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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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cAMP-GEFII is a direct target of cAMP in regulated exocytosis Reviewed
Ozaki N., Shibasaki T., Kashima Y., Miki T., Takahashi K., Ueno H., Sunaga Y., Yano H., Matsuura Y., Iwanaga T., Takai Y., Seino S.
Nature Cell Biology 2 ( 11 ) 805 - 811 2000.11
Language：English Publishing type：Research paper (scientific journal) Publisher：Nature Cell Biology
Although cAMP is well known to regulate exocytosis in many secretory cells, its direct target in the exocytotic machinery is not known. Here we show that cAMP-GEFII, a cAMP sensor, binds to Rim (Rab3-interacting molecule, Rab3 being a small G protein) and to a new isoform, Rim2, both of which are putative regulators of fusion of vesicles to the plasma membrane. We also show that cAMP-GEFII, through its interaction with Rim2, mediates cAMP-induced, Ca2+-dependent secretion that is not blocked by an inhibitor of cAMP-dependent protein kinase (PKA). Accordingly, cAMP-GEFII is a direct target of cAMP in regulated exocytosis and is responsible for cAMP-dependent, PKA-independent exocytosis.
DOI： 10.1038/35041046
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Fibrocytes drive JAK2V617F-mutated myelofibrosis: pitavastatin reverses marrow fibrosis and anemia. Reviewed
Uchida T, Shide K, Kameda T, Ozono Y, Kubuki Y, Tahira Y, Kamiunten A, Marutsuka K, Akizuki K, Karasawa M, Uehira Y, Ueno H, Yamaguchi H, Shimoda K
Blood 2026.7
Language：English Publishing type：Research paper (scientific journal)
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Tanaka Y., Ueno H., Sawada H., Konagata A., Uchida T., Uehira Y., Kogo F., Sekishima A., Moritake H., Yamaguchi H., Shimoda K.
Frontiers in Endocrinology 17 1868458 2026
Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers in Endocrinology
Background – Acquired lipodystrophy is a rare disorder characterized by adipose tissue loss or dysfunction and is frequently associated with severe insulin resistance and metabolic complications. Metabolic complications of lipodystrophy have occasionally been reported after hematopoietic stem cell transplantation (HSCT), but their clinical features and optimal treatment strategies remain poorly defined. Tirzepatide, a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has recently emerged as a novel therapy for type 2 diabetes. Case presentation – We report a 37-year-old woman who underwent allogeneic HSCT at 12 years of age for relapsed acute lymphoblastic leukemia after a conditioning regimen including total body irradiation (TBI), high-dose cytarabine, and melphalan. She subsequently developed diabetes mellitus and fatty liver disease at 17 years of age. Although no apparent fat loss was initially recognized, lipodystrophy was clinically suspected based on severe insulin resistance and metabolic abnormalities disproportionate to her body habitus. Computed tomography at 37 years of age revealed region-specific fat loss extending from the lower back to the gluteal region. Glycemic control remained inadequate despite high-dose insulin therapy and sequential treatment with several GLP-1 receptor agonists. After initiation of tirzepatide, glycemic control improved dramatically, allowing complete discontinuation of insulin therapy. Body weight decreased modestly and hepatic steatosis improved. The high-molecular-weight (HMW)/total adiponectin ratio after treatment was elevated (64.0%), suggesting possible improvement in adipocyte secretory function. Conclusion – This case highlights acquired partial lipodystrophy developing after HSCT, supported by region-specific fat loss and characteristic metabolic abnormalities, and demonstrates a marked therapeutic response to tirzepatide. Dual incretin receptor agonism may represent a promising therapeutic strategy for severe insulin resistance associated with adipose tissue dysfunction, potentially through both weight-dependent and weight-independent mechanisms.
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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.
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