuki Murayama, Akito Shikama, Yukari Masuda, Yoshihiko Izumida, Takashi Matsuzaka, Yasushi Kawakami, Hitoshi Shimano, Naoya Yahagi
    Biochemical and Biophysical Research Communications 739 150594-150594 2024年12月  査読有り最終著者責任著者
  • Takehito Sugasawa, Atsushi Hirokawa, Norihiro Otani, Yasuharu Kanki, Kieu DM Nguyen, Tohru Takemasa, Koichi Watanabe, Yoshinori Takeuchi, Naoya Yahagi, Yoichiro Takahashi
    Genes 15(6) 709-709 2024年5月29日  
    With the rapid development of gene therapy technology in recent years, its abuse as a method of sports doping in athletics has become a concern. However, there is still room for improvement in gene-doping testing methods, and a robust animal model needs to be developed. Therefore, the purposes of this study were to establish a model of gene doping using recombinant adeno-associated virus vector-9, including the human erythropoietin gene (rAAV9-hEPO), and to establish a relevant testing method. First, it was attempted to establish the model using rAAV9-hEPO on mice. The results showed a significant increase in erythrocyte volume accompanied by an increase in spleen weight, confirming the validity of the model. Next, we attempted to detect proof of gene doping by targeting DNA and RNA. Direct proof of gene doping was detected using a TaqMan-qPCR assay with certain primers/probes. In addition, some indirect proof was identified in RNAs through the combination of a TB Green qPCR assay with RNA sequencing. Taken together, these results could provide the foundation for an effective test for gene doping in human athletes in the future.
  • Naoya Yamada, Tadayoshi Karasawa, Junya Ito, Daisuke Yamamuro, Kazushi Morimoto, Toshitaka Nakamura, Takanori Komada, Chintogtokh Baatarjav, Yuma Saimoto, Yuka Jinnouchi, Kazuhisa Watanabe, Kouichi Miura, Naoya Yahagi, Kiyotaka Nakagawa, Takayoshi Matsumura, Ken-Ichi Yamada, Shun Ishibashi, Naohiro Sata, Marcus Conrad, Masafumi Takahashi
    Nature communications 15(1) 2195-2195 2024年3月12日  
    Recent evidence indicates ferroptosis is implicated in the pathophysiology of various liver diseases; however, the organ-specific regulation mechanism is poorly understood. Here, we demonstrate 7-dehydrocholesterol reductase (DHCR7), the terminal enzyme of cholesterol biosynthesis, as a regulator of ferroptosis in hepatocytes. Genetic and pharmacological inhibition (with AY9944) of DHCR7 suppress ferroptosis in human hepatocellular carcinoma Huh-7 cells. DHCR7 inhibition increases its substrate, 7-dehydrocholesterol (7-DHC). Furthermore, exogenous 7-DHC supplementation using hydroxypropyl β-cyclodextrin suppresses ferroptosis. A 7-DHC-derived oxysterol metabolite, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), is increased by the ferroptosis-inducer RSL-3 in DHCR7-deficient cells, suggesting that the ferroptosis-suppressive effect of DHCR7 inhibition is associated with the oxidation of 7-DHC. Electron spin resonance analysis reveals that 7-DHC functions as a radical trapping agent, thus protecting cells from ferroptosis. We further show that AY9944 inhibits hepatic ischemia-reperfusion injury, and genetic ablation of Dhcr7 prevents acetaminophen-induced acute liver failure in mice. These findings provide new insights into the regulatory mechanism of liver ferroptosis and suggest a potential therapeutic option for ferroptosis-related liver diseases.
  • 松田 高明, 鈴木 浩明, 菅野 洋子, 鈴木 康裕, 山中 大介, 荒木 理沙, 矢作 直也, 関谷 元博, 川上 康, 大崎 芳典, 岩崎 仁, 橋本 幸一, 高橋 信一郎, 羽田 康司, 島野 仁
    日本病態栄養学会誌 27(Suppl.) S-96 2024年1月  
  • 松田 高明, 鈴木 浩明, 菅野 洋子, 鈴木 康裕, 山中 大介, 荒木 理沙, 矢作 直也, 関谷 元博, 川上 康, 大崎 芳典, 岩崎 仁, 橋本 幸一, 高橋 信一郎, 羽田 康司, 島野 仁
    日本病態栄養学会誌 27(Suppl.) S-96 2024年1月  
  • 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年11月  
    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.
  • 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年10月23日  
    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.
  • Yoshinori Takeuchi, Yuki Murayama, Yuichi Aita, Zahra Mehrazad Saber, Samia Karkoutly, Duhan Tao, Kyoka Katabami, Chen Ye, Akito Shikama, Yukari Masuda, Yoshihiko Izumida, Takafumi Miyamoto, Takashi Matsuzaka, Yasushi Kawakami, Hitoshi Shimano, Naoya Yahagi
    The FEBS journal 2023年9月13日  査読有り最終著者責任著者
    During periods of fasting, the body undergoes a metabolic shift from carbohydrate utilization to the use of fats and ketones as an energy source, as well as the inhibition of de novo lipogenesis and the initiation of gluconeogenesis in the liver. The transcription factor sterol regulatory element-binding protein-1 (SREBP-1), which plays a critical role in the regulation of lipogenesis, is suppressed during fasting, resulting in the suppression of hepatic lipogenesis. We previously demonstrated that the interaction of fasting-induced Kruppel-like factor 15 (KLF15) with liver X receptor serves as the essential mechanism for the nutritional regulation of SREBP-1 expression. However, the underlying mechanisms of KLF15 induction during fasting remain unclear. In this study, we show that the glucocorticoid receptor (GR) regulates the hepatic expression of KLF15 and, subsequently, lipogenesis through the KLF15-SREBP-1 pathway during fasting. KLF15 is necessary for the suppression of SREBP-1 by GR, as demonstrated through experiments using KLF15 knockout mice. Additionally, we show that GR is involved in the fasting response, with heightened binding to the KLF15 enhancer. It has been widely known that the hypothalamic-pituitary-adrenal (HPA) axis regulates the secretion of glucocorticoids and plays a significant role in the metabolic response to undernutrition. These findings demonstrate the importance of the HPA-axis-regulated GR-KLF15 pathway in the regulation of lipid metabolism in the liver during fasting.
  • Toshiya Matsukawa, Takashi Yagi, Tohru Uchida, Mashito Sakai, Masaru Mitsushima, Takao Naganuma, Hiroyuki Yano, Yuka Inaba, Hiroshi Inoue, Keisuke Yanagida, Masaaki Uematsu, Kazuki Nakao, Harumi Nakao, Atsu Aiba, Yoji Nagashima, Tetsuya Kubota, Naoto Kubota, Yoshihiko Izumida, Naoya Yahagi, Hiroyuki Unoki-Kubota, Yasushi Kaburagi, Shun-Ichiro Asahara, Yoshiaki Kido, Hideo Shindou, Michiko Itoh, Yoshihiro Ogawa, Shiro Minami, Yasuo Terauchi, Kazuyuki Tobe, Kohjiro Ueki, Masato Kasuga, Michihiro Matsumoto
    JCI insight 8(17) 2023年9月8日  
    Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes are interacting comorbidities of obesity, and increased hepatic de novo lipogenesis (DNL), driven by hyperinsulinemia and carbohydrate overload, contributes to their pathogenesis. Fatty acid synthase (FASN), a key enzyme of hepatic DNL, is upregulated in association with insulin resistance. However, the therapeutic potential of targeting FASN in hepatocytes for obesity-associated metabolic diseases is unknown. Here, we show that hepatic FASN deficiency differentially affects NAFLD and diabetes depending on the etiology of obesity. Hepatocyte-specific ablation of FASN ameliorated NAFLD and diabetes in melanocortin 4 receptor-deficient mice but not in mice with diet-induced obesity. In leptin-deficient mice, FASN ablation alleviated hepatic steatosis and improved glucose tolerance but exacerbated fed hyperglycemia and liver dysfunction. The beneficial effects of hepatic FASN deficiency on NAFLD and glucose metabolism were associated with suppression of DNL and attenuation of gluconeogenesis and fatty acid oxidation, respectively. The exacerbation of fed hyperglycemia by FASN ablation in leptin-deficient mice appeared attributable to impairment of hepatic glucose uptake triggered by glycogen accumulation and citrate-mediated inhibition of glycolysis. Further investigation of the therapeutic potential of hepatic FASN inhibition for NAFLD and diabetes in humans should thus consider the etiology of obesity.
  • Sekiya, Motohiro, Ma, Yang, Kainoh, Kenta, Saito, Kenji, Yamazaki, Daichi, Tsuyuzaki, Tomomi, Chen, Wanpei, Adi Putri, Putu Indah Paramita, Ohno, Hiroshi, Miyamoto, Takafumi, Takeuchi, Yoshinori, Murayama, Yuki, Sugano, Yoko, Osaki, Yoshinori, Iwasaki, Hitoshi, Yahagi, Naoya, Suzuki, Hiroaki, Motomura, Kaori, Matsuzaka, Takashi, Murata, Kazuya, Mizuno, Seiya, Takahashi, Satoru, Shimano, Hitoshi
    Cell Reports 42(8) 2023年8月  査読有り
    The adaptive increase in insulin secretion in early stages of obesity serves as a safeguard mechanism to maintain glucose homeostasis that cannot be sustained, and the eventual decompensation of β cells is a key event in the pathogenesis of diabetes. Here we describe a crucial system orchestrated by a transcriptional cofactor CtBP2. In cultured β cells, insulin gene expression is coactivated by CtBP2. Global genomic mapping of CtBP2 binding sites identifies a key interaction between CtBP2 and NEUROD1 through which CtBP2 decompacts chromatin in the insulin gene promoter. CtBP2 expression is diminished in pancreatic islets in multiple mouse models of obesity, as well as human obesity. Pancreatic β cell-specific CtBP2-deficient mice manifest glucose intolerance with impaired insulin secretion. Our transcriptome analysis highlights an essential role of CtBP2 in the maintenance of β cell integrity. This system provides clues to the molecular basis in obesity and may be targetable to develop therapeutic approaches.
  • 松田 高明, 鈴木 浩明, 菅野 洋子, 鈴木 康裕, 山中 大介, 荒木 理沙, 矢作 直也, 関谷 元博, 川上 康, 大崎 芳典, 岩崎 仁, 橋本 幸一, 高橋 伸一郎, 羽田 康司, 島野 仁
    糖尿病 66(Suppl.1) S-227 2023年4月  
  • Yasuhiro Suzuki, Takumi Tsubaki, Kensuke Nakaya, Genta Kondo, Yoshinori Takeuchi, Yuichi Aita, Yuki Murayama, Akito Shikama, Yukari Masuda, Hiroaki Suzuki, Yasushi Kawakami, Hitoshi Shimano, Tetsuaki Arai, Yasushi Hada, Naoya Yahagi
    BMC Geriatrics 23(1) 74-74 2023年2月4日  査読有り最終著者責任著者
    Abstract Background Mild cognitive impairment (MCI) is not just a prodrome to dementia, but a very important intervention point to prevent dementia caused by Alzheimer's disease (AD). It has long been known that people with AD have a higher frequency of falls with some gait instability. Recent evidence suggests that vestibular impairment is disproportionately prevalent among individuals with MCI and dementia due to AD. Therefore, we hypothesized that the measurement of balance capability is helpful to identify individuals with MCI. Methods First, we developed a useful method to evaluate balance capability as well as vestibular function using Nintendo Wii balance board as a stabilometer and foam rubber on it. Then, 49 healthy volunteers aged from 56 to 75 with no clinically apparent cognitive impairment were recruited and the association between their balance capability and cognitive function was examined. Cognitive functions were assessed by MoCA, MMSE, CDR, and TMT-A and -B tests. Results The new balance capability indicator, termed visual dependency index of postural stability (VPS), was highly associated with cognitive impairment assessed by MoCA, and the area under the receiver operating characteristic (ROC) curve was more than 0.8, demonstrating high sensitivity and specificity (app. 80% and 60%, respectively). Conclusions Early evidence suggests that VPS measured using Nintendo Wii balance board as a stabilometer helps identify individuals with MCI at an early and preclinical stage with high sensitivity, establishing a useful method to screen MCI.
  • Nurani Istiqamah, Takashi Matsuzaka, Momo Shimizu, Kaori Motomura, Hiroshi Ohno, Shiho Hasebe, Rahul Sharma, Yuka Okajima, Erika Matsuda, Song-Iee Han, Yuhei Mizunoe, Yoshinori Osaki, Yuichi Aita, Hiroaki Suzuki, Hirohito Sone, Yoshinori Takeuchi, Motohiro Sekiya, Naoya Yahagi, Yoshimi Nakagawa, Hitoshi Shimano
    BBA Advances 3 100078-100078 2023年  
    ELOVL fatty acid elongase 6 (ELOVL6) controls cellular fatty acid (FA) composition by catalyzing the elongation of palmitate (C16:0) to stearate (C18:0) and palmitoleate (C16:1n-7) to vaccinate (C18:1n-7). Although the transcriptional regulation of ELOVL6 has been well studied, the post-transcriptional regulation of ELOVL6 is not fully understood. Therefore, this study aims to evaluate the role of microRNAs (miRNAs) in regulating human ELOVL6. Bioinformatic analysis identified five putative miRNAs: miR-135b-5p, miR-135a-5p, miR-125a-5p, miR-125b-5p, and miR-22-3p, which potentially bind ELOVL6 3'-untranslated region (UTR). Results from dual-luciferase assays revealed that these miRNAs downregulate ELOVL6 by directly interacting with the 3'-UTR of ELOVL6 mRNA. Moreover, miR-135b-5p and miR-135a-5p suppress cell proliferation and migration in glioblastoma multiforme cells by inhibiting ELOVL6 at the mRNA and protein levels. Taken together, our results provide novel regulatory mechanisms for ELOVL6 at the post-transcriptional level and identify potential candidates for the treatment of patients with glioblastoma multiforme.
  • Takaaki Matsuda, Hiroaki Suzuki, Yoko Sugano, Yasuhiro Suzuki, Daisuke Yamanaka, Risa Araki, Naoya Yahagi, Motohiro Sekiya, Yasushi Kawakami, Yoshinori Osaki, Hitoshi Iwasaki, Koichi Hashimoto, Shin-Ichiro Takahashi, Yasushi Hada, Hitoshi Shimano
    Nutrients 14(19) 3917-3917 2022年9月21日  
    Although branched-chain amino acids (BCAA) are known to stimulate myofibrillar protein synthesis and affect insulin signaling and kynurenine metabolism (the latter being a metabolite of tryptophan associated with depression and dementia), the effects of BCAA supplementation on type 2 diabetes (T2D) are not clear. Therefore, a 24-week, prospective randomized open blinded-endpoint trial was conducted to evaluate the effects of supplementation of 8 g of BCAA or 7.5 g of soy protein on skeletal muscle and glycemic control as well as adverse events in elderly individuals with T2D. Thirty-six participants were randomly assigned to the BCAA group (n = 21) and the soy protein group (n = 15). Skeletal muscle mass and HbA1c, which were primary endpoints, did not change over time or differ between groups. However, knee extension muscle strength was significantly increased in the soy protein group and showed a tendency to increase in the BCAA group. Homeostasis model assessment for insulin resistance did not significantly change during the trial. Depressive symptoms were significantly improved in the BCAA group but the difference between groups was not significant. Results suggested that BCAA supplementation may not affect skeletal muscle mass and glycemic control and may improve depressive symptoms in elderly individuals with T2D.
  • Yasuhiro Suzuki, Hiroaki Suzuki, Tatsuya Ishikawa, Yasunori Yamada, Shigeru Yatoh, Yoko Sugano, Hitoshi Iwasaki, Motohiro Sekiya, Naoya Yahagi, Yasushi Hada, Hitoshi Shimano
    Scientific reports 12(1) 11965-11965 2022年7月13日  
    We aimed to investigate the status of falls and to identify important risk factors for falls in persons with type 2 diabetes (T2D) including the non-elderly. Participants were 316 persons with T2D who were assessed for medical history, laboratory data and physical capabilities during hospitalization and given a questionnaire on falls one year after discharge. Two different statistical models, logistic regression and random forest classifier, were used to identify the important predictors of falls. The response rate to the survey was 72%; of the 226 respondents, there were 129 males and 97 females (median age 62 years). The fall rate during the first year after discharge was 19%. Logistic regression revealed that knee extension strength, fasting C-peptide (F-CPR) level and dorsiflexion strength were independent predictors of falls. The random forest classifier placed grip strength, F-CPR, knee extension strength, dorsiflexion strength and proliferative diabetic retinopathy among the 5 most important variables for falls. Lower extremity muscle weakness, elevated F-CPR levels and reduced grip strength were shown to be important risk factors for falls in T2D. Analysis by random forest can identify new risk factors for falls in addition to logistic regression.
  • 升田 紫, 矢作 直也, 武内 謙憲, 和田 亘弘, 呼延 宜人, Mehrazad Saber Zahra, 沢田 義一, 村山 友樹, 會田 雄一, 西 真貴子[辰巳], 泉田 欣彦, 位高 啓史, 片岡 一則, 島野 仁, 門脇 孝, 山内 敏正, 筑波大学医学医療系ニュートリゲノミクスリサーチグループ
    糖尿病 65(Suppl.1) S-308 2022年4月  
  • Yuka Okajima, Takashi Matsuzaka, Shun Miyazaki, Kaori Motomura, Hiroshi Ohno, Rahul Sharma, Takuya Shimura, Nurani Istiqamah, Song-Iee Han, Yuhei Mizunoe, Yoshinori Osaki, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Hirohito Sone, Takafumi Miyamoto, Yuichi Aita, Yoshinori Takeuchi, Motohiro Sekiya, Naoya Yahagi, Yoshimi Nakagawa, Tsutomu Tomita, Hitoshi Shimano
    Biochimica et biophysica acta. Molecular basis of disease 1868(4) 166339-166339 2022年4月1日  
    The pancreatic islet vasculature is of fundamental importance to the β-cell response to obesity-associated insulin resistance. To explore islet vascular alterations in the pathogenesis of type 2 diabetes, we evaluated two insulin resistance models: ob/ob mice, which sustain large β-cell mass and hyperinsulinemia, and db/db mice, which progress to diabetes due to secondary β-cell compensation failure for insulin secretion. Time-dependent changes in islet vasculature and blood flow were investigated using tomato lectin staining and in vivo live imaging. Marked islet capillary dilation was observed in ob/ob mice, but this adaptive change was blunted in db/db mice. Islet blood flow volume was augmented in ob/ob mice, whereas it was reduced in db/db mice. The protein concentrations of total and phosphorylated endothelial nitric oxide synthase (eNOS) at Ser1177 were increased in ob/ob islets, while they were diminished in db/db mice, indicating decreased eNOS activity. This was accompanied by an increased retention of advanced glycation end-products in db/db blood vessels. Amelioration of diabetes by Elovl6 deficiency involved a restoration of capillary dilation, blood flow, and eNOS phosphorylation in db/db islets. Our findings suggest that the disability of islet capillary dilation due to endothelial dysfunction impairs local islet blood flow, which may play a role in the loss of β-cell function and further exacerbate type 2 diabetes.
  • Zahra Mehrazad Saber, Yoshinori Takeuchi, Yoshikazu Sawada, Yuichi Aita, Man Hei Ho, Samia Karkoutly, Duhan Tao, Kyoka Katabami, Chen Ye, Yuki Murayama, Akito Shikama, Yukari Masuda, Yoshihiko Izumida, Takafumi Miyamoto, Takashi Matsuzaka, Takehito Sugasawa, Kazuhiro Takekoshi, Yasushi Kawakami, Hitoshi Shimano, Naoya Yahagi
    Biochemical and biophysical research communications 582 35-42 2021年12月10日  査読有り最終著者責任著者
    High protein diet (HPD) is an affordable and positive approach in prevention and treatment of many diseases. It is believed that transcriptional regulation is responsible for adaptation after HPD feeding and Kruppel-like factor 15 (KLF15), a zinc finger transcription factor that has been proved to perform transcriptional regulation over amino acid, lipid and glucose metabolism, is known to be involved at least in part in this HPD response. To gain more insight into molecular mechanisms by which HPD controls expressions of genes involved in amino acid metabolism in the liver, we performed RNA-seq analysis of mice fed HPD for a short period (3 days). Compared to a low protein diet, HPD feeding significantly increased hepatic expressions of enzymes involved in the breakdown of all the 20 amino acids. Moreover, using KLF15 knockout mice and in vivo Ad-luc analytical system, we were able to identify Cth (cystathionine gamma-lyase) as a new target gene of KLF15 transcription as well as Ast (aspartate aminotransferase) as an example of KLF15-independent gene despite its remarkable responsiveness to HPD. These findings provide us with a clue to elucidate the entire transcriptional regulatory mechanisms of amino acid metabolic pathways.
  • Yoshinori Takeuchi, Naoya Yahagi, Yuichi Aita, Zahra Mehrazad-Saber, Man Hei Ho, Yiren Huyan, Yuki Murayama, Akito Shikama, Yukari Masuda, Yoshihiko Izumida, Takafumi Miyamoto, Takashi Matsuzaka, Yasushi Kawakami, Hitoshi Shimano
    iScience 24(12) 103446-103446 2021年12月  査読有り責任著者
    KLF15 is a transcription factor that plays an important role in the activation of gluconeogenesis from amino acids as well as the suppression of lipogenesis from glucose. Here we identified the transcription start site of liver-specific KLF15 transcript and showed that FoxO1/3 transcriptionally regulates Klf15 gene expression by directly binding to the liver-specific Klf15 promoter. To achieve this, we performed a precise in vivo promoter analysis combined with the genome-wide transcription-factor-screening method "TFEL scan", using our original Transcription Factor Expression Library (TFEL), which covers nearly all the transcription factors in the mouse genome. Hepatic Klf15 expression is significantly increased via FoxOs by attenuating insulin signaling. Furthermore, FoxOs elevate the expression levels of amino acid catabolic enzymes and suppress SREBP-1c via KLF15, resulting in accelerated amino acid breakdown and suppressed lipogenesis during fasting. Thus, the FoxO-KLF15 pathway contributes to switching the macronutrient flow in the liver under the control of insulin.
  • 鈴木 康裕, 矢作 直也, 椿 拓海, 中谷 謙佑, 柳澤 幸夫, 新井 哲明, 羽田 康司
    Dementia Japan 35(4) 632-632 2021年10月  
  • Han SI, Nakakuki M, Nakagawa Y, Wang Y, Araki M, Yamamoto Y, Tokiwa H, Takeda H, Mizunoe Y, Motomura K, Ohno H, Murayama Y, Aita Y, Takeuchi Y, Osaki Y, Miyamoto T, Sekiya M, Matsuzaka T, Yahagi N, Sone H, Kawano H, Shimano H
    bioRxiv 2021年8月  
  • Takafumi Miyamoto, Hideki Uosaki, Yuhei Mizunoe, Song-Iee Han, Satoi Goto, Daisuke Yamanaka, Masato Masuda, Yosuke Yoneyama, Hideki Nakamura, Naoko Hattori, Yoshinori Takeuchi, Hiroshi Ohno, Motohiro Sekiya, Takashi Matsuzaka, Fumihiko Hakuno, Shin-Ichiro Takahashi, Naoya Yahagi, Koichi Ito, Hitoshi Shimano
    Cell Reports Methods 1(4) 100052-100052 2021年7月  
    Engineered synthetic biomolecular devices that integrate elaborate information processing and precisely regulate living cell behavior have potential in various applications. Although devices that directly regulate key biomolecules constituting inherent biological systems exist, no devices have been developed to control intracellular membrane architecture, contributing to the spatiotemporal functions of these biomolecules. This study developed a synthetic biomolecular device, termed inducible counter mitochondrial morphology (iCMM), to manipulate mitochondrial morphology, an emerging informative property for understanding physiopathological cellular behaviors, on a minute timescale by using a chemically inducible dimerization system. Using iCMM, we determined cellular changes by altering mitochondrial morphology in an unprecedented manner. This approach serves as a platform for developing more sophisticated synthetic biomolecular devices to regulate biological systems by extending manipulation targets from conventional biomolecules to mitochondria. Furthermore, iCMM might serve as a tool for uncovering the biological significance of mitochondrial morphology in various physiopathological cellular processes.
  • Aiko Shono, Masahide Kondo, Shu-Ling Hoshi, Reiko Okubo, Naoya Yahagi
    Research in social & administrative pharmacy : RSAP 17(2) 368-371 2021年2月  最終著者
    In Japan, a new opportunistic community-based walk-in HbA1c testing program at pharmacies was enabled in 2014. An economic evaluation of this program from societal perspective has previously been published. This study examines the effect of a subsidy program for walk-in HbA1c-testing at community pharmacies in Japan on public health care expenditure by conducting a budget impact analysis from payer's perspective. The study focused on Adachi Ward in Tokyo, where a pioneering subsidy program was implemented. It examined the budget impact of the subsidy program over a 15 years. The total subsidy paid by the local authority during the first year was 2909 USD. Public expenditure remained positive for the first five years before becoming negative in the sixth year, eventually resulting in savings of 221,000 USD in the 15th year. The cost of treating type 2 diabetes that is detected early is offset by a reduction in expensive treatments for complicated cases. Subsidizing walk-in fingertip HbA1c testing in community pharmacies is likely to result in a significant reduction in public expenditure over the mid-to long term. Our result suggests that a similar strategy in other areas could also have a potentially favorable budget impact.
  • Naoya Yahagi, Yoshinori Takeuchi
    F1000Research 10 51-51 2021年2月  査読有り筆頭著者責任著者
    The identification of upstream transcription factors regulating the expression of a gene is generally not an easy process.  To facilitate this task, we constructed an expression cDNA library named Transcription Factor Expression Library (TFEL), which is composed of nearly all the transcription factors in the mouse genome. Genome-wide screening using this library (TFEL scan method) enables us to easily identify transcription factors controlling any given promoter or enhancer of interest in a chromosomal context-dependent manner. Thus, TFEL scan method is a powerful approach to explore transcriptional regulatory networks.
  • Manabu Midorikawa, Hiroaki Suzuki, Yasuhiro Suzuki, Kazuyoshi Yamauchi, Hiroyuki Sato, Kiyotaka Nemoto, Yoko Sugano, Hitoshi Iwasaki, Motohiro Sekiya, Shigeru Yatoh, Naoya Yahagi, Yasushi Hada, Tetsuaki Arai, Hitoshi Shimano
    Journal of diabetes research 2021 9961612-9961612 2021年  
    Aim: We investigated the relationship between cognitive function and olfactory and physical functions in middle-aged persons with and without type 2 diabetes (T2D) to examine the potential of olfactory and physical functions as biomarkers for early cognitive impairment. Methods: Enrolled were 70 T2D patients (age 40 to <65 y) and 81 age-matched control participants without diabetes. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCA), Trail Making Test parts A and B (TMT-A/-B), Wisconsin Card Sorting Test (WCST), Quick Inventory of Depressive Symptomatology Self-Report (QIDS), and Starkstein Apathy Scale (SAS). Multiple linear regression analyses were performed. Results: Odor identification was an independent determinant shown in the results of the TMT-A in the entire participant group and was independently associated with the MoCA and TMT-B in the T2D group. Balance capability assessed with a stabilometer was independently associated with all cognitive function tests except for QISD and SAS in the entire participant group and the T2D group and was independently associated with TMT-A in the control group. Knee extension strength was independently associated with the SAS in the entire participant group and the T2D group. Conclusions: Odor identification, balance capability, and knee extension strength were potential markers for cognitive decline in middle-aged persons with T2D.
  • Takeito Sugasawa, Kai Aoki, Koki Yanazawa, Ryo Hagino, Shinsuke Tamai, Koichi Watanabe, Tohru Takemasa, Yoshinori Takeuchi, Yuichi Aita, Naoya Yahagi, Yasuko Yoshida, Tomoaki Kuji, Yasuhiro Shishikura, Seiko Ono, Takuro Nakano, Ban Kai, Kaoru Takeuchi, Yasushi Kawamai, Kazuhiro Takekoshi
    2020年5月23日  
    The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the artificial regulation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. First, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan-qPCR assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans.
  • Motohiro Sekiya, Takaaki Matsuda, Yuki Yamamoto, Yasuhisa Furuta, Mariko Ohyama, Yuki Murayama, Yoko Sugano, Yoshinori Ohsaki, Hitoshi Iwasaki, Naoya Yahagi, Shigeru Yatoh, Hiroaki Suzuki, Hitoshi Shimano
    BMC medical genetics 21(1) 91-91 2020年5月6日  
    BACKGROUND: Renal hypouricemia (RHUC) is a hereditary disorder where mutations in SLC22A12 gene and SLC2A9 gene cause RHUC type 1 (RHUC1) and RHUC type 2 (RHUC2), respectively. These genes regulate renal tubular reabsorption of urates while there exist other genes counterbalancing the net excretion of urates including ABCG2 and SLC17A1. Urate metabolism is tightly interconnected with glucose metabolism, and SLC2A9 gene may be involved in insulin secretion from pancreatic β-cells. On the other hand, a myriad of genes are responsible for the impaired insulin secretion independently of urate metabolism. CASE PRESENTATION: We describe a 67 year-old Japanese man who manifested severe hypouricemia (0.7 mg/dl (3.8-7.0 mg/dl), 41.6 μmol/l (226-416 μmol/l)) and diabetes with impaired insulin secretion. His high urinary fractional excretion of urate (65.5%) and low urinary C-peptide excretion (25.7 μg/day) were compatible with the diagnosis of RHUC and impaired insulin secretion, respectively. Considering the fact that metabolic pathways regulating urates and glucose are closely interconnected, we attempted to delineate the genetic basis of the hypouricemia and the insulin secretion defect observed in this patient using whole exome sequencing. Intriguingly, we found homozygous Trp258* mutations in SLC22A12 gene causing RHUC1 while concurrent mutations reported to be associated with hyperuricemia were also discovered including ABCG2 (Gln141Lys) and SLC17A1 (Thr269Ile). SLC2A9, that also facilitates glucose transport, has been implicated to enhance insulin secretion, however, the non-synonymous mutations found in SLC2A9 gene of this patient were not dysfunctional variants. Therefore, we embarked on a search for causal mutations for his impaired insulin secretion, resulting in identification of multiple mutations in HNF1A gene (MODY3) as well as other genes that play roles in pancreatic β-cells. Among them, the Leu80fs in the homeobox gene NKX6.1 was an unreported mutation. CONCLUSION: We found a case of RHUC1 carrying mutations in SLC22A12 gene accompanied with compensatory mutations associated with hyperuricemia, representing the first report showing coexistence of the mutations with opposed potential to regulate urate concentrations. On the other hand, independent gene mutations may be responsible for his impaired insulin secretion, which contains novel mutations in key genes in the pancreatic β-cell functions that deserve further scrutiny.
  • Takehito Sugasawa, Tomoaki Kuji, Kai Aoki, Koki Yanazawa, Akiko Takenouchi, Makoto Watanabe, Yoshiya Tome, Yoshinori Takeuchi, Yuichi Aita, Naoya Yahagi, Yasuhiro Shishikura, Seiko Ono, Yasuko Yoshida, Yasushi Kawakami, Kazuhiro Takekoshi
    Biomedicines 8(3) 2020年3月10日  査読有り
    The aim of this study was to clarify degradation characteristics in each tissue of the knee complex of a medial meniscectomy (MMx)-induced knee osteoarthritis (KOA) animal model using classical methods and an alternative comprehensive evaluation method called contrast-enhanced X-ray micro-computed tomography (CEX-μCT), which was developed in the study. Surgical MMx was performed in the right knee joints of five male Wistar rats to induce KOA. At four weeks post-surgery, the synovitis was evaluated using quantitative polymerase chain reaction (qPCR). Degradations of the articular cartilage of the tibial plateau were evaluated using classical methods and CEX-μCT. Evaluation of the synovitis demonstrated significantly increased expression levels of inflammation-associated marker genes in MMx-treated knees compared with those in sham-treated knees. Evaluation of the articular cartilage using classical methods showed that MMx fully induced degradation of the cartilage. Evaluation using CEX-μCT showed that local areas of the medial cartilage of the tibial plateau were significantly reduced in MMx-treated knees compared with those in sham-treated knees. On the other hand, total cartilage volumes were significantly increased in MMx-treated knees. On the basis of the findings of this study, the method could be relevant to study new treatments in KOA research.
  • Kai Aoki, Takehito Sugasawa, Kouki Yanazawa, Koichi Watanabe, Tohru Takemasa, Yoshinori Takeuchi, Yuichi Aita, Naoya Yahagi, Yasuko Yoshida, Tomoaki Kuji, Nanami Sekine, Kaoru Takeuchi, Haruna Ueda, Yasushi Kawakami, Kazuhiro Takekoshi
    PeerJ 8 e8595 2020年  査読有り
    Background: With the rapid progress of genetic engineering and gene therapy methods, the World Anti-Doping Agency has raised concerns regarding gene doping, which is prohibited in sports. However, there is no standard method available for detecting transgenes delivered by injection of naked plasmids. Here, we developed a detection method for detecting transgenes delivered by injection of naked plasmids in a mouse model that mimics gene doping. Methods: Whole blood from the tail tip and one piece of stool were used as pre-samples of injection. Next, a plasmid vector containing the human erythropoietin (hEPO) gene was injected into mice through intravenous (IV), intraperitoneal (IP), or local muscular (IM) injection. At 1, 2, 3, 6, 12, 24, and 48 h after injection, approximately 50 µL whole blood was collected from the tail tip. One piece of stool was collected at 6, 12, 24, and 48 h. From each sample, total DNA was extracted and transgene fragments were analyzed by Taqman quantitative PCR (qPCR) and SYBR green qPCR. Results: In whole blood DNA samples evaluated by Taqman qPCR, the transgene fragments were detected at all time points in the IP sample and at 1, 2, 3, 6, and 12 h in the IV and IM samples. In the stool-DNA samples, the transgene fragments were detected at 6, 12, 24, and 48 h in the IV and IM samples by Taqman qPCR. In the analysis by SYBR green qPCR, the transgene fragments were detected at some time point in both specimens; however, many non-specific amplicons were detected. Conclusions: These results indicate that transgene fragments evaluated after each injection method of naked plasmids were detected in whole-blood and stool DNA samples. These findings may facilitate the development of methods for detecting gene doping.
  • Suzuki, Y, Suzuki, H, Ishikawa, T, Yamada, Y, Yatoh, S, Sugano, Y, Iwasaki, H, Sekiya, M, Yahagi, N, Hada, Y, Shimano, H
    DIABETOLOGIA 62(1:SI) S509-S509 2019年9月  
  • Matsuzaka T, Kuba M, Koyasu S, Yamamoto Y, Motomura K, Arulmozhiraja S, Ohno H, Sharma R, Shimura T, Okajima Y, Han SI, Aita Y, Mizunoe Y, Osaki Y, Iwasaki H, Yatoh S, Suzuki H, Sone H, Takeuchi Y, Yahagi N, Miyamoto T, Sekiya M, Nakagawa Y, Ema M, Takahashi S, Tokiwa H, Shimano H
    Hepatology (Baltimore, Md.) 71(5) 1609-1625 2019年9月  査読有り
  • Takehito Sugasawa, Kai Aoki, Koichi Watanabe, Koki Yanazawa, Tohru Natsume, Tohru Takemasa, Kaori Yamaguchi, Yoshinori Takeuchi, Yuichi Aita, Naoya Yahagi, Yasuko Yoshida, Katsuyuki Tokinoya, Nanami Sekine, Kaoru Takeuchi, Haruna Ueda, Yasushi Kawakami, Satoshi Shimizu, Kazuhiro Takekoshi
    Genes 10(6) 2019年6月8日  査読有り
    With the rapid progress of genetic engineering and gene therapy, the World Anti-Doping Agency has been alerted to gene doping and prohibited its use in sports. However, there is no standard method available yet for the detection of transgenes delivered by recombinant adenoviral (rAdV) vectors. Here, we aim to develop a detection method for transgenes delivered by rAdV vectors in a mouse model that mimics gene doping. These rAdV vectors containing the mCherry gene was delivered in mice through intravenous injection or local muscular injection. After five days, stool and whole blood samples were collected, and total DNA was extracted. As additional experiments, whole blood was also collected from the mouse tail tip until 15 days from injection of the rAdv vector. Transgene fragments from different DNA samples were analyzed using semi-quantitative PCR (sqPCR), quantitative PCR (qPCR), and droplet digital PCR (ddPCR). In the results, transgene fragments could be directly detected from blood cell fraction DNA, plasma cell-free DNA, and stool DNA by qPCR and ddPCR, depending on specimen type and injection methods. We observed that a combination of blood cell fraction DNA and ddPCR was more sensitive than other combinations used in this model. These results could accelerate the development of detection methods for gene doping.
  • Takehito Sugasawa, Tome Yoshiya, Yoshinori Takeuchi, Naoya Yahagi, Rahul Sharma, Yuichi Aita, Yasuko Yoshida, Katuyuki Tokinoya, Nanami Sekine, Kaoru Takeuchi, Haruna Ueda, Reina Maruyama, Shohei Morita, Yasushi Kawamai, Kazuhiro Takekoshi
    2019年4月25日  査読有り
    Local cryotherapy is widely used as a treatment for sports-related skeletal muscle injury. However, its molecular mechanisms are unknown. To clarify these mechanisms, in this study, we applied one to three 15-min cold stimulations at 4 &amp;deg;C to various cell lines (in vitro), the tibialis anterior (TA) muscle (ex vivo), and mouse limbs (in vivo). In the in vitro assay, cAMP response element-binding protein 1 (CREB1) was markedly phosphorylated (as pCREB1) and CREB-binding protein (CBP) was recruited to pCREB-1 in response to two or three cold stimulations. In a reporter assay with the cAMP-responsive element, the signals significantly increased after two to three cold stimulations at 4 &amp;deg;C. In the ex vivo study, CREB-targeting genes were significantly upregulated following two or three cold stimulations. The in vivo experiment disclosed that cold stimulation of a mouse limb for 9 days significantly increased mitochondrial DNA copy number and upregulated genes such as Pgc-1&amp;alpha; involved in mitochondrial biogenesis. The foregoing results suggest that local cryotherapy increases CREB transcription and upregulates CREB-targeting genes in a manner dependent on cold stimulation frequency and duration. This information may serve as an impetus for further investigations into local cryotherapy as a treatment for sports-related skeletal muscle trauma.
  • Sharma R, Matsuzaka T, Kaushik MK, Sugasawa T, Ohno H, Wang Y, Motomura K, Shimura T, Okajima Y, Mizunoe Y, Ma Y, Saber ZM, Iwasaki H, Yatoh S, Suzuki H, Aita Y, Han SI, Takeuchi Y, Yahagi N, Miyamoto T, Sekiya M, Nakagawa Y, Shimano H
    Scientific reports 9(1) 5169 2019年3月  査読有り
  • Murayama Y, Yahagi N, Takeuchi Y, Aita Y, Mehrazad Saber Z, Wada N, Li E, Piao X, Sawada Y, Shikama A, Masuda Y, Nishi-Tatsumi M, Kubota M, Izumida Y, Miyamoto T, Sekiya M, Matsuzaka T, Nakagawa Y, Sugano Y, Iwasaki H, Kobayashi K, Yatoh S, Suzuki H, Yagyu H, Kawakami Y, Shimano H
    FEBS letters 593(4) 423-432 2019年2月  査読有り責任著者
  • Suzuki, H, Araki, R, Sasaki-Fukatsu, K, Fujie, K, Sekiya, M, Nakagawa, Y, Matsuzaka, T, Nakata, Y, Yahagi, N, Hashimoto, K, Shimano, H
    DIABETOLOGIA 61(1) S338-S338 2018年10月  
  • 松田 えりか, 松田 高明, 古田 泰久, 佐伯 祐典, 菅野 洋子, 岩崎 仁, 関谷 元博, 矢藤 繁, 矢作 直也, 加藤 貴康, 後藤 行延, 鈴木 浩明, 島野 仁
    日本内分泌学会雑誌 94(2) 709-709 2018年9月  
  • Shoko Furukawa, Hiroaki Suzuki, Kazuya Fujihara, Kazuto Kobayashi, Hitoshi Iwasaki, Yoko Sugano, Shigeru Yatoh, Motohiro Sekiya, Naoya Yahagi, Hitoshi Shimano
    Diabetes Research and Clinical Practice 141 237-243 2018年7月1日  査読有り
  • Hiroshi Ohno, Takashi Matsuzaka, Nie Tang, Rahul Sharma, Kaori Motomura, Takuya Shimura, Aoi Satoh, Song-Iee Han, Yoshinori Takeuchi, Yuichi Aita, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Motohiro Sekiya, Yoshimi Nakagawa, Hirohito Sone, Naoya Yahagi, Nobuhiro Yamada, Yoshikazu Higami, Hitoshi Shimano
    Endocrinology 159(6) 2308-2323 2018年6月1日  査読有り
  • Aiko Shono, Masahide Kondo, Shuling Hoshi, Reiko Okubo, Naoya Yahagi
    Diabetes Care 41(6) 1218-1226 2018年6月1日  査読有り最終著者
  • 會田 雄一, 矢作 直也, 武内 謙憲, 朴 賢英, 呼延 宜人, 和田 亘弘, 李 恩旭, 村山 友樹, 沢田 義一, 志鎌 明人, 升田 紫, 泉田 欣彦, 関谷 元博, 中川 嘉, 松坂 賢, 川上 康, 島野 仁
    糖尿病 61(Suppl.1) S-313 2018年4月  
  • Xianying Piao, Naoya Yahagi, Yoshinori Takeuchi, Yuichi Aita, Yuki Murayama, Yoshikazu Sawada, Akito Shikama, Yukari Masuda, Makiko Nishi-Tatsumi, Midori Kubota, Yoshihiko Izumida, Motohiro Sekiya, Takashi Matsuzaka, Yoshimi Nakagawa, Yoko Sugano, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Hiroaki Suzuki, Hiroaki Yagyu, Yasushi Kawakami, Hitoshi Shimano
    FEBS Letters 592(3) 422-433 2018年2月1日  査読有り責任著者
  • Yoshikazu Sawada, Yoshihiko Izumida, Yoshinori Takeuchi, Yuichi Aita, Nobuhiro Wada, EnXu Li, Yuki Murayama, Xianying Piao, Akito Shikama, Yukari Masuda, Makiko Nishi-Tatsumi, Midori Kubota, Motohiro Sekiya, Takashi Matsuzaka, Yoshimi Nakagawa, Yoko Sugano, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Hiroaki Suzuki, Hiroaki Yagyu, Yasushi Kawakami, Takashi Kadowaki, Hitoshi Shimano, Naoya Yahagi
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 493(1) 40-45 2017年11月  査読有り最終著者責任著者
  • Takei K, Han SI, Murayama Y, Satoh A, Oikawa F, Ohno H, Osaki Y, Matsuzaka T, Sekiya M, Iwasaki H, Yatoh S, Yahagi N, Suzuki H, Yamada N, Nakagawa Y, Shimano H
    Journal of diabetes investigation 8(4) 446-452 2017年7月1日  査読有り
  • Zhao H, Matsuzaka T, Nakano Y, Motomura K, Tang N, Yokoo T, Okajima Y, Han SI, Takeuchi Y, Aita Y, Iwasaki H, Yatoh S, Suzuki H, Sekiya M, Yahagi N, Nakagawa Y, Sone H, Yamada N, Shimano H
    Diabetes 66(7) 1833-1846 2017年7月  査読有り
  • Zhao, Hui, Matsuzaka, Takashi, Nakano, Yuta, Motomura, Kaori, Tang, Nie, Yokoo, Tomotaka, Okajima, Yuka, Han, Song-Iee, Takeuchi, Yoshinori, Aita, Yuichi, Iwasaki, Hitoshi, Yatoh, Shigeru, Suzuki, Hiroaki, Sekiya, Motohiro, Yahagi, Naoya, Nakagawa, Yoshimi, Sone, Hirohito, Yamada, Nobuhiro, Shimano, Hitoshi
    Diabetes 66(7) 1833-1846 2017年7月  
  • Makiko Nishi-Tatsumi, Naoya Yahagi, Yoshinori Takeuchi, Naoki Toya, Ayako Takarada, Yuki Murayama, Yuichi Aita, Yoshikazu Sawada, Xiaoying Piao, Yukari Oya, Akito Shikama, Yukari Masuda, Midori Kubota, Yoshihiko Izumida, Takashi Matsuzaka, Yoshimi Nakagawa, Motohiro Sekiya, Yoko Iizuka, Yasushi Kawakami, Takashi Kadowaki, Nobuhiro Yamada, Hitoshi Shimano
    FEBS Letters 591(7) 965-978 2017年4月1日  査読有り責任著者
  • 泉田 欣彦, 和田 亘弘, 矢作 直也, 武内 謙憲, 李 恩旭, 升田 紫, 沢田 義一, 戸谷 直樹, 朴 賢英, 會田 雄一, 志鎌 明人, 飯塚 陽子, 島野 仁, 門脇 孝
    糖尿病 60(Suppl.1) S-388 2017年4月  

MISC

 141

主要な書籍等出版物

 66

主要な講演・口頭発表等

 37

共同研究・競争的資金等の研究課題

 17