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Faculty of Medicine College Hospital Department of Endocrinology, Metabolism and Diabetes Medicine |
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UENO Hiroaki
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Research Areas 【 display / non-display 】
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Life Science / Metabolism and endocrinology
Papers 【 display / non-display 】
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Ueno H., Mizuta M., Shiiya T., Tsuchimochi W., Noma K., Nakashima N., Fujihara M., Nakazato M.
Diabetes Care 37 ( 7 ) 2024 - 2027 2014.7
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Diabetes Care
OBJECTIVE: This study aimed to assess the efficacy and safety of our newly developed nasal glucagon-like peptide-1 (GLP-1) compound and injector. RESEARCH DESIGN AND METHODS: Twenty-six patients with type 2 diabetes were enrolled in this double-blind placebo-controlled study. The nasal compound containing 1.2 mg of human GLP-1 (7-36) amide or placebo was administered immediately before every meal for 2 weeks. RESULTS: The plasma peak concentration of active GLP-1 was 47.2 pmol/L, and its Tmax was 8.1 min. The early phase of insulin and glucagon secretion were recovered and suppressed, respectively, in the GLP-1 group. Glycoalbumin levels became significantly lower and 1,5-anhydroglucitol levels significantly higher after GLP-1 administration. No marked adverse events were observed after using nasal GLP-1. CONCLUSIONS: The newly developed nasal GLP-1 compound may be a potential treatment for type 2 diabetes. The long-term application of the drug should be evaluated in future trials. © 2014 by the American Diabetes Association.
DOI： 10.2337/dc13-0690
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Tahira Yuki, Shide Kotaro, Kameda Takuro, Uchida Taisuke, Kamiunten Ayako, Akizuki Keiichi, Kubuki Yoko, Karasawa Masayoshi, Ikeda Ryoma, Matsumoto Kengo, Bai Jie, Terashima Minoru, Kato Koji, Uto Tomofumi, Fukaya Tomohiro, Mitoma Shuya, Sato Katsuaki, Uehira Yudai, Ueno Hiroaki, Sashida Goro, Yamaguchi Hideki, Shimoda Kazuya
Blood Neoplasia 2 ( 3 ) 100087 2025.8
Language：English Publishing type：Research paper (scientific journal)
Interferon-α (IFN-α) exhibits antiviral and antiproliferative effects on normal and neoplastic cells. Intracellular signaling of IFN-α is mediated by tyrosine kinase 2 (TYK2) and janus kinase 1 (JAK1), followed by signal transducers and activators of transcription (STATs). TYK2 is redundant for the antiviral effect of IFN-α; however, the requirements for antiproliferative effects are unknown. We assessed the role of TYK2 in the effects of IFN-α in myeloproliferative neoplasm (MPN) model mice. Jak2V617F transgenic mice develop MPNs resembling human primary myelofibrosis, and ropeginterferon-α-2b ameliorated their features. However, these IFN-α effects were absent in Jak2V617F;Tyk2−/− mice. In mixed wild-type (WT)/Jak2V617F chimeric mice, IFN-α treatment induces Jak2V617F hematopoietic stem cells (HSCs) to enter the cell cycle and skew their differentiation into the megakaryocyte lineage, decreasing the number of Jak2V617F HSCs. The effects of IFN-α on Jak2V617F HSCs were not observed in mixed WT/Jak2V617F;Tyk2−/− mice, indicating that TYK2 is essential for the effects of IFN-α on both Jak2V617F progenitors and HSCs. The mechanism of IFN-α in Jak2V617F HSCs and progenitors differed: genes regulating the cell cycle were enriched in IFN-α–stimulated Jak2V617F HSCs, but not in Jak2V617F progenitors; genes regulating antiproliferation were enriched in IFN-α–stimulated Jak2V617F progenitors but not in Jak2V617F HSCs. The major IFN-α signaling molecule activated by JAKs is STAT1, which is essential for the antiviral effect. Most effects of IFN-α on Jak2V617F cells were preserved in Jak2V617F;Stat1−/− mice but to a moderate degree compared with Jak2V617F mice. Our study reveals essential roles of TYK2 for the preferential suppressive effect of IFN-α on Jak2V617F progenitors and HSCs.
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上野 浩晶
Biomedicines 13 ( 6 ) 1287 2025.5
Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI
Background/Objectives: While sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated additional non-glycemic benefits for renal protection in individuals with type 2 diabetes, less evidence is available for those with type 1 diabetes (T1D). To determine whether the adjunctive use of the SGLT2 inhibitor ipragliflozin confers kidney protection in individuals with T1D, we retrospectively analyzed data from a real-world cohort examined at 25 centers in Japan. Methods: We enrolled 359 subjects aged 20–74 years with T1D (IPRA group: 159 ipragliflozin users; control [CTRL] group: 200 non-users). The primary outcome was changes in the estimated glomerular filtration rate (eGFR) from baseline to 24 months after the initiation of ipragliflozin. The secondary outcomes were all other changes, including the urinary albumin–creatinine ratio (UACR) and urinary protein–creatinine ratio (UPCR). Results: The IPRA group’s eGFR decline slopes were 0.79 mL/min/1.73 m2/year milder than the CTRL group’s after propensity score matching, but this difference was not significant. The subjects complicated by chronic kidney disease (CKD) defined as UACR ≥ 30 mg/g and/or UPCR ≥ 0.5 g/g and/or eGFR < 60 mL/min/1.73 m2 showed changes in UPCR (g/g) from baseline to 24 months that were significantly lower in the IPRA group (−0.27 ± 1.63) versus the CTRL group (0.18 ± 0.36) (p = 0.016). No significant increase in adverse events (including severe hypoglycemia and hospitalization due to ketosis/ketoacidosis or cardiovascular diseases) was observed in the IPRA group. Conclusions: Adjunctive treatment with ipragliflozin exerted potential renal benefits by decreasing proteinuria in T1D subjects with CKD. Further investigations are required to determine whether its additional benefits exceed the increased risk of ketoacidosis.
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GLP-1受容体作動薬による視床下部を介する体重減少効果 Invited
上野浩晶
脳神経内科 102 344 - 350 2025.3
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal)
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Impaired humoral immunity following COVID-19 vaccination in HTLV-1 carriers Reviewed
Kameda T., Utsunomiya A., Otsuka N., Kubuki Y., Uchida T., Shide K., Kamiunten A., Nakano N., Tokunaga M., Miyazono T., Ito Y., Yonekura K., Kawakita T., Akizuki K., Tahira Y., Karasawa M., Hidaka T., Konagata A., Taniguchi N., Nagatomo Y., Kogo F., Shimizu K., Ueno H., Ishizaki J., Takahashi N., Ikei Y., Hidaka M., Yamaguchi H., Shimoda K.
BMC Infectious Diseases 24 ( 1 ) 96 2024.12
Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Infectious Diseases
Background: Whether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown. Methods: To investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors. Results: We analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers. Conclusions: The humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.
Books 【 display / non-display 】
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食欲調節機構
上野浩晶（ Role： Sole author）
肥満症診療ガイドライン2022, 日本肥満学会 編、ライフサイエンス出版 2022.12
Language：Japanese Book type：Scholarly book
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DPP-4阻害薬
上野浩晶、中里雅光（ Role： Joint author）
南江堂 2021.10
Language：Japanese Book type：Scholarly book
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脳内炎症と肥満
上野浩晶、中里雅光（ Role： Joint author）
羊土社 2021.3
Language：Japanese Book type：Scholarly book
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SGLT2阻害薬の体重減少作用について
上野浩晶、中里雅光（ Role： Joint author）
中外医学社 2020.4
Responsible for pages：51-57 Language：Japanese Book type：Scholarly book
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カンナビノイド系：内科学書 改訂第8版
上野浩晶、中里雅光（ Role： Joint author）
中山書店 2020
Responsible for pages：20200000 Language：Japanese Book type：Scholarly book
MISC 【 display / non-display 】
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肥満症治療薬の成功率を上げるために Invited
上野浩晶
Medical Practice 41 310 - 310 2024
Authorship：Lead author Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)
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食事療法の一工夫 Invited
上野浩晶
はまゆう ( 131 ) 3 - 4 2022.4
Authorship：Lead author Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (other)
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高度肥満に対する内科的治療が奏功している例とリバウンド例 Invited
上野浩晶、中里雅光
Medical Practice 38 ( 7 ) 1096 - 1101 2021.7
Authorship：Lead author Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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Liver-expressed antimicrobial peptide2(LEAP-2)の成長ホルモン分泌における生理的役割および病態との関連
迫田秀之, 酒井克也, 鍋倉弘樹, 谷田亮太, 上野浩晶, 山口秀樹
成長科学協会研究年報 ( 44 ) 2021
Language：Japanese Publishing type：Rapid communication, short report, research note, etc. (scientific journal)
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高PRL性無月経を来した維持透析1型糖尿病へのドパミン製剤の治療経験
山口 秀樹, 松下 隆司, 内田 泰介, 田中 友梨, 古郷 芙未子, 鍋倉 弘樹, 上平 雄大, 迫田 秀之, 上野 浩晶, 中里 雅光
糖尿病 63 ( 4 ) 246 - 246 2020.4
Language：Japanese Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：(一社)日本糖尿病学会
Presentations 【 display / non-display 】
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グレリン受容体の内因性アンタゴニストliver-expressed antimicrobial peptide 2(LEAP2)の産生・分泌の制御因子解析
鍋倉弘樹, ヌルール イスラム, 上野浩晶, 張 維東, 迫田秀之, 中里雅光
第67回日本糖尿病学会年次学術集会
Event date： 2025.5.17 - 2025.5.19
Presentation type：Oral presentation (general)
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GIP/GLP-1受容体作動薬 Invited
上野浩晶
第62回日本糖尿病学会九州地方会
Event date： 2024.10.25 - 2025.10.26
Presentation type：Public lecture, seminar, tutorial, course, or other speech
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急性発症１型糖尿病に微小変化型ネフローゼ症候群を同時期に発症した１例
2古郷芙未子、内田泰介、鍋倉弘樹、別府拓海、菊池幸、積島愛加理、与那嶺真一、上平雄大、上野浩晶、山口秀樹、下田和哉
第62回日本糖尿病学会九州地方会
Event date： 2024.10.25 - 2024.10.26
Presentation type：Oral presentation (general)
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実臨床での２型糖尿病に対するチルゼパチドとセマグルチドの効果比較
上野浩晶、与那嶺真一、古郷芙美子、上平雄大、鍋倉弘樹、内田泰介、菊池幸、別府拓海、山口秀樹、下田和哉
第31回西日本肥満研究会
Event date： 2024.7.13 - 2024.7.14
Presentation type：Oral presentation (general)
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DASC-8カテゴリーはインスリン自己注射手技の正確性と関連し手技指導の有効性を予測する
内田泰介、上野浩晶、積島愛加理、積島宏昂、小永田綾香、古郷芙未子、鍋倉弘樹、田中友梨、山口秀樹、下田和哉
第66回老年医学会学術集会
Event date： 2024.6.13 - 2024.6.15
Presentation type：Oral presentation (general)
Awards 【 display / non-display 】
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日本糖尿病学会九州支部賞
2015.11 日本糖尿病学会九州支部
上野浩晶
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
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博慈会オープンセサミ賞
2014.2 博慈会
上野浩晶
Award type：Award from publisher, newspaper, foundation, etc. Country：Japan
Grant-in-Aid for Scientific Research 【 display / non-display 】
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グレリン併用運動療法の多面的抗生活習慣病作用に関する研究
Grant number：23500782 2011.04 - 2014.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
糖尿病を初めとする生活習慣病の治療に関して、グレリンの持つ成長ホルモン(GH)非依存性のグレリン特異的作用、および運動時に惹起されるＧＨ分泌亢進の増強を介した糖・脂質代謝改善と体組成の改善作用（除脂肪体重の増加と脂肪重量の減少）を検証する。また、グレリンが糖尿病性神経障害、腎症および動脈硬化性病変に対する改善作用を持ち、多面的な抗生活習慣病薬となり得ることを検討する。
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新規ペプチド オベスタチンおよびグレリンの肥満に対する病態生理学的意義の検討
Grant number：19591061 2007.04 - 2009.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
胃から産生・分泌される新規ペプチドであるオベスタチンおよびグレリンの肥満に対する病態生理学的意義の検討を行う