University of the Ryukyus · Faculty of Medicine · 教授

Research keywords糖尿病・肥満・diabetes・lifestyle diseases・metabolic syndrome・obesity・メタボリックシンドローム・生活習慣病

Research fieldsMetabolomics・Pathobiological dentistry/Dental radiology・Embryonic/Neonatal medicine・内分泌・代謝学・Endocrinology・内科・Clinical internal medicine・Medicine

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• Adjunct Therapy with Ipragliflozin Exerts Limited Effects on Kidney Protection in Type 1 Diabetes: A Retrospective Study Conducted at 25 Centers in Japan (IPRA-CKD).2025 · 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.
• Extranodal natural killer/T-cell lymphoma with lung involvement in a young adult with suspected mosquito bite hypersensitivity: A case report.2025 · A young adult with suspected pulmonary lymphoma was diagnosed with extranodal natural killer/T-cell lymphoma (ENKTL). The patient had a history of possible mosquito bite hypersensitivity (MBH), suggesting a potential association between MBH and ENKTL. Although ENKTL typically affects middle-aged adults, it has rarely been reported in children with MBH or chronic active Epstein-Barr virus (EBV) disease. This case highlights the challenges of obtaining pathological confirmation from small biopsy samples of pulmonary ENKTL. Detailed history taking and EBV DNA testing may aid in diagnosis, particularly in younger patients.
• Two Cases of Plasmablastic Myeloma Mimicking Plasmablastic Lymphoma With In-Depth Review of Literature.2025 · Kitamura S, Morichika K, Nakachi S, Hanashiro T, Miyagi R, Nakajima T, Nishi Y, Tamaki K, Fukushima T, Masuzaki H
• Unequal distribution of plasma glucagon levels among clustering-based diabetes subtypes: a Japanese cohort.2025 · Abstract Context Hyperglucagonemia contributes to disturbances in glucose metabolism. Data-driven diabetes clustering reflects risk of diabetic complications better than classical classification, type 1 diabetes (T1D) vs. type 2 diabetes (T2D); however, the pathophysiological features have not been clarified. Objective To assess the distribution of plasma glucagon levels among clustering-based diabetes subtypes. Methods A total of 546 Japanese participants with T1D or T2D were categorized into five diabetes subtypes. Plasma glucagon levels were compared across subtypes and factors associated with hyperglucagonemia were evaluated using logistic regression analyses. Results Plasma glucagon levels differed significantly among diabetes subtypes. Among the five subtypes, plasma glucagon levels and the frequency of hyperglucagonemia were highest in the severe insulin-resistant diabetes (SIRD) subtype (45.6%). The SIRD subtype was an independent risk factor for hyperglucagonemia (adjusted odds ratio 2.17, 95%CI 1.03–4.54, P=0.041), even after adjusting for other risk factors, such as body mass index, HbA1c, and metabolic dysfunction-associated steatotic liver disease. Conclusion The distribution of plasma glucagon levels differed among the clustering-based diabetes subtypes. SIRD is a subtype of diabetes with a hyperglucagonemic phenotype. Elucidating the reason for hyperglucagonemia in SIRD may help to clarify the mechanisms underlying the unfavorable clinical phenotype.

• 幼若期ニコチン暴露による成人期肥満の病態モデルマウス樹立と脳ドパミン機構の解明2025 · 基盤研究(C)
• アルコール依存脳とエネルギーセンサーの病態クロストーク2024 · 基盤研究(C)
• 植物油由来機能成分を活用した肥満症に伴う認知機能低下機構の統合的解析と治療応用2023 · 中年期・壮年期の肥満がのちの人生における認知機能低下のリスクを増大させることが注目されており、病態モデルマウスを用いた研究代表者らの一連の研究により、肥満に関連する認知機能低下メカニズムの一部に動物性脂肪（ラード）、アルコール、ニコチンなどに対する依存的行動嗜癖が関与する可能性が明らかになりつつある。 このような背景を踏まえ、本研究では研究代表者らがこれまでに明らかにしてきた『植物油由来機能成分であるγ-オリザノール（米油）とエクストラバージンオリーブ油(EVOO)による動物性脂肪依存の改善効果、消化管免疫・消化管粘膜バリア機能の強化効果』を足掛かりにして植物油由来の食機能成分を活用した肥満症に伴う認知機能低下メカニズムの統合的解析と治療応用に向けた独創的基盤研究を進めている。特にγ-オリザノールにおいては、肥満症に伴う認知機能低下の改善に関わる新規脳メカニズムの解明を目指し、特に脳内アセチルコリン作用バランスに及ぼすγ-オリザノールの新規作用機構の検証を進める。依存的行動嗜癖の持続がのちの認知機能障害を招来するメカニズムが注目を集めており、一方、研究代表者らの先行研究から、後天的にアルコールに対する依存的嗜癖を誘導したモデルマウスに対するγ-オリザノール投与がアセチルコリン分解酵素（AChE）活性阻害を介してアルコール依存状態を効果的に改善することを新規に突き止めたことを踏まえ（アルコール依存症の予防薬及び治療薬並びにアルコール依存症の予防食品及び治療用食品：発明者代表:益崎裕章(特許:第7244002号,登録日：2023年3月13日) 、γ-オリザノールによる認知機能（空間認識能や新規物体認識能）改善にAChEの抑制が関与する可能性を検証する。
• グルコース輸送体標的化イムノトキシンによる成人T細胞白血病の新規治療法開発2022 · 基盤研究(C)

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