Journal of Diabetes Investigation最新文献

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Associations between peripheral blood mitochondrial genomic variants and gestational diabetes mellitus and postpartum abnormal glucose metabolism. 外周血线粒体基因组变异与妊娠期糖尿病和产后糖代谢异常的关系。
IF 3 3区 医学
Journal of Diabetes Investigation Pub Date : 2025-09-12 DOI: 10.1111/jdi.70152
Qing Luo, Jiankun Zhou, Haiyun Wu, Xiayan Qiu, Chunyan Xian, Xiaoting Zhan, Jinbo Liu
{"title":"Associations between peripheral blood mitochondrial genomic variants and gestational diabetes mellitus and postpartum abnormal glucose metabolism.","authors":"Qing Luo, Jiankun Zhou, Haiyun Wu, Xiayan Qiu, Chunyan Xian, Xiaoting Zhan, Jinbo Liu","doi":"10.1111/jdi.70152","DOIUrl":"https://doi.org/10.1111/jdi.70152","url":null,"abstract":"<p><strong>Aims/introduction: </strong>The aim of the study was to investigate the association of single nucleotide polymorphisms, haplogroups, and copy number in the D-loop region of mitochondrial DNA (mtDNA) with the genetic susceptibility to gestational diabetes mellitus (GDM) and postpartum abnormal glucose metabolism (AGM).</p><p><strong>Materials and methods: </strong>This was a case-control study in which peripheral blood samples were collected from 500 GDM patients and 500 normal pregnant women from 14 to 20 weeks of pregnancy. The sequence of the D-loop region of mtDNA was detected by Sanger sequencing, and the copy number of mtDNA was detected by qPCR.</p><p><strong>Results: </strong>Analysis of SNPs in the D-loop region of mtDNA showed that 249d was a risk factor and 309+C and 16193+C were protective factors for GDM. The mtDNA haplogroups R9 and M* were a risk factor and protective factor for GDM, respectively. Compared to the group with normal postpartum glucose tolerance, the haplogroups M7b and N9a were associated with an increased risk of AGM. The whole blood mtDNA copy number was lower in the GDM group than in the control group and was also lower in the postpartum AGM group than in the postpartum normal group. The plasma free mtDNA copy number was higher in the GDM group than in the control group, and higher in the postpartum AGM group than in the normal postpartum group.</p><p><strong>Conclusions: </strong>Mitochondrial genomic variants are associated with the risk of GDM and postpartum AGM, and may provide some etiologic evidence for GDM and postpartum AGM.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Critical methodological concerns regarding the association between metabolic indices and microvascular complications in type 2 diabetes. 代谢指标与2型糖尿病微血管并发症之间关系的关键方法学关注。
IF 3 3区 医学
Journal of Diabetes Investigation Pub Date : 2025-09-08 DOI: 10.1111/jdi.70153
Wenya Han, Mina He
{"title":"Critical methodological concerns regarding the association between metabolic indices and microvascular complications in type 2 diabetes.","authors":"Wenya Han, Mina He","doi":"10.1111/jdi.70153","DOIUrl":"https://doi.org/10.1111/jdi.70153","url":null,"abstract":"","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association between diabetic peripheral neuropathy and lower limb muscle strength in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. 糖尿病周围神经病变与2型糖尿病患者下肢肌力的关系:一项系统综述和荟萃分析
IF 3 3区 医学
Journal of Diabetes Investigation Pub Date : 2025-09-06 DOI: 10.1111/jdi.70123
Yuki Nakashima, Hisashi Maeda, Toshihiro Kawae, Shunsuke Taito, Daisuke Iwaki, Tomoya Hirai, Kiyo Ueda, Yukio Mikami
{"title":"Association between diabetic peripheral neuropathy and lower limb muscle strength in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.","authors":"Yuki Nakashima, Hisashi Maeda, Toshihiro Kawae, Shunsuke Taito, Daisuke Iwaki, Tomoya Hirai, Kiyo Ueda, Yukio Mikami","doi":"10.1111/jdi.70123","DOIUrl":"https://doi.org/10.1111/jdi.70123","url":null,"abstract":"<p><strong>Purpose: </strong>Lower limb muscle strength is often reduced in patients with type 2 diabetes and is associated with a lower quality of life and poorer walking ability. Diabetic peripheral neuropathy (DPN) may contribute to muscle weakness, though evidence is inconsistent. No meta-analysis has specifically examined the effect of DPN on lower limb muscle strength. This study aimed to review the literature and assess whether lower limb muscle strength is reduced in individuals with DPN compared to those without DPN.</p><p><strong>Methods: </strong>MEDLINE, Embase, and CENTRAL were searched for cohort and case-control studies on the association between DPN and lower limb muscle strength in individuals with type 2 diabetes. We pooled mean differences and standard deviations using random effects models. We evaluated the risk of bias in the included studies using the Quality in Prognosis Studies tool and determined the certainty of the evidence using the Grading of Recommendations Assessmet, Development and Evaluation (GRADE) approach.</p><p><strong>Results: </strong>Overall, 25 studies for qualitative synthesis and 23 (2,798 participants) for meta-analysis were selected. The methodological quality demonstrated a moderate risk of bias in 72% of the included studies. There was low-certainty evidence of an association between DPN and lower extremity muscle strength (standardized mean difference -0.46, 95% CI -0.65 to -0.27).</p><p><strong>Conclusions: </strong>Patients with type 2 diabetes and DPN may have lower muscle strength than those without DPN. Moreover, they should be informed of the risk of muscle weakness. Further research is needed to identify factors contributing to lower extremity weakness in DPN and determine which muscle groups are most susceptible.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Beck Depression Inventory-II scores of adults with type 1 diabetes in Japan: Analysis using the Juntendo-Aso Type 1 Diabetes (JAT-1) Cohort. 日本成人1型糖尿病患者的Beck抑郁量表- ii评分:使用Juntendo-Aso 1型糖尿病(JAT-1)队列进行分析
IF 3 3区 医学
Journal of Diabetes Investigation Pub Date : 2025-09-04 DOI: 10.1111/jdi.70151
Fuki Ikeda, Junko Sato, Kenichi Nakajima, Mami Koshibu, Ayako Sato, Katsumi Aso, Yuya Nishida, Hirotaka Watada
{"title":"The Beck Depression Inventory-II scores of adults with type 1 diabetes in Japan: Analysis using the Juntendo-Aso Type 1 Diabetes (JAT-1) Cohort.","authors":"Fuki Ikeda, Junko Sato, Kenichi Nakajima, Mami Koshibu, Ayako Sato, Katsumi Aso, Yuya Nishida, Hirotaka Watada","doi":"10.1111/jdi.70151","DOIUrl":"https://doi.org/10.1111/jdi.70151","url":null,"abstract":"<p><strong>Introduction: </strong>Depressive tendencies associated with difficulty in the treatment of type 1 diabetes (T1D) could hinder appropriate intervention. Factors related to depressive tendencies in Japan remain unclear, though recent advances in medication may have affected them.</p><p><strong>Materials and methods: </strong>Three hundred and fifty-two Japanese patients with T1D registered in the Juntendo-Aso Type 1 (JAT-1) Diabetes Cohort Study were divided into two groups based on depressive tendencies assessed with the Beck Depression Inventory-II score. We compared background characteristics of the patients between the groups and also analyzed additional clinical factors and quality of life scores.</p><p><strong>Results: </strong>The patients with a Beck Depression Inventory-II score ≧14 (35.5%) are classified as having depressive tendencies. Compared to the individuals without depressive characteristics, those with depressive tendencies had significantly higher proportions of females, welfare recipients, and shift workers; a higher proportion of individuals with microvascular complications; higher diastolic pressure; eating out or taking out food more frequently for dinner; lower protein intake; and higher scores in the total score of diabetes-related problem domains and Pittsburgh Sleep Quality Index. Multiple regression analysis revealed that diastolic blood pressure, welfare recipient status, total score of diabetes-related problem domains (PAID), and Pittsburgh Sleep Quality Index were significantly associated factors with BDI-II score, and the PAID score showed the strongest association.</p><p><strong>Conclusions: </strong>This study revealed that diabetes-specific psychological burden, evaluated with the PAID score, is strongly associated with depressive tendencies. Routine use of the PAID could support the strategies to prevent depression in people with type 1 diabetes by identifying those at risk.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical characteristics of Japanese Americans with normal glucose tolerance with 1-h hyperglycemia: A cross-sectional study. 糖耐量正常的日裔美国人1小时高血糖的临床特征:一项横断面研究。
IF 3 3区 医学
Journal of Diabetes Investigation Pub Date : 2025-09-04 DOI: 10.1111/jdi.70148
Natsumi Himeno, Tsuguka Matsuda, Yoshimi Morita, Takaya Kodama, Ryuta Baba, Gentaro Egusa, Gaku Nagano, Noboru Hattori, Haruya Ohno
{"title":"Clinical characteristics of Japanese Americans with normal glucose tolerance with 1-h hyperglycemia: A cross-sectional study.","authors":"Natsumi Himeno, Tsuguka Matsuda, Yoshimi Morita, Takaya Kodama, Ryuta Baba, Gentaro Egusa, Gaku Nagano, Noboru Hattori, Haruya Ohno","doi":"10.1111/jdi.70148","DOIUrl":"https://doi.org/10.1111/jdi.70148","url":null,"abstract":"<p><strong>Aims/introduction: </strong>High 1-h plasma glucose levels have an increased risk of type 2 diabetes. To determine the pathophysiological features in participants with normal glucose tolerance (NGT) with 1-h hyperglycemia (HG), we investigated the variability in the glucagon and insulin secretions after oral glucose loading and nutrient survey.</p><p><strong>Materials and methods: </strong>A 75-g oral glucose tolerance test (OGTT) was performed in Japanese Americans (aged 40-75 years), enrolled in medical surveys conducted in 2015. We recruited only participants with NGT defined as fasting glucose values <110 mg/dL and 2-h glucose levels <140 mg/dL. We evaluated homeostatic model assessment for insulin resistance (HOMA-IR), insulin sensitivity index (MATSUDA-Index), insulin, and glucagon (GCG) secretions during the 75-g OGTT and compared them between 1-h serum glucose values: <155 mg/dL (1-h non-hyperglycemia: NHG, n = 76) and 1-h serum glucose values: ≥155 mg/dL (HG, n = 41). We also conducted a dietary intake survey to determine the association between 1-h serum glucose and nutritional intake in the usual diet.</p><p><strong>Results: </strong>The HG group demonstrated significant insulin resistance compared to the NHG group. Two-h GCG levels were significantly lower in the HG group. Additionally, low vegetable fat intake was significantly associated with 1-h HG after adjusting for sex, age, and body mass index.</p><p><strong>Conclusions: </strong>Insulin resistance is already present in the HG group. Vegetable fat intake may be associated with glucose metabolism regardless of clinical background.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Red cell distribution width (RDW), RDW to albumin ratio (RAR), and long-term mortality in diabetic neuropathy: A NHANES analysis, 1999-2019. 糖尿病神经病变的红细胞分布宽度(RDW)、RDW与白蛋白比(RAR)和长期死亡率:一项NHANES分析,1999-2019。
IF 3 3区 医学
Journal of Diabetes Investigation Pub Date : 2025-09-02 DOI: 10.1111/jdi.70147
Jui-Chu Huang, Pey-Jium Chang, Yi-Lun Chiang
{"title":"Red cell distribution width (RDW), RDW to albumin ratio (RAR), and long-term mortality in diabetic neuropathy: A NHANES analysis, 1999-2019.","authors":"Jui-Chu Huang, Pey-Jium Chang, Yi-Lun Chiang","doi":"10.1111/jdi.70147","DOIUrl":"https://doi.org/10.1111/jdi.70147","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to explore associations between Red cell distribution width (RDW), RDW to albumin ratio (RAR), and long-term all-cause and cardiovascular disease (CVD) mortality in adults with diabetes and DN.</p><p><strong>Methods: </strong>This study included adults aged ≥40 years with DN from the National Health and Nutrition Examination Survey from 1999 to 2004, followed through 2019. Cox proportional hazards models were used to assess associations between RDW, RAR, and all-cause and CVD mortality. Predictive accuracy was determined using area under the curve (AUC) by receiver operating characteristic analyses.</p><p><strong>Results: </strong>Data of a total of 624 participants with DN were analyzed. Each unit increase in RDW significantly increased all-cause mortality by 12% (adjusted hazard ratio (aHR) = 1.12, 95% CI: 1.05-1.20) and CVD mortality by 15% (aHR = 1.15, 95% CI: 1.02-1.31), while each unit increase in RAR increased all-cause mortality by 73% (aHR = 1.73) and CVD mortality by 93% (aHR = 1.93). In the highest versus lowest quartiles, RDW (aHR = 1.89) and RAR (aHR = 2.91) were associated with higher all-cause mortality risk, and even higher risk for CVD mortality (RDW: aHR = 2.86; RAR: aHR = 4.84). The AUC for 5-year predictions was RDW 0.825 and RAR 0.846 for all-cause mortality, and RDW 0.811 and RAR 0.814 for CVD mortality.</p><p><strong>Conclusions: </strong>RDW and RAR are strong predictors of long-term mortality in individuals with DN. RAR demonstrates stronger associations and higher predictive accuracy than RDW, particularly in predicting CVD mortality.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Two decades of diabetes prevention: Sustained benefits, heterogeneous effects, and implications for precision prevention. 二十年的糖尿病预防:持续的益处,异质性的影响,以及对精确预防的影响。
IF 3 3区 医学
Journal of Diabetes Investigation Pub Date : 2025-09-02 DOI: 10.1111/jdi.70150
Seung-Hwan Lee
{"title":"Two decades of diabetes prevention: Sustained benefits, heterogeneous effects, and implications for precision prevention.","authors":"Seung-Hwan Lee","doi":"10.1111/jdi.70150","DOIUrl":"10.1111/jdi.70150","url":null,"abstract":"","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dysregulation of lncRNA OIP5-AS1 participants in the progression of diabetic retinopathy and affects the proliferation in retinal vascular endothelial cell. lncRNA OIP5-AS1的失调参与糖尿病视网膜病变的进展并影响视网膜血管内皮细胞的增殖。
IF 3 3区 医学
Journal of Diabetes Investigation Pub Date : 2025-09-01 DOI: 10.1111/jdi.70091
Ziwen Yin, Jingyun Dong, Yachao Meng, Zhiqiang Yang, Chunhong Zhao, Qiuyun Wu
{"title":"Dysregulation of lncRNA OIP5-AS1 participants in the progression of diabetic retinopathy and affects the proliferation in retinal vascular endothelial cell.","authors":"Ziwen Yin, Jingyun Dong, Yachao Meng, Zhiqiang Yang, Chunhong Zhao, Qiuyun Wu","doi":"10.1111/jdi.70091","DOIUrl":"https://doi.org/10.1111/jdi.70091","url":null,"abstract":"<p><strong>Aims: </strong>This study was to ascertain the clinical performance of OIP5-AS1 in diabetic retinopathy (DR) and its molecular mechanism in the disease progression.</p><p><strong>Materials and methods: </strong>Subjects included 85 healthy controls, 79 patients with type 2 diabetes mellitus (T2DM), and 114 T2DM-DR patients. qRT-PCR was conducted to measure the relative abundances of OIP5-AS1 and miR-181a-5p in the research subjects. Receiver operating characteristic (ROC) and logistic regression analyses were employed for the diagnostic capability and risk factor prediction. Cell activities were assessed using CCK-8 and transwell assays. Luciferase reporter assay was used for the correlation confirmation of OIP5-AS1 and miR-181a-5p. Bioinformatic analysis was applied to predict the potential targets of miR-181a-5p.</p><p><strong>Results: </strong>A significant decrease of OIP5-AS1 was detected in serum from patients with T2MD and T2DM-DR (P < 0.001), exhibiting a high diagnostic value for detecting T2DM (AUC = 0.973) and T2DM-DR patients (AUC = 0.913). OIP5-AS1 was an independent protective indicator for the onset of T2DM-proliferative DR (T2DM-PDR; P = 0.021, OR = 0.306, 95%CI = 0.112-0.837). OIP5-AS1 was markedly reduced in human retinal vascular endothelial cells (HRVECs) with high glucose (HG) (P < 0.001). Overexpression of OIP5-AS1 could significantly suppress the cell growth of HRVECs (P < 0.001). OIP5-AS1 was negatively correlated with miR-181a-5p (r = -0.5327, P < 0.001). Additionally, the impacts caused by OIP5-AS1 on cell events were canceled by transfection of miR-181a-5p mimic (P < 0.001). The possible targets of miR-181a-5p were mined, suggesting mainly enriched in cellular senescence and the MAPK signaling pathway.</p><p><strong>Conclusions: </strong>OIP5-AS1 was downregulated in T2DM-DR patients and regulated cellular functions via targeting miR-181a-5p. It might offer a new therapeutic target for the disease.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NSUN2-mediated m5C methylation modification regulates trophoblast cell proliferation, apoptosis, and autophagy in gestational diabetes mellitus. nsun2介导的m5C甲基化修饰调节妊娠糖尿病滋养细胞增殖、凋亡和自噬。
IF 3 3区 医学
Journal of Diabetes Investigation Pub Date : 2025-08-28 DOI: 10.1111/jdi.70140
Jiujiu Liu, Yingjun Chen, Dapeng Wang, Zhaozhao Li
{"title":"NSUN2-mediated m<sup>5</sup>C methylation modification regulates trophoblast cell proliferation, apoptosis, and autophagy in gestational diabetes mellitus.","authors":"Jiujiu Liu, Yingjun Chen, Dapeng Wang, Zhaozhao Li","doi":"10.1111/jdi.70140","DOIUrl":"https://doi.org/10.1111/jdi.70140","url":null,"abstract":"<p><strong>Introduction: </strong>Gestational diabetes mellitus (GDM) represents one of the most prevalent medical complications during pregnancy. Emerging evidence has implicated NOL1/NOP2/SUN domain (NSUN)2-mediated 5-methylcytosine (m<sup>5</sup>C) methylation modifications in various pathological conditions. This study aimed to investigate the role of m<sup>5</sup>C modification in GDM and to elucidate its underlying mechanisms.</p><p><strong>Materials and methods: </strong>The mRNA expression levels of m<sup>5</sup>C-related RNA methyltransferases were quantified using reverse transcription-quantitative polymerase chain reaction. Cellular viability and proliferation were assessed through Cell Counting Kit-8 and EdU assays. The apoptosis rate was determined by flow cytometry. Western blot was employed to analyze autophagy-related protein expression. The m<sup>5</sup>C modification sites on PTEN-induced putative kinase 1 (PINK1) were identified via dual-luciferase reporter assays. An RNA immunoprecipitation assay was performed to examine NSUN2-PINK1 interactions. Finally, a mouse model was established to further explore the role of NSUN2 in GDM in vivo.</p><p><strong>Results: </strong>Our findings revealed elevated NSUN2 expression in HTR-8/SVneo cells. NSUN2-mediated m<sup>5</sup>C modification suppressed proliferation while enhancing apoptosis, inflammation, and autophagy in high glucose (HG)-stimulated HTR-8/SVneo cells. Mechanistically, NSUN2 upregulated PINK1 expression through an m<sup>5</sup>C-dependent regulation. Pharmacological inhibition of PINK1 reversed these effects, enhancing proliferation while attenuating apoptosis, inflammation, and autophagy under HG conditions. Conversely, PINK1 overexpression exacerbated the observed cellular responses. In vivo, NSUN2 inhibition alleviated inflammation and hyperglycemia in GDM pregnant mice.</p><p><strong>Conclusions: </strong>NSUN2-mediated m<sup>5</sup>C modification promoted GDM progression by upregulating PINK1 expression, leading to impaired trophoblast function. Targeting this NSUN2-m<sup>5</sup>C-PINK1 axis may represent a promising therapeutic strategy for GDM management.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SP1-activated CFL2 promotes high glucose-induced retinal pigment epithelial cell injury and involves the AMPK/mTOR pathway. sp1激活的CFL2促进高糖诱导的视网膜色素上皮细胞损伤,并参与AMPK/mTOR通路。
IF 3 3区 医学
Journal of Diabetes Investigation Pub Date : 2025-08-26 DOI: 10.1111/jdi.70144
Jinan Xiao, Jingni Yu, Mei Ren
{"title":"SP1-activated CFL2 promotes high glucose-induced retinal pigment epithelial cell injury and involves the AMPK/mTOR pathway.","authors":"Jinan Xiao, Jingni Yu, Mei Ren","doi":"10.1111/jdi.70144","DOIUrl":"https://doi.org/10.1111/jdi.70144","url":null,"abstract":"<p><strong>Background: </strong>Cofilin-2 (CFL2) belongs to the cofilin family of actin-binding proteins and plays an important role in the actin homeostasis of muscle cells. CFL2 has been confirmed to regulate diabetic retinopathy (DR) progression. However, the current research is limited and more evidence is needed to reveal its role and mechanism in the DR process.</p><p><strong>Methods: </strong>Retinal pigment epithelial (RPE) cells (ARPE-19) were cultured in high-glucose (HG; 30 mM) conditions to mimic DR cell models. Cell proliferation and apoptosis were examined by CCK8 assay, EdU assay, flow cytometry, and caspase 3 activity detection. Cell oxidative stress, ferroptosis, and inflammation were evaluated by detecting ROS, MDA, SOD, GSH, Fe<sup>2+</sup>, TNF-α, and IL-1β levels. The mRNA and protein levels of CFL2 and special protein 1 (SP1) were tested by qRT-PCR and western blot. CFL2 and SP1 interaction was assessed by ChIP assay and dual-luciferase reporter assay.</p><p><strong>Results: </strong>HG suppressed ARPE-19 cell proliferation, while inducing apoptosis, oxidative stress, ferroptosis, and inflammation. Silencing of CFL2 alleviated HG-induced ARPE-19 cell injury by inhibiting cell apoptosis, oxidative stress, ferroptosis, and inflammation. SP1 could bind to CFL2 promoter regions to increase its expression. SP1 knockdown relieved HG-induced ARPE-19 cell injury via decreasing CFL2 expression. Besides, SP1 knockdown inhibited the activity of the AMPK/mTOR pathway, and CFL2 overexpression could reverse this effect.</p><p><strong>Conclusions: </strong>CFL2, activated by SP1, promoted HG-induced RPE cell injury through regulating the AMPK/mTOR pathway, which might provide a potential target for DR.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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