World Journal of Diabetes最新文献

{"title":"Mechanism of the epidermal growth factor receptor in promoting endothelial cell dysfunction in gestational diabetes mellitus.","authors":"Dan Tang, Cheng-Fen Wang, Jue Wang, Xiao-Tao Jing, Jing Ma","doi":"10.4239/wjd.v16.i6.105173","DOIUrl":"10.4239/wjd.v16.i6.105173","url":null,"abstract":"<p><strong>Background: </strong>Epidermal growth factor receptor (EGFR) is a transmembrane protein that is differentially expressed in gestational diabetes mellitus (GDM). Endothelial dysfunction is a hallmark of GDM and plays a key role in its pathogenesis. EGFR is associated with endothelial dysfunction in the context of various diseases. However, the exact mechanism by which EGFR causes endothelial dysfunction in GDM is unknown, particularly its regulation at the transcriptional and protein levels.</p><p><strong>Aim: </strong>To explore the molecular mechanism by which EGFR influences endothelial cell dysfunction in GDM at the transcriptional and protein levels.</p><p><strong>Methods: </strong>Quantitative real-time polymerase chain reaction was used to detect the expression of EGFR and <i>H19</i>. Western blotting was used to detect the expression of endothelial cell dysfunction markers. A cell counting kit 8 assay was used to assess cell viability, flow cytometry was used to assess apoptosis, scratch and Transwell assays were used to assess cell migration, and a tube formation assay was used to assess cell vascular formation. Hematoxylin-eosin staining was used to observe histopathological changes in the placentas of the mice.</p><p><strong>Results: </strong>In this study, EGFR was upregulated in clinical samples, GDM animal models and GDM cell models, and the knockdown of EGFR could mitigate the effect of streptozotocin (STZ) and high glucose (HG); promoted the proliferation, migration and vascularization of human umbilical vein endothelial cells (HUVECs); inhibited cell apoptosis and the expression of endothelial cell dysfunction markers (vascular cell adhesion molecule-1, tumor necrosis factor-α, vascular endothelial growth factor-A, and intercellular cell adhesion molecule-1); and alleviated the process of GDM <i>in vivo</i>. Mechanistically, <i>EIF4A3</i> binding to long noncoding RNA <i>H19</i> increased the stability of EGFR messenger RNA, thereby promoting HG-induced HUVECs dysfunction or STZ-induced endothelial cell dysfunction in GDM mice. In addition, <i>ERRFI1</i> also regulated the expression of EGFR, and <i>ERRFI1</i> inhibited EGFR activity by binding to EGFR, thereby inhibiting HG-induced HUVECs dysfunction.</p><p><strong>Conclusion: </strong>Our study revealed that EGFR can accelerate the development of GDM by promoting endothelial cell dysfunction.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"105173"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477364","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":"Pig bile powder maintains blood glucose homeostasis by promoting glucagon-like peptide-1 secretion <i>via</i> inhibiting farnesoid X receptor.","authors":"Yi-Min Sun, Jun-Liang Kuang, Hui-Heng Zhang, Xi-Xi Xia, Jie-Yi Wang, Dan Zheng, Ke-Jun Zhou, Ya-Jun Tang, Ai-Hua Zhao, Wei Jia, Guo-Xiang Xie, Xiao-Jiao Zheng","doi":"10.4239/wjd.v16.i6.103616","DOIUrl":"10.4239/wjd.v16.i6.103616","url":null,"abstract":"<p><strong>Background: </strong>Traditional Chinese medicine offers many valuable remedies for maintaining blood glucose homeostasis in patients with type 2 diabetes mellitus. Bile powder (BP) is a powdered form of bile derived from pigs. It has been used historically in various medicinal applications. Currently, the therapeutic potential of BP in regulating glucose homeostasis remains unclear. Bile acids (BAs) are increasingly recognized for their role in glucose metabolism particularly through the modulation of glucagon-like peptide-1 (GLP-1).</p><p><strong>Aim: </strong>To investigate BP effects on glucose homeostasis and elucidate its mechanistic role through GLP-1 and farnesoid X receptor (FXR) signaling.</p><p><strong>Methods: </strong>A diabetic mouse model was established using a high-fat diet and streptozotocin administration. Mice were treated with BP at doses of 25, 50, or 75 mg/kg/day for 45 days. Glucose homeostasis was assessed <i>via</i> the oral glucose tolerance test and insulin tolerance test. Serum GLP-1 levels were measured by enzyme-linked immunosorbent assay. A GLP-1 receptor antagonist and an FXR agonist were used to clarify the underlying mechanisms. <i>In vitro</i> STC-1 murine enteroendocrine cells were treated with a BP-mimicking BA mixture to assess GLP-1 secretion and proglucagon gene expression.</p><p><strong>Results: </strong>BP treatment significantly improved glucose homeostasis in the diabetic mouse model as indicated by lower blood glucose (<i>P</i> < 0.05) and improved insulin sensitivity. BP enhanced GLP-1 secretion (<i>P</i> < 0.05), which was an effect abolished by the GLP-1 receptor antagonist. This observation confirmed its dependence on GLP-1 signaling. In STC-1 cells, BP-derived BA mixtures stimulated GLP-1 secretion and upregulated proglucagon expression (<i>P</i> < 0.05). Mechanistically, BP inhibited FXR signaling as evidenced by the reversal of its effects upon fexaramine administration. In addition, long-term BP treatment suppressed FXR signaling, resulting in elevated GLP-1 levels and preventing glucose dysregulation.</p><p><strong>Conclusion: </strong>BP improved glucose homeostasis by promoting GLP-1 secretion <i>via</i> FXR inhibition, highlighting its potential as a therapeutic strategy for metabolic disorders.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"103616"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477366","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":"Trends and predictors of diabetes mellitus after living kidney transplantation: A retrospective study.","authors":"Amil Huseynov, Sevim Nuran Kuşlu Çicek","doi":"10.4239/wjd.v16.i6.105069","DOIUrl":"10.4239/wjd.v16.i6.105069","url":null,"abstract":"<p><strong>Background: </strong>Post-transplant diabetes mellitus (PTDM) is a common metabolic adverse event following kidney transplantation, negatively impacting graft function and patient outcomes.</p><p><strong>Aim: </strong>To evaluate the frequency of PTDM and to determine predictive factors in living donor individuals who have undergone kidney transplantation.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 1200 living donor kidney transplant recipients treated between 2016 and 2023. Demographic, clinical, and treatment data were collected, and PTDM was identified based on American Diabetes Association criteria. Statistical analysis included logistic regression analysis to determine independent predictors of PTDM.</p><p><strong>Results: </strong>PTDM was diagnosed in 162 patients (13.5%). Risk factors included older age [odds ratio (OR) 1.03, <i>P</i> = 0.03], increased body mass index (OR 1.08, <i>P</i> = 0.02), a genetic predisposition to diabetes (OR 1.95, <i>P</i> = 0.001), and corticosteroid use (OR 1.30, <i>P</i> = 0.04). Most PTDM cases (61.7%) occurred during the initial 6 months after transplant. Tacrolimus-based regimens were more commonly associated with PTDM compared to other protocols. Renal function at 12 months was comparable between PTDM and non-PTDM groups.</p><p><strong>Conclusion: </strong>PTDM remains a significant concern in kidney transplantation, particularly among patients with modifiable risk factors. Optimizing immunosuppressive regimens, implementing early metabolic monitoring, and addressing modifiable risks such as BMI may help reduce PTDM incidence. Additional research is required to evaluate extended-term results and refine preventive strategies.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"105069"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477370","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":"Ras homolog enriched in brain 1 regulates β cell mass and β cell function <i>via</i> mTORC1/AMPK/Notch1 pathways.","authors":"Yan Yang, Wan-Juan Song, Jing-Jing Zhang","doi":"10.4239/wjd.v16.i6.104973","DOIUrl":"10.4239/wjd.v16.i6.104973","url":null,"abstract":"<p><strong>Background: </strong>The identification of key regulators of β cell mass and function is crucial in developing effective therapeutic interventions for diabetes. Ras homolog enriched in brain 1 (Rheb1), an upstream binding protein of mTOR, is a potential therapeutic target for β cell in diabetes, while the underlying mechanisms remains unknown.</p><p><strong>Aim: </strong>To assess the effect and potential mechanism of Rheb1 on β cell mass and function.</p><p><strong>Methods: </strong>Islets samples were collected from mouse and human donors. Min6 transformed cell line and mouse models including pancreatic or β-cell specific knockout of Rheb1mice were established. Rapamycin (an mTORC1 inhibitor) and AICAR (an AMPK activator) was used to investigate mTORC1 or AMPK signaling in β cells. The effect of Rheb1 on β cell function <i>via</i> mTORC1, AMPK or other pathways were assessed using western blotting and immunofluorescence, <i>etc.</i></p><p><strong>Results: </strong>In this study, we demonstrate that Rheb1 is highly expressed in islets from young human donors (below the age of 18) compared to adults. Furthermore, our findings reveal that Rheb1 facilitates β-cell proliferation through both mTORC1 and AMPK signaling pathways, rather than solely relying on mTORC1. Specifically, we observed that either AICAR or rapamycin alone could partially inhibit Rheb1-induced β cell proliferation, while the combination of AICAR and rapamycin fully inhibits Rheb1-induced β cell proliferation in Min6 transformed cell line and mouse islets. In addition, our study highlights the role of Rheb1 in maintaining β cell identity through activation of mTORC1 and Notch1 signaling pathways. Moreover, we also found that Rheb1 could positively regulate HNF4α in β cells, which is a significant transcription factor for β-cell development and differentiation.</p><p><strong>Conclusion: </strong>Overall, our findings reveal that Rheb1 regulates β cell proliferation and identity and β-cell development related significant marker, providing a promising novel therapeutic target for diabetes.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"104973"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477368","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":"Associations of nontraditional lipoprotein ratios with future cardiovascular events in patients with type 2 diabetes mellitus.","authors":"Si-Min Deng, Xin-Qun Hu, Xiang-Yu Zhang","doi":"10.4239/wjd.v16.i6.104120","DOIUrl":"10.4239/wjd.v16.i6.104120","url":null,"abstract":"<p><strong>Background: </strong>Patients with type 2 diabetes mellitus (T2DM) face a heightened risk of future cardiovascular events. It is therefore important to stratify these patients according to their future cardiovascular event risk to allow early intervention and improve prognosis. Recent proposals have indicated that nontraditional lipoprotein ratios may be superior predictors of cardiovascular events compared to traditional lipid parameters. However, further evidence is required for widespread clinical application.</p><p><strong>Aim: </strong>To elucidate the associations of nontraditional lipoprotein ratios with future cardiovascular events in patients with T2DM.</p><p><strong>Methods: </strong>This study performed post-hoc analysis of data obtained during a clinical trial involving 10182 participants. To ascertain the correlations between nontraditional lipoprotein ratios and future cardiovascular events, including major adverse cardiovascular events (MACEs) and congestive heart failure (CHF). We employed univariable and multivariable-adjusted Cox proportional hazards regression models. Potential dose-response relationships and threshold values were explored by conducting restricted cubic spline analyses and two-piecewise linear regression models. Possible relevant interactions influencing independent relationships were tested using subgroup and interaction analyses.</p><p><strong>Results: </strong>After adjustment for confounding factors, all nontraditional lipoprotein ratios studied were strongly associated with MACE risk in patients with T2DM. In comparison with patients in the lowest quartile, the hazard ratios (95% confidence intervals) of those in the highest quartile were 1.50 (1.29-1.73), 1.51 (1.30-1.74), 1.50 (1.29-1.73), and 1.30 (1.12-1.50) for total cholesterol/high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol/HDL-C, non-HDL-C/HDL-C, and remnant cholesterol/HDL-C, respectively. Similar findings were noted for CHF. Dose-response relationships between nontraditional lipoprotein ratios and MACE were observed, with threshold values of 7.29, 6.29, and 2.15 for total cholesterol/HDL-C, non-HDL-C/HDL-C, and remnant cholesterol/HDL-C, respectively. However, no notable dose-response relationships were detected between nontraditional lipoprotein ratios and CHF.</p><p><strong>Conclusion: </strong>Elevated nontraditional lipoprotein ratios may independently predict the risk of MACE and CHF in patients with T2DM.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"104120"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477433","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":"Does low physical activity cause cognitive decline in elderly type 2 diabetes patients: A propensity score matching analysis.","authors":"Yi-Xin Ma, Jing Li, Si-Cong Si, Huan Zhao, Jia Liu, Long-Feng Lv, Kai Yang, Wei Yang","doi":"10.4239/wjd.v16.i6.105496","DOIUrl":"10.4239/wjd.v16.i6.105496","url":null,"abstract":"<p><strong>Background: </strong>The relationship between low physical activity and cognitive impairment in type 2 diabetes mellitus (T2DM) patients remains unclear.</p><p><strong>Aim: </strong>To explore this association and identify risk factors for cognitive impairment in elderly T2DM patients.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 245 elderly T2DM patients treated at Xuanwu Hospital, Beijing, in 2023. Patients were categorized into low physical activity (<i>n</i> = 126) and non-low physical activity (<i>n</i> = 119) groups. After propensity score matching (PSM) of 100 pairs, univariate and binary logistic regression analyses identified risk factors for cognitive impairment. A predictive model was constructed and evaluated using receiver operating characteristic curve analysis.</p><p><strong>Results: </strong>Before PSM, the percentage of cognitive impairment was higher in the low physical activity group (<i>P</i> < 0.05), but after PSM, this difference was not significant (<i>P</i> > 0.05). Additionally, on regression analyses after PSM, age, occupation type, history of stroke, malnutrition, and frailty remained independent factors associated with cognitive impairment, while low physical activity did not. The constructed risk prediction model for cognitive impairment in elderly T2DM patients exhibited an area under the curve of 0.77.</p><p><strong>Conclusion: </strong>Low physical activity was not associated with cognitive impairment in our study population. Some results differed before and after PSM analysis, indicating that PSM supports objective assessment of risk factors by controlling for selection bias and confounding factors related to population characteristics. The constructed cognitive risk model provides insight for the development of a clinical tool for early prevention of cognitive impairment in elderly T2DM patients.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"105496"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477438","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":"Glycated hemoglobin is not enough: The role of glycemia risk index for glycemic control assessment in type 1 diabetes.","authors":"Bin-Bin He, Zi-Zhu Liu, Ruo-Yao Xu, Li Fan, Rui Guo, Chao Deng, Yu-Ting Xie, Zhi-Guang Zhou, Xia Li","doi":"10.4239/wjd.v16.i6.104024","DOIUrl":"10.4239/wjd.v16.i6.104024","url":null,"abstract":"<p><strong>Background: </strong>Glycated hemoglobin (HbA1c), the gold standard for assessing glycemic control, has limited ability to reflect the risks of hypoglycemia and glycemic variability, raising great concerns, especially in patients with type 1 diabetes (T1D). The glycemia risk index (GRI), a composite metric derived from continuous glucose monitoring (CGM), has emerged as a potential solution by systematically integrating both hypoglycemia and hyperglycemia risks into a single interpretable score.</p><p><strong>Aim: </strong>To evaluate whether the GRI addresses HbA1c limitations.</p><p><strong>Methods: </strong>We analyzed 328 patients with T1D using 681 CGM and clinical data points. Linear mixed-effects models were used to address the relationship between the GRI and HbA1c within repeated-measures data. Correlation and cluster analyses were used to assess the comprehensive GRI reflection of seven key ambulatory glucose profile parameters.</p><p><strong>Results: </strong>The GRI exhibited linear correlations with HbA1c (<i>r</i> = 0.53), time in range (<i>r</i> = -0.90), time above range (<i>r</i> = 0.63), time below range (TBR) (<i>r</i> = 0.37), and coefficient of variation (CV) (<i>r</i> = 0.71). It correlated strongly with TBR and CV than HbA1c. The association between HbA1c levels and GRI was influenced by TBR and CV. At a given HbA1c, each 1% increase in TBR or CV raised GRI by 1.87 [95% confidence interval (CI): 1.72-2.01] and 1.94 (95%CI: 1.80-2.10), respectively (<i>P</i> < 0.001). Clustering of the CGM data identified four subgroups: Moderate-risk glycemic fluctuations, high-risk hypoglycemia, optimal glycemic control, and high-risk hyperglycemia. The GRI and its components for hypoglycemia and hyperglycemia could distinguish between these subgroups.</p><p><strong>Conclusion: </strong>The GRI offers a comprehensive view of glycemic control in T1D. Combining HbA1c with the GRI enables accurate assessment for managing glycemic control in patients with T1D.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"104024"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477445","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":"Lipid metabolism of <i>Acetobacter pasteurianus</i> and its main components with hypoglycemic effects.","authors":"Wen-Yan Xu, Wen-Ting Zhou, Jia-Zi Luo, Yu-Ying Jiang, Kai Zhang, Shu-Yan Zhang, Ping-Sheng Liu, Hong-Yu Wei, Yan-Qiang Huang","doi":"10.4239/wjd.v16.i6.103370","DOIUrl":"10.4239/wjd.v16.i6.103370","url":null,"abstract":"<p><strong>Background: </strong>Probiotic <i>Acetobacter pasteurianus</i> is used to treat diabetes, but its specific hypoglycemic substances and mechanisms remain unclear.</p><p><strong>Aim: </strong>To investigate the components for lipid metabolism of <i>A. pasteurianus</i> and its hypoglycemic effects, providing a basis for its broader application.</p><p><strong>Methods: </strong>The lipid metabolism of <i>A. pasteurianus</i> under different growth conditions was analyzed using lipidomics. Neutral lipid staining in <i>A. pasteurianus</i> cells and the formation of lipid droplet-like structures were observed using a confocal laser scanning microscope. The neutral lipid components were also analyzed using thin layer chromatography. A diabetic mouse model was established to evaluate the hypoglycemic effects of the main lipid components of <i>A. pasteurianus</i> and their role in repairing tissues such as the pancreas.</p><p><strong>Results: </strong>After comparing the effects of three culture media, namely, brain heart infusion (BHI) medium with 2% glucose, chromium-rich and zinc-rich medium, and mineral salt medium, <i>A. pasteurianus</i> grew well in BHI containing 2% glucose and produced the most lipids. A total of 583 lipid metabolic products was identified, with higher levels of coenzyme Q9 (CoQ9), oleic acid (OA), and wax ester, but no triacylglycerol was observed. It was found that the components that affected lipid metabolism in <i>A. pasteurianus</i> were mainly CoQ9 and OA. They exhibited hypoglycemic effects comparable to metformin in diabetic mice, repaired damaged pancreatic tissues, and did not cause damage to the liver and spleen.</p><p><strong>Conclusion: </strong>Under high-nutrient growth conditions, <i>A. pasteurianus</i> contains abundant lipid components, such as CoQ9 and OA, with good hypoglycemic effects.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"103370"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477450","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":"Dose-dependent L-arginine cardiotoxicity in diabetic cardiomyopathy: Mechanisms and clinical implications.","authors":"Si-Jun Yang","doi":"10.4239/wjd.v16.i6.104851","DOIUrl":"10.4239/wjd.v16.i6.104851","url":null,"abstract":"<p><p>This letter addresses the study in recent publication in the <i>World Journal of Diabetes.</i> The study provides valuable insights and a comprehensive analysis of the effects of L-arginine (L-Arg) supplementation on cardiac health in diabetic rats, highlighting the potential risks associated with high doses of L-Arg. The findings suggest that while low doses of L-Arg may offer some benefits, higher doses can exacerbate myocardial injury through increased oxidative stress, inflammation, and structural disruption. This finding challenges the prevailing point of L-Arg as a universally beneficial supplement and emphasizes the need for further research in its clinical application, particularly in diabetic patients.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"104851"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477439","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":"Erianin mitigates diabetic cardiomyopathy <i>via</i> adenosine monophosphate-activated protein kinase-nuclear factor erythroid 2-related factor 2-heme oxygenase-1 pathway activation.","authors":"Jia-Hui Chen, Xiao-Chun Dai, Zi-Jiao Quan, Xin-Yu Liu","doi":"10.4239/wjd.v16.i6.103685","DOIUrl":"10.4239/wjd.v16.i6.103685","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Erianin is a natural bibenzyl compound extracted from &lt;i&gt;Dendrobium chrysotoxum&lt;/i&gt; and is known for its anti-inflammatory and antioxidant properties.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To explore the possible therapeutic mechanisms of erianin and determine if it can reduce cardiac damage in mice with type 2 diabetes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;High-fat diet and intraperitoneal injections of streptozotocin were used to induce type 2 diabetes mellitus in C57BL/6 mice. Mice were divided into different groups including control, model, and treatment with various doses of erianin (10, 20, and 40 mg/kg) as well as ML-385 + erianin group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Erianin reduced oxidative stress and inflammation and alleviated diabetic cardiomyopathy through the activation of the adenosine monophosphate-activated protein kinase (AMPK)-nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) pathway. Treatments with erianin-M and erianin-H promoted weight stabilization and normalized fasting glucose levels relative to diabetic controls. Echocardiographic assessment demonstrated that erianin dose-dependently enhanced left ventricular systolic function (left ventricular ejection fraction, left ventricular fractional shortening) and mitigated ventricular remodeling (left ventricular internal diameter at end-diastole, left ventricular internal diameter at end-systole; &lt;i&gt;P&lt;/i&gt; &lt; 0.05 &lt;i&gt;vs&lt;/i&gt; model group). No significant differences were observed between the ML-385 + erianin and placebo-treated groups. Histopathological examination through hematoxylin-eosin staining indicated that erianin ameliorated myocardial fiber fragmentation, structural disorganization, inflammatory cell infiltration, and cytolytic damage. Furthermore, it significantly reduced the serum levels of cardiac troponin I, creatine kinase, and its MB isoenzyme. However, the ML-385 + erianin co-treatment failed to alleviate myocardial injury. Metabolic profiling revealed erianin-mediated improvements in glycemic regulation (glycated hemoglobin: &lt;i&gt;P&lt;/i&gt; &lt; 0.001), plasma insulin homeostasis, and lipid metabolism (total cholesterol, triglycerides, low-density lipoprotein cholesterol reduction, and high-density lipoprotein cholesterol restoration; &lt;i&gt;P&lt;/i&gt; &lt; 0.05 &lt;i&gt;vs&lt;/i&gt; model group). Proinflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were markedly suppressed in the erianin-M and erianin-H groups compared with the model group, whereas no significant differences were detected between the model and ML-385 + erianin groups. Oxidative stress parameters showed decreased malondialdehyde levels accompanied by elevated superoxide dismutase and catalase activities in erianin-treated groups, with the most pronounced effects in the erianin-H group (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Western blot analysis confirmed the significant upregulation of proteins associated with the AMPK/Nrf2/HO-1 pathway in erianin-M and erianin-H grou","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"103685"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477442","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}