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医学部 医学科 |
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特別准教授 |
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Yamamotoya T., Hasei S., Akasaka Y., Ohata Y., Nakatsu Y., Kanna M., Fujishiro M., Sakoda H., Ono H., Kushiyama A., Misawa H., Asano T.
Scientific Reports 12 ( 1 ) 1966 2022年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
Trk-fused gene (TFG) mutations have been identified in patients with several neurodegenerative diseases. In this study, we attempted to clarify the effects of TFG deletions in motor neurons and in muscle fibers, using tissue-specific TFG knockout (vMNTFG KO and MUSTFG KO) mice. vMNTFG KO, generated by crossing TFG floxed with VAChT-Cre, showed deterioration of motor function and muscle atrophy especially in slow-twitch soleus muscle, in line with the predominant Cre expression in slow-twitch fatigue-resistant (S) and fast-twitch fatigue-resistant (FR) motor neurons. Consistently, denervation of the neuromuscular junction (NMJ) was apparent in the soleus, but not in the extensor digitorum longus, muscle. Muscle TFG expressions were significantly downregulated in vMNTFG KO, presumably due to decreased muscle IGF-1 concentrations. However, interestingly, MUSTFG KO mice showed no apparent impairment of muscle movements, though a denervation marker, AChRγ, was elevated and Agrin-induced AChR clustering in C2C12 myotubes was inhibited. Our results clarify that loss of motor neuron TFG is sufficient for the occurrence of NMJ degeneration and muscle atrophy, though lack of muscle TFG may exert an additional effect. Reduced muscle TFG, also observed in aged mice, might be involved in age-related NMJ degeneration, and this issue merits further study.
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Uehira Y., Ueno H., Ebihara E., Uchida T., Nabekura H., Sakoda H., Yonekawa T., Yamaguchi H., Nakazato M.
Journal of Diabetes Investigation 13 ( 6 ) 1011 - 1020 2022年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Diabetes Investigation
Aims/Introduction: The Japanese diabetes treatment guidelines do not specify the first choice of hypoglycemic agents, unlike those of Western countries. Furthermore, the current situation in diabetes treatment is that the choice of hypoglycemic agents is determined by each physician. Therefore, we aimed to determine the current situation in Miyazaki Prefecture, Japan, in this context. For this, we carried out a questionnaire survey among physicians twice regarding the target value of glycated hemoglobin and the choice of hypoglycemic agents in various cases. Materials and Methods: We administered an unsigned questionnaire to physicians in Miyazaki Prefecture, Japan, in July 2016 and March 2020. We divided responses into those of diabetologists and those of non-diabetologists, and analyzed each response. We then compared the results between both years. Results: In total, 18 diabetologists and 142 non-diabetologists responded in 2016, and 21 diabetologists and 134 non-diabetologists responded in 2020. Many diabetologists chose biguanide as the first-line drug for obese type 2 diabetes patients. In addition, the rate of choice of sodium–glucose cotransporter 2 inhibitor (SGLT2i) among physicians almost increased in 2020. Some non-diabetologists, and even a few diabetologists, inappropriately chose SGLT2i and biguanide for patients with severe renal dysfunction. Conclusions: Because SGLT2i became available in 2016 and a few years have passed, both diabetologists and non-diabetologists seemed to refrain from prescribing SGLT2i. However, with the emergence of various lines of firm evidence regarding the use of SGLT2i, physicians started to prescribe it. However, some diabetologists and non-diabetologists chose hypoglycemic agents inadequately; therefore, there is a need for novel and precise information.
DOI： 10.1111/jdi.13750
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Islam M.N., Zhang W., Sakai K., Nakazato Y., Tanida R., Sakoda H., Takei T., Takao T., Nakazato M.
Peptides 151 170763 2022年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Peptides
Ghrelin is a gastric-derived peptide that stimulates feeding, blood glucose elevation, body temperature reduction, and growth hormone (GH) secretion. Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous antagonist of the ghrelin receptor, also called growth hormone secretagogue receptor (GHSR). We studied the effects of LEAP2 administration on feeding, body weight, glycemia, body temperature, and inflammation-related genes in the liver in C57BL/6 J mice and Ghsr-knockout (Ghsr-KO) mice. We found that a single administration of LEAP2 did not abolish fasting-induced food intake in 24-h fasted C57BL/6 J mice or Ghsr-KO mice. Moreover, continuous LEAP2 administration to mice fed ad libitum for 6 days did not affect feeding, body temperature, plasma ghrelin, or blood glucose. By contrast, continuous LEAP2 administration to calorie-restricted C57BL/6 J mice and Ghsr-KO mice induced body weight loss, hypoglycemia, body temperature reduction, and upregulation of Il-6 and Il-1β mRNAs in the liver. Our findings suggest that LEAP2 functions independently of GHSR, implying that LEAP2 affects physiology beyond the ghrelin–GHSR system.
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Fujishiro M., Ishihara H., Ogawa K., Murase T., Nakamura T., Watanabe K., Sakoda H., Ono H., Yamamotoya T., Nakatsu Y., Asano T., Kushiyama A.
Biomedicines 9 ( 8 ) 2021年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biomedicines
To unravel associations between plasma xanthine oxidoreductase (XOR) and diabetic vascular complications, especially distal symmetric polyneuropathy (DSP), we investigated plasma XOR activities using a novel assay. Patients with type 2 diabetes mellitus (T2DM) with available nerve conduction study (NCS) data were analyzed. None were currently taking XOR inhibitors. XOR activity of fasting blood samples was assayed using a stable isotope-labeled substrate and LC-TQMS. JMP Clinical version 5.0. was used for analysis. We analyzed 54 patients. Mean age was 64.7 years, mean body mass index was 26.0 kg/m2, and mean glycated hemoglobin was 9.4%. The loga-rithmically transformed plasma XOR activity (ln-XOR) correlated positively with hypoxanthine, xanthine, visceral fatty area, and liver dysfunction but negatively with HDL cholesterol. ln-XOR correlated negatively with diabetes duration and maximum intima-media thickness. Stepwise multiple regression analysis revealed ln-XOR to be among selected explanatory factors for various NCS parameters. Receiver operating characteristic curves showed the discriminatory power of ln-XOR. Principal component analysis revealed a negative relationship of ln-XOR with F-waves as well as positive relationships of ln-XOR with hepatic steatosis and obesity-related disorders. Taken to-gether, our results show plasma XOR activity to be among potential disease status predictors in T2DM patients. Plasma XOR activity measurements might reliably detect pre-symptomatic DSP.
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Pathological role of pin1 in the development of dss‐induced colitis 査読あり
Matsunaga Y., Hasei S., Yamamotoya T., Honda H., Kushiyama A., Sakoda H., Fujishiro M., Ono H., Ito H., Okabe T., Asano T., Nakatsu Y.
Cells 10 ( 5 ) 2021年5月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cells
Inflammatory bowel diseases (IBDs) are serious disorders of which the etiologies are not, as yet, fully understood. In this study, Peptidyl‐prolyl cis‐trans isomerase NIMA‐interacting 1 (Pin1) protein was shown to be dramatically upregulated in the colons of dextran sodium sulfate (DSS)‐induced ulcerative colitis model mice. Interestingly, Pin1 knockout (KO) mice exhibited significant attenuation of DSS‐induced colitis compared to wild‐type (WT) mice, based on various pa-rameters, including body weight, colon length, microscopic observation of the intestinal mucosa, inflammatory cytokine expression, and cleaved caspase‐3. In addition, a role of Pin1 in inflammation was suggested because the percentage of M1‐type macrophages in the colon was decreased in the Pin1 KO mice while that of M2‐type macrophages was increased. Moreover, Pin1 KO mice showed downregulation of both Il17 and Il23a expression in the colon, both of which have been implicated in the development of colitis. Finally, oral administration of Pin1 inhibitor partially but significantly prevented DSS‐induced colitis in mice, raising the possibility of Pin1 inhibitors serving as therapeutic agents for IBD.
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Prolyl isomerase Pin1 in metabolic reprogramming of cancer cells
Nakatsu Y., Yamamotoya T., Ueda K., Ono H., Inoue M., Matsunaga Y., Kushiyama A., Sakoda H., Fujishiro M., Matsubara A., Asano T.
Cancer Letters 470 106 - 114 2020年2月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（大学・研究所紀要） 出版者・発行元：Cancer Letters
© 2019 Elsevier B.V. Pin1 is one member of a group consisting of three prolyl isomerases. Pin1 interacts with the motif containing phospho-Ser/Thr-Pro of substrates and enhances cis-trans isomerization of peptide bonds, thereby controlling the functions of these substrates. Importantly, the Pin1 expression level is highly upregulated in most cancer cells and correlates with malignant properties, and thereby with poor outcomes. In addition, Pin1 was revealed to promote the functions of multiple oncogenes and to abrogate tumor suppressors. Accordingly, Pin1 is well recognized as a master regulator of malignant processes. Recent studies have shown that Pin1 also binds to a variety of metabolic regulators, such as AMP-activated protein kinase, acetyl CoA carboxylase and pyruvate kinase2, indicating Pin1 to have major impacts on lipid and glucose metabolism in cancer cells. In this review, we focus on the roles of Pin1 in metabolic reprogramming, such as “Warburg effects”, of cancer cells. Our aim is to introduce these important roles of Pin1, as well as to present evidence supporting the possibility of Pin1 inhibition as a novel anti-cancer strategy.
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神経作動性ペプチドの糖代謝や摂食への作用 招待あり
上野浩晶、迫田秀之、中里雅光
Islet Equality 7 16 - 20 2018年
記述言語：日本語 掲載種別：記事・総説・解説・論説等（学術雑誌）
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肥満とグレリン抵抗性. 招待あり
迫田秀之、中里雅光
Pharma Medica 34 55 - 57 2016年5月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（学術雑誌）
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AMP-activated protein kinase (AMPK)
迫田 秀之
生体の科学 66 434 - 435 2015年10月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（学術雑誌） 出版者・発行元：医学書院
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AMP-activated protein kinase（AMPK）?
迫田 秀之
生体の科学 [増大特集]細胞内シグナル操作法, 66 ( 5 ) 434 - 435 2015年9月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（学術雑誌） 出版者・発行元：医学書院
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NMU induces β cell failure by triggering mitochondrial dysfunction and ER stress
Zhang, W, Sakoda H, Miura A, Nakazato M
AMED-CREST International Symposium. Miyazaki. (宮崎)
開催年月日： 2020年1月31日 - 2020年2月1日
記述言語：英語 会議種別：ポスター発表
開催地：宮崎
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NMU induces β cell failure by triggering mitochondrial dysfunction and ER stress.
Zhang, W, Sakoda H, Miura A, Nakazato M.
The IDF (International Diabetes Federation) Congress 2019 (South Korea, Busan)
開催年月日： 2019年12月2日 - 2019年12月6日
記述言語：英語 会議種別：ポスター発表
開催地：South Korea, Busan
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成人期に診断されたKallmann症候群の1例
田中 友梨、山口 秀樹、野田 智穂、海老原 枝美、迫田 秀之、上野 浩晶、米川 忠人、中里 雅光
第29回日本臨床内分泌代謝Update (高知)
開催年月日： 2019年11月29日 - 2019年11月30日
記述言語：日本語 会議種別：ポスター発表
開催地：高知
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グレリンのエネルギー代謝調節における迷走神経求心路の役割
十枝内厚次、岡田只士、ワイズ TMザベッド、三田雄一郎、迫田秀之、中里雅光
第40日本肥満学会 (東京)
開催年月日： 2019年11月2日 - 2019年11月3日
記述言語：日本語 会議種別：口頭発表（一般）
開催地：東京
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1型糖尿病におけるイプラグリフロジンの体重への影響
鍋倉弘樹、上野浩晶、古郷芙未子、田中友梨、野田智穂、海老原枝美、迫田秀之、川野貴久 、水田雅也、栗林忠信、中里雅光
第40回日本肥満学会 (東京)
開催年月日： 2019年11月2日 - 2019年11月3日
記述言語：日本語 会議種別：口頭発表（一般）
開催地：東京
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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ニューロメジンUと関連ペプチドによるデクレチン効果と糖尿病病態との関連の解析
研究課題/領域番号：22K06004 2022年04月 - 2025年03月
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
張 維東、
担当区分：研究分担者
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高脂肪食による神経の炎症から肥満を来す機序の解析
研究課題/領域番号：16K09761 2016年04月 - 2019年03月
科学研究費補助金 基盤研究(C)
担当区分：研究代表者
寄附金・講座・研究部門 【 表示 ／ 非表示 】
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生体制御医学研究講座研究奨学金
寄附者名称：鈴木謙三記念医科学応用研究財団 2020年12月
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生体制御医学研究講座研究奨学金
寄附者名称：日本応用酵素協会 2020年12月
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生体制御医学研究講座研究奨学金
寄附者名称：ﾉﾎﾞﾙﾃﾞｨｽｸﾌｧｰﾏ株式会社 2020年10月
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生体制御医学研究講座研究奨学金
寄附者名称：MSD株式会社 2020年10月
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内科学講座神経呼吸内分泌代謝学分野研究奨学金（成長科学 迫田）
寄附者名称：公益財団法人成長科学協会 2020年04月