World Journal of Diabetes最新文献

{"title":"Examining gut microbiota and metabolites to clarify mechanisms of <i>Dimocarpus longan</i> Lour leaf components against type 2 diabetes.","authors":"Piao-Xue Zheng, Chun-Lian Lu, Yan-Li Liang, Yu-Ming Ma, Jia-Wen Peng, Jing-Jing Xie, Jia-Li Wei, Si-Si Chen, Zhi-Dong Ma, Hua Zhu, Jie Liang","doi":"10.4239/wjd.v16.i7.104512","DOIUrl":"10.4239/wjd.v16.i7.104512","url":null,"abstract":"<p><strong>Background: </strong><i>Dimocarpus longan</i> Lour leaf components (DLC) contain key active compounds such as quercetin, kaempferol, and quercitrin. They are effective for managing type 2 diabetes mellitus (T2DM), though the exact mechanism by which DLC acts remains unclear.</p><p><strong>Aim: </strong>To investigate the material basis and mechanism underlying the therapeutic effect of DLC in T2DM.</p><p><strong>Methods: </strong>T2DM was triggered in rats using a high-sugar, high-fat diet alongside 35 mg/kg streptozotocin. The effect of DLC on the intestinal microbiota in T2DM rats was analyzed <i>via</i> 16S rDNA sequencing. Targeted metabolomics was conducted to evaluate the impact of DLC on the levels of nine short-chain fatty acids (SCFAs). Untargeted metabolomics examined DLC-induced alterations in fecal metabolites and associated metabolic pathways. Additionally, Spearman's correlation analysis assessed gut microbiota and fecal metabolite relationships.</p><p><strong>Results: </strong>DLC significantly attenuated pathological weight loss, reduced fasting blood glucose levels, restored blood sugar homeostasis, and ameliorated dyslipidemia in T2DM rats. The 16S rDNA sequencing revealed that DLC enhanced microbial diversity and reversed intestinal dysbiosis. Targeted metabolomics indicated decreased acetic acid and propionic acid levels and increased butyric acid, isobutyric acid, and 2-methylbutyric acid levels after DLC treatment. Untargeted metabolomics revealed 57 metabolites with altered expression associated with amino acid, carbohydrate, purine, and biotin pathways. The Spearman analysis demonstrated significant links between specific gut microbiota taxa and fecal metabolites.</p><p><strong>Conclusion: </strong>DLC may exert hypoglycemic effects by modulating intestinal flora genera, SCFA levels, and fecal metabolites.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 7","pages":"104512"},"PeriodicalIF":4.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692074","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":"Exploring the link: Hemogram-derived markers in type 2 diabetes mellitus and its complications.","authors":"Gulali Aktas","doi":"10.4239/wjd.v16.i7.105233","DOIUrl":"10.4239/wjd.v16.i7.105233","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance, often leading to severe complications. Hemogram markers have attracted great attention from researchers for their established role in inflammatory conditions. In this respect, T2DM and its microvascular complications are characterized by high inflammatory burden. Hence, recent studies in the literature have reported an association between T2DM and hemogram-derived markers. Emerging evidence highlights the utility of hemogram-derived markers, including the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, red cell distribution width, and mean platelet volume, as potential predictors of T2DM onset and progression. These markers, readily available from routine hemogram tests, offer valuable insights into the systemic inflammation and vascular changes associated with T2DM and its complications, such as cardiovascular disease, nephropathy, and retinopathy. This review synthesizes current research on the association between hemogram-derived markers and T2DM, emphasizing their prognostic value in predicting disease severity and complications. We also explore the underlying pathophysiological mechanisms linking these markers to inflammation and metabolic dysfunction. The findings suggest that hemogram-derived markers could serve as cost-effective, non-invasive tools for risk stratification and early intervention in T2DM management. Future research should focus on standardizing reference ranges and validating these markers in diverse populations to enhance their clinical utility.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 7","pages":"105233"},"PeriodicalIF":4.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692076","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":"Progress in the application of mesenchymal stem cells to attenuate apoptosis in diabetic kidney disease.","authors":"Ping Nie, Wei Qin, Wei-Chen Nie, Bing Li","doi":"10.4239/wjd.v16.i6.105711","DOIUrl":"10.4239/wjd.v16.i6.105711","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) has a high incidence and mortality rate and lacks effective preventive and therapeutic methods. Apoptosis is one of the main reasons for the occurrence and development of DKD. Mesenchymal stem cells (MSCs) have shown great promise in tissue regeneration for DKD treatment and have protective effects against DKD, including decreased blood glucose and urinary protein levels and improved renal function. MSCs can directly differentiate into kidney cells or act <i>via</i> paracrine mechanisms to reduce apoptosis in DKD by modulating signaling pathways. MSC-derived extracellular vesicles (MSC-EVs) mitigate apoptosis and DKD-related symptoms by transferring miRNAs to target cells or organs. However, studies on the regulatory mechanisms of MSCs and MSC-EVs in apoptosis in DKD are insufficient. This review comprehensively examines the mechanisms of apoptosis in DKD and research progress regarding the roles of MSCs and MSC-EVs in the disease process.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"105711"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477367","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":"Long-term risk of diabetes following hypertensive disorders of pregnancy: A retrospective cohort study.","authors":"Yu-Hsiang Shih, Chiao-Yu Yang, Chia-Chi Lung","doi":"10.4239/wjd.v16.i6.105080","DOIUrl":"10.4239/wjd.v16.i6.105080","url":null,"abstract":"<p><strong>Background: </strong>The impact of varying degrees of pregnancy-induced hypertension (PIH) on the risk of developing diabetes later in life is currently unknown.</p><p><strong>Aim: </strong>To assess the long-term risks of type 2 diabetes mellitus (T2DM), prediabetes, and mortality that are associated with hypertensive disorders of pregnancy.</p><p><strong>Methods: </strong>This retrospective cohort study used the TriNetX United States Collaborative Network to examine outcomes, especially T2DM, prediabetes and mortality, related to hypertensive disorders of pregnancy in females aged 21-45. Participants had no history of hypertension or diabetes before pregnancy or before 20 weeks of gestation. Propensity score matching was applied to balance covariates such as gestational diabetes, polycystic ovarian syndrome, chronic kidney disease, hyperlipidemia, overweight/obesity, nicotine dependence, alcohol abuse, and healthcare utilization. This ensured comparability between groups and reduced potential confounding in outcome evaluation.</p><p><strong>Results: </strong>This study included 318544 females aged 21-45 with and without PIH. Females with PIH had higher risks of T2DM [hazard ratio (HR): 1.907, 95% confidence interval (CI): 1.821-1.998), prediabetes (HR: 1.610, 95%CI: 1.537-1.687), and mortality (HR: 1.501, 95%CI: 1.361-1.655) over a follow-up of up to 18 years. Incidence rates for T2DM, prediabetes, and mortality were 3.2%, 2.7%, and 0.6%, respectively. Subgroup analyses showed that the presence of gestational hypertension, preeclampsia, and eclampsia increased risks across all outcomes. Persistent hypertension beyond 12 weeks postpartum was linked to more than a 3-fold increase in mortality. Preventative aspirin use during pregnancy did not reduce the risks of T2DM, prediabetes, or mortality among those with PIH.</p><p><strong>Conclusion: </strong>PIH significantly increases the long-term risks of T2DM, prediabetes, and mortality, highlighting the urgent need for improved long-term management strategies to enhance overall health in such individuals.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"105080"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477452","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":"Curcumol targets the FTO/MAFG-AS1 axis to alleviate diabetic retinopathy <i>via</i> epigenetic remodeling and nanodelivery-based microenvironment modulation.","authors":"Cheng Luo, Zhi-Gang Zheng, Mei-Qi Zeng, Hui Xu, Xian-Mei Yu, Da Sun, Dong-Juan He","doi":"10.4239/wjd.v16.i6.107017","DOIUrl":"10.4239/wjd.v16.i6.107017","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is a major microvascular complication of diabetes, with its pathogenesis involving metabolic memory, epigenetic dysregulation, and multi-cellular microenvironmental disorders. This study systematically investigates the mechanism by which curcumol ameliorates DR through regulation of the FTO/MAFG-AS1 epigenetic axis and reveals its therapeutic potential in targeting the retinal microenvironment <i>via</i> a nano-delivery system. Experimental results demonstrate that curcumol activates the demethylase activity of FTO, stabilizing the expression of the long non-coding RNA MAFG-AS1, thereby inhibiting high glucose-induced retinal endothelial cell inflammation, migration, and vascular leakage. Single-cell transcriptomic analysis further uncovered the dual role of FTO in DR: On the one hand, it promotes pathological angiogenesis in endothelial cells, while on the other hand, it exerts protective effects through MAFG-AS1-mediated antioxidative and anti-inflammatory functions. Moreover, this study proposes a multidimensional epigenetic regulatory network based on histone lactylation, N6-methyladenosine modification, and DNA methylation, and verifies that curcumol delays DR progression by coordinately modulating these modifications. To overcome the limitations of conventional therapies, this study innovatively designed a macrophage membrane-coated nano-delivery system, significantly enhancing the retinal targeting and bioavailability of curcumol. Finally, the study advocates a paradigm shift from passive treatment to early prevention, proposing a three-tiered intervention strategy that integrates epigenetic biomarkers with artificial intelligence-based risk assessment. These findings not only elucidate the multi-target regulatory mechanisms of curcumol but also provide a theoretical foundation for the development of precision therapies for DR based on epigenetic remodeling and microenvironmental synergistic intervention.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"107017"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530499","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":"Vitamin D deficiency is associated with apolipoprotein A1 levels in patients with young-onset type 2 diabetes mellitus.","authors":"Ye Hu, Li-Na Shao, Jia Zheng, Xin-Miao Zhang, Ying-Xiang Song, Yu-Bo Xing","doi":"10.4239/wjd.v16.i6.105558","DOIUrl":"10.4239/wjd.v16.i6.105558","url":null,"abstract":"<p><strong>Background: </strong>Young-onset type 2 diabetes mellitus (T2DM) is associated with adverse health outcomes and increased mortality. Vitamin D (VitD) deficiency is likewise linked to various adverse health outcomes and is significantly associated with lipid metabolism in patients with T2DM. However, little is known regarding the mechanisms of interaction between VitD and apolipoprotein A1 (apoA1) in young-onset T2DM.</p><p><strong>Aim: </strong>To evaluate the relationship between VitD and apoA1 levels in patients with young-onset T2DM.</p><p><strong>Methods: </strong>This cross-sectional study was conducted at Zhejiang Provincial People's Hospital between January 2019 and December 2023. A total of 642 patients with T2DM who aged 18-40 years were included and matched with 642 individuals without diabetes (controls) based on age and sex. No specific intervention was applied, and data were collected from medical records and laboratory tests. The relationship between VitD and apoA1 levels was examined using Spearman's correlation and logistic regression models.</p><p><strong>Results: </strong>We found that VitD levels were significantly lower in patients with T2DM compared to controls (15.9 ng/mL <i>vs</i> 17.4 ng/mL, <i>P</i> < 0.001), with a notable positive correlation between VitD deficiency and reduced apoA1 levels. Multifactor logistic regression analysis identified that severe VitD deficiency was an independent risk factor for apoA1 in young-onset T2DM patients (odds ratio = 3.43, 95% confidence interval: 1.16-10.20, <i>β</i> = 1.23, <i>P</i> = 0.026).</p><p><strong>Conclusion: </strong>Our findings reveal an association between VitD and apoA1 in young-onset T2DM, suggesting that VitD may play a crucial role in metabolic regulation and cardiovascular risk management.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"105558"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477371","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":"Association between anemia and the risk of diabetic foot ulcer: A meta-analysis.","authors":"Shi-Shuai Lin, Cun-Ren Chen, Wei-Cheng Xu, Jia Fu, Jia-Qin Xu, Zun-Hong Liang","doi":"10.4239/wjd.v16.i6.105155","DOIUrl":"10.4239/wjd.v16.i6.105155","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcers (DFUs) are a major complication of diabetes mellitus, and anemia is commonly observed in diabetic patients. However, the relationship between anemia and the risk of developing DFUs remains unclear.</p><p><strong>Aim: </strong>To investigate the relationship between anemia and the risk of DFUs in diabetic patients through a meta-analysis.</p><p><strong>Methods: </strong>A systematic search was conducted across PubMed, Embase, and Web of Science databases to identify studies that reported the co-occurrence of anemia and DFUs in diabetic patients. The primary outcome was an association between anemia and DFU risk, expressed as odds ratios (ORs). Secondary outcomes included the risk of DFU per 1-g/dL decrease in hemoglobin and the difference in hemoglobin levels between patients with and without DFU. Statistical analyses were performed using random-effects models to account for heterogeneity.</p><p><strong>Results: </strong>Sixteen studies involving 170,949 diabetic patients were included in the analysis. The results indicated a significant association between anemia and an increased risk of DFUs (eight studies, <i>n</i> = 166173, OR: 2.72, 95%CI: 1.73-4.25, <i>P</i> < 0.001; <i>I</i> ² = 93%). Subgroup analyses supported consistent findings across various patient characteristics, analytic models, and study quality scores (<i>P</i> for subgroup differences, all > 0.05). Additionally, each 1-g/dL decrease in hemoglobin was associated with an excess risk of DFUs (four studies, <i>n</i> = 2543, OR: 1.65, 95%CI: 1.21-2.27, <i>P</i> = 0.002; <i>I</i> ² = 68%). Furthermore, diabetic patients with DFUs exhibited significantly lower hemoglobin levels compared to those without DFUs (nine studies, <i>n</i> = 3986, mean difference: -2.13 g/dL, 95%CI: -2.58 to -1.68, <i>P</i> < 0.001; <i>I²</i> = 90%).</p><p><strong>Conclusion: </strong>Anemia can be associated with an increased risk of DFUs in diabetic patients. Monitoring and managing anemia in diabetic population may help mitigate the risk of DFUs, emphasizing the need for early interventions. Further research is required to investigate the underlying mechanisms and potential therapeutic strategies.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"105155"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477431","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":"Identification and validation of serum amino acids as diagnostic biomarkers for diabetic peripheral neuropathy.","authors":"Wei-Sheng Xu, Huan Xing, Qing-Qing Wang, Hui Qi, Jian-Tao He, Tong Jin, Yan-Peng Kan, Shi-Yu Sun, Ji-Ying Wang, Fu-Qing Lin","doi":"10.4239/wjd.v16.i6.105592","DOIUrl":"10.4239/wjd.v16.i6.105592","url":null,"abstract":"<p><strong>Background: </strong>Diabetic peripheral neuropathy (DPN) is the most prevalent complication of type 2 diabetes mellitus (T2DM). Due to a lack of specific biomarkers, the early diagnosis of this disorder is limited.</p><p><strong>Aim: </strong>To identify and validate serum amino acids that could discriminate T2DM patients with DPN from those without DPN.</p><p><strong>Methods: </strong>T2DM patients with DPN, T2DM patients without DPN, and healthy controls were recruited for this study. The participants comprised two nonoverlapping cohorts: A training cohort (DPN = 84 participants, T2DM = 82 participants, normal = 50 participants) and a validation cohort (DPN = 112 participants, T2DM = 93 participants, normal = 58 participants). A prediction model of the ability of serum amino acids to distinguish DPN from T2DM was established using a logistic regression model, and area under the curve (AUC) analysis was used to evaluate the diagnostic ability of the model. In addition, the serum amino acid levels of 13 DPN patients were also detected before treatment and after 3 months of treatment.</p><p><strong>Results: </strong>A clinical detection method for the diagnosis of DPN based on a biomarker panel of three serum amino acids and diabetes duration was developed. The diagnostic model demonstrated AUC values of 0.805 (95%CI: 0.739-0.871) and 0.810 (95%CI: 0.750-0.870) in the training and verification cohorts, respectively. In the identification of T2DM patients and normal controls, the AUC values were 0.891 (95%CI: 0.836-0.945) and 0.883 (95%CI: 0.832-0.934) in the training and validation cohorts, respectively. Arginine and tyrosine levels were increased after treatment, whereas aspartic acid levels were decreased after treatment.</p><p><strong>Conclusion: </strong>This study successfully identified and validated the metabolomic significance of arginine, tyrosine, and glutamic acid as potential biomarkers for diagnosing DPN. These findings are particularly valuable, as they establish a foundational step toward developing the first routine laboratory test for DPN. Moreover, the diagnostic model that was constructed in this study effectively distinguishes DPN patients from those with T2DM without neuropathy, thereby potentially facilitating early diagnosis and intervention.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"105592"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477446","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":"Immune biomarkers as early indicators of renal damage in type 1 diabetic children: A step toward translational medicine.","authors":"Jian-Wen Fan, Su-Yi Xu, Jun Wu, Yong-Wei Yu","doi":"10.4239/wjd.v16.i6.106884","DOIUrl":"10.4239/wjd.v16.i6.106884","url":null,"abstract":"<p><p>An article recently published in the <i>World Journal of Diabetes</i>, provides valuable insights into using immune biomarkers to identify renal damage in pediatric patients with newly diagnosed type 1 diabetes (T1D). Although these findings are promising, clinical translation of these immune markers into routine diagnostics and preventive care remains challenging. In this letter, we propose building on the authors' work by exploring the integration of immune biomarkers into a more comprehensive dynamic risk stratification model for early renal injury. Combining immune system indicators with metabolic and genetic factors could enhance the predictive accuracy and support more personalized interventions. Longitudinal studies are needed to evaluate temporal changes in immune biomarkers and their association with long-term renal outcomes in children with T1Ds. Immunomodulatory therapies targeting early immune dysfunction can prevent or slow the progression of diabetic nephropathy. By incorporating these aspects, we hope to translate immune biomarkers from research into practical clinical tools, ultimately improving patient outcomes and reducing the burden of kidney-related complications in pediatric diabetes.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"106884"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477447","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":"Mechanism of trypsin-mediated differentiation of pancreatic progenitor cells into functional islet-like clusters.","authors":"Ling Gao, Jia-Shuang Lai, Han Chen, Li-Xia Qian, Wan-Jin Hong, Liang-Cheng Li","doi":"10.4239/wjd.v16.i6.102727","DOIUrl":"10.4239/wjd.v16.i6.102727","url":null,"abstract":"<p><strong>Background: </strong>Endogenous regeneration of pancreatic islet β-cells is a path to cure both type 1 and advanced type 2 diabetes. Pancreatic cancer cell line-1 (PANC-1), a human pancreatic islet progenitor cell line, can be induced by trypsin to differentiate into insulin-secreting islet-like aggregates (ILAs). However, the underlying mechanism has not been explored.</p><p><strong>Aim: </strong>To explore the mechanism and signaling pathway of trypsin-induced differentiation of islet progenitor cells into insulin-secreting cells.</p><p><strong>Methods: </strong>PANC-1 cells were induced by trypsin to form ILAs and differentiate into insulin-secreting cells. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 knockout and small interfering RNA knockdown techniques were used to investigate membrane proteins and downstream signaling pathways involved in the process.</p><p><strong>Results: </strong>The extracellular domain of membrane receptor E-cadherin hydrolyzed by trypsin induced the aggregation of PANC-1 cells and stimulated E-cadherin-recruited casein kinase-1γ3, which specifically phosphorylated the Ser655/Thr658 site of α-catenin in the cadherin-catenin complex, participating in the process of PANC-1 differentiation and affecting the maturation of differentiated ILAs.</p><p><strong>Conclusion: </strong>The current study reveals the mechanism by which trypsin promotes PANC-1 cell differentiation into islet-like cells, providing a novel approach for endogenous islet β-cell regeneration.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"102727"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477365","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}