Journal of Diabetes Investigation最新文献

{"title":"Letter to the editor in response to the association between COVID-19 and incident gestational diabetes (GDM): A population-based case-control study of the National Health Insurance Research Database in Taiwan","authors":"Komal Fatima,&nbsp;Ammara Shaikh,&nbsp;Adnan Memon","doi":"10.1111/jdi.70254","DOIUrl":"10.1111/jdi.70254","url":null,"abstract":"<p>Dear Editor,</p><p>We recently read with great interest the article by Lin <i>et al</i>. titled, “The association between COVID-19 and incident gestational diabetes (GDM),”<span>¹</span> which analyzed data from Taiwan's National Health Insurance Research Database (NHIRD). While the authors conducted a large population-based study using robust national data, certain methodological elements may limit the interpretation of the reported lack of association between COVID-19 infection and incident GDM.</p><p>First, misclassification of COVID-19 exposure represents a major concern. Infection status was identified solely through documented test results and healthcare records; consequently, asymptomatic or mildly symptomatic pregnant women who did not seek testing or medical care were regarded as unexposed. Such non-differential exposure misclassification would be expected to bias the observed associations toward the null. Causal inference frameworks highlight how the incomplete capture of exposure can significantly attenuate effect estimates when classification is imperfect<span>²</span>.</p><p>Second, key metabolic risk factors for GDM were not available in the NHIRD, including prepregnancy BMI, gestational weight gain, smoking status, and family history of diabetes. Although morbid obesity was included, it represents only extreme cases and is an inadequate substitute for continuous BMI. Observational studies using routine healthcare databases often lack these variables, making residual confounding likely<span>³</span>.</p><p>Third, the exclusion of pregnancies ending before 24 weeks could introduce selection bias. Since early pregnancy loss occurs among individuals infected with COVID-19, restricting the cohort to pregnancies proceeding 24 weeks may underrepresent those with early complications. While a recent meta-analysis showed a non-statistically significant trend toward higher odds of miscarriage (OR ≈ 1.44, 95% CI 0.96–2.18), another systematic review found no evidence of an increased risk (OR ≈ 1.10, 95% CI 0.81–1.48) but noted persistent low to moderate certainty of evidence. These potential selection effects remain an important consideration in case-control designs that require ongoing pregnancy for case ascertainment<span>⁴</span>.</p><p>In conclusion, although the study offers important insights in the medical field, addressing the limitations, such as exposure misclassification and the absence of granular metabolic data, could enhance the robustness of the findings. We appreciate the author's contribution to this significant topic.</p><p>The authors declare no conflict of interest.</p><p>Approval of the research protocol: None.</p><p>Informed consent: None.</p><p>Registry and registration number: None.</p><p>Animal studies: None.</p><p>Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.</p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re: Commentary on “Impact of diabetes mellitus and grip strength on postoperative outcomes in older patients undergoing cancer surgery: A single-center retrospective cohort study”","authors":"Tian Ruan","doi":"10.1111/jdi.70258","DOIUrl":"10.1111/jdi.70258","url":null,"abstract":"<p>Dear Editor-in-Chief,</p><p>We read with great interest the study by Fujimoto <i>et al</i>. [<span>1</span>], published in the <i>Journal of Diabetes Investigation</i> (2025, DOI: https://doi.org/10.1111/jdi.70224), examining the impact of diabetes mellitus and grip strength on postoperative outcomes in older patients undergoing gastrointestinal cancer surgery. This work makes a valuable contribution to geriatric oncology by emphasizing that reduced physical function, particularly weakened grip strength, emerges as a more significant independent predictor of adverse postoperative outcomes than current diabetes mellitus status in elderly surgical patients.</p><p>We commend the authors' finding that current diabetes mellitus status does not independently predict postoperative survival when physical function is accounted for, a clinically reassuring result that challenges the traditional assumption of diabetes as a major independent surgical risk factor. This observation underscores the paramount importance of comprehensive geriatric assessment and targeted optimization of physical function in all older patients undergoing cancer surgery, regardless of glycemic status.</p><p>This work was supported by the Yunnan Provincial Department of Education Science Research Fund (Grant No. 2024J2133) and the Yunnan Medical Health College University-level Research Project Fund (Grant No. 2024Y010).</p><p>This manuscript is a commentary on a previously published article and does not involve any original research with human participants or animals. Therefore, ethical approval was not required for this work.</p><p>Approval of the research protocol: Not applicable. This manuscript is a commentary on a previously published article and does not involve any original research with human participants.</p><p>Informed consent: Not applicable. No human participants were involved in this work.</p><p>Registry and the registration no. of the study/trial: Not applicable. This is a letter to the editor/commentary, not a clinical trial or registered study.</p><p>Animal studies: Not applicable. No animal studies were conducted.</p><p>Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.</p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"703-704"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of anagliptin/metformin combination tablets evaluated by non-inferiority between pre- and post-serum lactic acid levels in Japanese patients with type 2 diabetes and moderate renal impairment (AMELIO STUDY)","authors":"Hiroshi Kajio,&nbsp;Ryotaro Bouchi,&nbsp;Mitsuhisa Komatsu,&nbsp;Masanori Yamazaki,&nbsp;Daisuke Takarabe,&nbsp;Masahide Okamoto,&nbsp;Takahisa Tanaka,&nbsp;Toru Kitazawa,&nbsp;Hisayuki Katsuyama,&nbsp;Yasumichi Mori,&nbsp;Mitsuhiko Noda","doi":"10.1111/jdi.70253","DOIUrl":"10.1111/jdi.70253","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>To investigate the safety of anagliptin/metformin combination tablets by evaluation of lactic acid levels in Japanese patients with type 2 diabetes and moderate renal impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>The participants of type 2 diabetes with creatinine-based eGFR (eGFRcr) of ≥45 and &lt;60 (mL/min/1.73 m²) (Group G3a) received anagliptin/metformin combination LD tablets (anagliptin: 100 mg, metformin hydrochloride: 250 mg/tablet) twice a day for 4 weeks. After 4 weeks, they received anagliptin/metformin combination HD tablets (anagliptin: 100 mg, metformin hydrochloride: 500 mg/tablet) twice daily until after 16 weeks. The participants (Group G3b) with baseline eGFRcr ≥30 and &lt;45 (mL/min/1.73 m²) received anagliptin/metformin combination LD tablets twice daily for 16 weeks. The serum lactic acid levels were examined at weeks 4, 8, and 16 after receiving anagliptin/metformin combination tablets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The change in serum lactic acid levels from baseline to 16 weeks was −0.09 [−0.28, 0.10] mmol/L (mean [95% confidence intervals]), not exceeding the pre-specified non-inferiority margin (0.7 mmol/L). No significant differences occurred in the change in serum lactic acid levels during all observation periods. Serum lactic acid levels exceeded 2.5 mmol/L in four participants (10.5%) and 5.0 mmol/L in one participant (2.6%) during the observation period. No participant had a plasma metformin exceeding 2.5 μg/mL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates that the fixed-dose combination of anagliptin and metformin can be used safely in patients with type 2 diabetes complicated by moderate renal dysfunction. The advantage of this fixed-dose combination is also considered to be very large.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"636-648"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of extracellular and membrane potentials in imeglimin-treated islets","authors":"Asuka Tsurumoto,&nbsp;Ryota Inoue,&nbsp;Esther Ong Yajima,&nbsp;Meng Zou,&nbsp;Junyu Luo,&nbsp;Takahiro Tsuno,&nbsp;Emi Ishida,&nbsp;Kohichi Matsunaga,&nbsp;Jun Shirakawa","doi":"10.1111/jdi.70265","DOIUrl":"10.1111/jdi.70265","url":null,"abstract":"<p>Glucose-stimulated insulin secretion (GSIS) in β cells depends critically on membrane depolarization–induced Ca²⁺ influx. Accordingly, the electrophysiological assessment of intact islets, where β cells act as functional syncytia, is essential for evaluating insulin secretory dynamics. Imeglimin, an oral agent used in treating type 2 diabetes, increases insulin secretion; however, its effects on β-cell electroactivity remain unclear. Here, we investigated extracellular and membrane potentials in imeglimin-treated mouse islets using microelectrode array (MEA) recordings and a plasma membrane potential indicator (PMPI). Imeglimin augmented first-phase insulin release and significantly increased the fraction of the plateau phase (FOPP), an MEA-derived parameter reflecting secretory competence, under 11.1 mM glucose. Consistent with these findings, the increase in PMPI fluorescence demonstrated enhanced membrane depolarization in response to imeglimin at high-glucose concentrations. These findings indicate that imeglimin potentiates β-cell electroactivity, thereby facilitating GSIS at the islet level.</p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"561-566"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calebin A mitigates oxidative stress and inflammation in diabetic nephropathy via Nrf2/HO-1 and NF-κB signaling pathways","authors":"Reyhane Ghayour Vatanparast,&nbsp;Mahdieh Aliyari,&nbsp;Mahla Palizkaran Yazdi,&nbsp;Soodeh Alidadi,&nbsp;Mohammad Reza Sokhanvar,&nbsp;Sercan Karav,&nbsp;Prashant Kesharwani,&nbsp;Hossein Hosseini,&nbsp;Amirhossein Sahebkar","doi":"10.1111/jdi.70267","DOIUrl":"10.1111/jdi.70267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetic nephropathy (DN) is a common and serious microvascular complication of diabetes mellitus, primarily driven by persistent hyperglycemia-induced oxidative stress and chronic inflammation. Calebin A, a naturally occurring noncurcuminoid compound, has shown promising antioxidant and anti-inflammatory effects in various disease models. This study aimed to evaluate the nephroprotective effects and underlying mechanisms of calebin A in an experimental model of DN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>DN was induced in C57BL/6 mice using streptozotocin (STZ). Diabetic mice were treated with calebin A, curcumin, or metformin for 6 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment with calebin A resulted in significant improvements in glycemic control, renal function, oxidative stress, inflammation, fibrosis, and renal histopathological alterations. Calebin A reduced oxidative stress and inflammation by activating the Nrf2 pathway and downregulating the NF-κB signaling pathway. Histological analyses supported these findings by demonstrating marked attenuation of STZ-induced renal damage following calebin A administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results highlight the multitargeted nephroprotective effects of calebin A in DN. Further long-term and clinically oriented studies are warranted to validate these effects in chronic disease settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"588-598"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic differences in glycemic markers for detecting impaired glucose tolerance in Black African and White European men in the United Kingdom: The SOUL-DEEP cross-sectional study","authors":"Louise M. Goff,&nbsp;Gráinne Whelehan,&nbsp;Toyosi Bello,&nbsp;Anneka Ghafar,&nbsp;Meera Ladwa,&nbsp;Danielle H. Bodicoat,&nbsp;Melinda Stanners,&nbsp;Stephanie A. Amiel","doi":"10.1111/jdi.70251","DOIUrl":"10.1111/jdi.70251","url":null,"abstract":"<p>Ethnic differences in type 2 diabetes risk highlight the need for accurate detection of impaired glucose tolerance (IGT) across all ethnic groups. This study assessed the sensitivity and specificity of HbA1c, fasting plasma glucose (FPG), and 1-h plasma glucose for identifying IGT in 66 Black African (BA) and 77 White European (WE) men. Participants underwent a 75 g oral glucose tolerance test, and diagnostic performance was evaluated using ROC analyses. One-hour glucose showed the highest sensitivity (BA 77.8%, WE 94.1%) and AUC (0.78), whereas FPG 6.1–6.9 mmol/L had the poorest sensitivity (≤7.4%) and lowest AUC (0.49). HbA1c demonstrated ethnic variation: WHO criteria (6.0–6.4%) were more sensitive but less specific in BA than WE men; ADA criteria (5.7–6.4%) showed reduced specificity in BA men. Optimal cut-points differed by ethnicity for all markers. Findings suggest HbA1c and FPG may inadequately detect IGT, while 1-h glucose offers superior diagnostic performance.</p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"622-626"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of switching from MiniMed™ 770G to 780G on continuous glucose monitoring metrics and DTR-QOL scores: An observational study of Japanese people with type 1 diabetes mellitus","authors":"Eri Takagi,&nbsp;Junko Sato,&nbsp;Tatsuhiro Ayame,&nbsp;Shohei Fujikawa,&nbsp;Ryoki Mori,&nbsp;Haruna Yasuda,&nbsp;Azusa Ozaki,&nbsp;Haruki Nagashima,&nbsp;Mami Koshibu,&nbsp;Yuya Nishida,&nbsp;Fuki Ikeda,&nbsp;Hirotaka Watada","doi":"10.1111/jdi.70257","DOIUrl":"10.1111/jdi.70257","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We sought to compare the MiniMed™ 770G to the 780G insulin pump for glycemic control and quality of life in Japanese adults with T1D over a one-year period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-six adults with T1D who switched from the MiniMed™ 770G to the 780G system were analyzed over 48 weeks using continuous glucose monitoring data, retrospectively. The percentages of time within the target glucose range (70–180 mg/dL), time above 180 mg/dL, and time below 70 mg/dL were compared before and after switching. Quality of life (QOL) scores were also evaluated in 39 patients using a validated questionnaire, prospectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After switching to the MiniMed™ 780G, the time within the target glucose range significantly increased from 71.6 ± 12.4% to 76.1 ± 10.2% (<i>P</i> &lt; 0.01), while the time above 180 mg/dL decreased from 25.2 ± 13.4% to 21.0 ± 11.0% (<i>P</i> &lt; 0.01). The time below 70 mg/dL did not differ significantly overall, but nocturnal hypoglycemia decreased from 4.9% to 2.7% (<i>P</i> = 0.02). Glycated hemoglobin improved from 7.2 ± 0.8% to 7.0 ± 0.7% (<i>P</i> &lt; 0.01). Although the total QOL score did not change significantly, the subscales reflecting anxiety and treatment satisfaction improved significantly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Switching from the MiniMed™ 770G to the 780G system in Japanese adults with T1D improved both glycemic control and treatment-related QOL, supporting the clinical usefulness of the 780G in real-world clinical practice. This study provides the first one-year real-world evidence of MiniMed™ 780G use in Japan.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"681-688"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression profile of circular RNAs in type 2 diabetes mellitus patients with retinopathy","authors":"Wencheng An,&nbsp;Bingyan Wang,&nbsp;Fang Chen,&nbsp;Bo An,&nbsp;Shujing Zhou,&nbsp;Lin Jiang,&nbsp;Zhijun Cui,&nbsp;Xiaohong Ou,&nbsp;Wei Huang,&nbsp;Huixian Yan","doi":"10.1111/jdi.70241","DOIUrl":"10.1111/jdi.70241","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Diabetic retinopathy (DR) is a prevalent chronic complication of type 2 diabetes mellitus (T2DM), contributing significantly to vision impairment. Circular RNAs (circRNAs) have emerged as key regulators in the pathogenesis of DR. This study aimed to investigate the differential expression profiles and potential functions of circRNAs in patients with DR compared to those without DR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In this single-center, prospective study, serum samples from 20 T2DM patients with DR and 20 without DR were analyzed using the Arraystar Human circRNA Expression Profile V2.0 microarray. An additional cohort of 40 patients (20 DR and 20 without DR) was used to validate selected circRNAs via quantitative reverse transcription PCR (qRT-PCR). Enriched signaling pathways were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. CircRNA–miRNA–mRNA interaction networks were constructed using bioinformatics tools.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 376 circRNAs were differentially expressed, including 169 upregulated and 207 downregulated circRNAs. qRT-PCR validation confirmed five downregulated circRNAs and three upregulated circRNAs, which were selected for competing endogenous RNA analysis. The circRNA–miRNA–mRNA network analysis revealed that hsa_circRNA_407262 (also known as circRNA LOC389906) may act as a miRNA sponge regulating key signaling pathways, including wingless/integrated, gonadotropin-releasing hormone, tumor necrosis factor, and rat sarcoma pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identified five downregulated and three upregulated circRNAs associated with DR. Among them, hsa_circRNA_407262 may play a crucial role in the pathological process of DR and holds potential as a candidate biomarker for early diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"663-671"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous GIP signaling is indispensable for DPP-4 inhibitor-mediated metabolic control in mice","authors":"Saki Kubota-Okamoto,&nbsp;Sodai Kubota,&nbsp;Hiromi Tsuchida,&nbsp;Yanyan Liu,&nbsp;Seiya Banno,&nbsp;Toshinori Imaizumi,&nbsp;Taro Fujisawa,&nbsp;Yoshihiro Takahashi,&nbsp;Takehiro Kato,&nbsp;Yukio Horikawa,&nbsp;Katsumi Iizuka,&nbsp;Takaaki Murakami,&nbsp;Yuuka Fujiwara,&nbsp;Hitoshi Kuwata,&nbsp;Yuji Yamazaki,&nbsp;Yutaka Seino,&nbsp;Shin Tsunekawa,&nbsp;Daisuke Yabe","doi":"10.1111/jdi.70252","DOIUrl":"10.1111/jdi.70252","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Dipeptidyl peptidase-4 (DPP-4) inhibitors enhance circulating levels of biologically intact incretins, yet the relative contribution of glucose-dependent insulinotropic polypeptide (GIP) to their metabolic effects remains incompletely understood. While glucagon-like peptide-1 (GLP-1) has long been emphasized in incretin biology, emerging evidence suggests important physiological roles for GIP. This study investigated whether endogenous GIP signaling is indispensable for the glucose-lowering and anti-obesity effects of DPP-4 inhibition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Male <i>Gipr</i>^+/+ and <i>Gipr</i>^{<i>−/−</i>} mice were treated with anagliptin or linagliptin under normal diet or high-fat diet (HFD) conditions. Glucose tolerance, insulin secretion, incretin levels, body weight, and adiposity were assessed. To confirm GLP-1 pathway integrity, dulaglutide was administered to a subset of animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DPP-4 inhibition significantly improved glucose tolerance and attenuated body-weight gain in HFD-fed <i>Gipr</i>^<i>+/+</i> mice, without affecting food intake. These effects were abolished in <i>Gipr</i>^{<i>−/−</i>} mice, despite similar elevations in circulating biologically intact GIP and GLP-1. Under normal diet, DPP-4 inhibitors enhanced early-phase insulin secretion and lowered glucose levels in <i>Gipr</i>^<i>+/+</i> mice, but not in <i>Gipr</i>^{<i>−/−</i>} mice. Importantly, dulaglutide restored glucose-lowering effects in <i>Gipr</i>^{<i>−/−</i>} mice, confirming preserved GLP-1 receptor function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Endogenous GIP signaling is essential for both glucose-lowering and anti-obesity actions of DPP-4 inhibitors in mice. GLP-1 elevation alone is insufficient to compensate for GIP receptor deficiency. These findings refined the mechanistic understanding of DPP-4 inhibitors, highlighted the physiological importance of GIP, and suggested context-dependent metabolic actions of incretins.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"567-575"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-155-5p promotes endothelial–mesenchymal transition and oxidative stress in diabetic retinopathy","authors":"Wenwen Dou,&nbsp;Changbo Fu,&nbsp;Lei Jin,&nbsp;Ting Li,&nbsp;Mingxing Li","doi":"10.1111/jdi.70209","DOIUrl":"10.1111/jdi.70209","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>MicroRNA (miRNA) has been confirmed to be related to gene expression regulation and disease progression. However, the role of miR-155-5p in diabetic retinopathy remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>The retinal microvascular endothelial cells (RMECs) were treated with high glucose, and then the changes of miR-155-5p, endothelial cell markers (CD31 and VE-cadherin), mesenchymal cell markers (SM22α and α-SMA), and VEGF were detected by RT-qPCR. The apoptotic markers (Bax, Bcl-2, cleaved caspase-3) were detected by Western blotting. Additionally, miRNA inhibitors or small interfering RNA were used to regulate the levels of miR-155-5p and DDAH1. Subsequently, the changes in endothelial–mesenchymal transition markers, oxidative stress markers, and apoptotic proteins were observed. The regulatory relationship between miR-155-5p and DDAH1 was investigated using dual-luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After culturing RMECs with high glucose, the level of miR-155-5p increased. After the miR-155-5p level was reduced, the levels of CD31 and VE-cadherin increased, while the levels of SM22α, α-SMA and VEGF decreased. Additionally, the downregulation of miR-155-5p significantly inhibited the increase in ROS and Malondialdehyde (MDA) levels as well as cell apoptosis. DDAH1 is the downstream target of miR-155-5p. The downregulation of DDAH1 significantly weakened the inhibitory effects of miR-155-5p downregulation on endothelial–mesenchymal transition, oxidative stress, and cell apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In diabetic retinopathy, miR-155-5p affects the endothelial–mesenchymal transition process and oxidative stress levels of RMECs through DDAH1 and reduces cell apoptosis induced by high glucose.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"599-607"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}