Acta Diabetologica最新文献

{"title":"Beneficial effects of cell-derived exosomes on diabetic nephropathy: a systematic review and meta-analysis of preclinical evidence.","authors":"Xueli Man, Ting Lin, Zhixuan Xie, Juan Jin, Qiang He","doi":"10.1007/s00592-025-02473-8","DOIUrl":"https://doi.org/10.1007/s00592-025-02473-8","url":null,"abstract":"<p><strong>Aims: </strong>Recent studies indicate that cell-derived exosomes are effective in treating diabetic renal injury, though their precise mechanisms remain unclear. This meta-analysis evaluates the therapeutic efficacy of exosomes in diabetic nephropathy.</p><p><strong>Methods: </strong>In addition to reviewing references and consulting experts, we systematically searched PubMed, Cochrane Library, EMBASE, and Web of Science for studies on exosome therapy for diabetic nephropathy. Seven outcome measures were selected to evaluate efficacy: blood glucose [(fasting blood glucose (FBG) and random blood glucose (RBG)], renal function parameters [serum creatinine (SCR), blood urea nitrogen (BUN), 24-hour urinary protein (24 h UP) and albumin-to-creatinine ratio (UACR)], and inflammatory factors. Study quality was assessed using the SYRCLE risk of bias tool, and data were analyzed using RevMan (version 5.3) software.</p><p><strong>Results: </strong>We included 17 studies involving 288 animals, with follow-up durations ranging from 2 to 14 weeks. Pooled analysis demonstrated that exosome treatment significantly improved GLU (FBG: SMD - 1.39, 95% CI -2.70 to -0.08, P = 0.04; RBG: SMD - 1.29, 95% CI -2.25 to -0.34, P < 0.008), SCR (SMD - 1.45, 95% CI -2.14 to -0.76, P < 0.0001), BUN (SMD - 2.06, 95% CI -3.01 to -1.11, P < 0.0001), 24 UP (SMD - 2.88, 95% CI -3.97 to -1.78, P < 0.00001), and UACR (SMD - 2.00, 95% CI -3.15 to -0.85, P = 0.0007) compared to the diabetic model group. Qualitative analysis revealed that exosomes increased anti-inflammatory factors while reducing pro-inflammatory factors (P < 0.05). No adverse effects of exosomes were reported in any of the included studies.</p><p><strong>Conclusions: </strong>Current evidence indicates that exosomes attenuate diabetic nephropathy progression through anti-inflammatory, anti-fibrotic, anti-apoptotic, and autophagy-inducing mechanisms. To demonstrate the most efficient exosomes and therapeutic parameters for the treatment of diabetic nephropathy, future studies should conduct sizable, randomized, double-blind trials with high-quality, long-term follow-ups.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490343","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}

{"title":"Impact of glucose fluctuations on white matter hyperintensity in type 2 diabetic patients.","authors":"Xin Chen, Wanbing Qian, Xin Wang, Jianrong Yao, Yazhou Ma, Xuegan Lian","doi":"10.1007/s00592-025-02471-w","DOIUrl":"https://doi.org/10.1007/s00592-025-02471-w","url":null,"abstract":"<p><strong>Objectives: </strong>The mean amplitude of glycemic excursion (MAGE) is widely recognized for representing glucose fluctuation extent, its implications in cerebral small vessel disease remain unclear. This study aims to investigate the correlation between MAGE and white matter hyperintensity (WMH).</p><p><strong>Materials and methods: </strong>This cross-sectional study, spanning from March 2021 to October 2022, included 212 type 2 diabetic patients aged between 50 and 80. Participants underwent MRI scans and continuous glucose monitoring. Clinical and laboratory data were compiled for analysis. WMH volumes were evaluated using both the Fazekas visual rating scale and a quantitative approach. Based on Fazekas scores, patients were categorized into low level of WMH (L-WMH, n = 88) and high level of WMH (H-WMH, n = 124) groups.</p><p><strong>Results: </strong>MAGE levels were significantly higher in the H-WMH group compared to the L-WMH group. Time below range [TBR^< 3.9] emerged as an independent risk factor for elevated MAGE. Both MAGE and TBR^< 3.9 independently correlated with an increased WMH burden. Additionally, MAGE was identified as a partial mediator in the relationship between TBR^< 3.9 and WMH volumes.</p><p><strong>Conclusion: </strong>MAGE and hypoglycemia exhibit independent associations with WMH in diabetic patients. Moreover, hypoglycemia may indirectly influence WMH progression through the augmentation of glucose fluctuations.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490344","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}

{"title":"Effect of GLP-1 receptor agonists on bone mineral density, bone metabolism markers, and fracture risk in type 2 diabetes: a systematic review and meta-analysis.","authors":"Yimei Tan, Shuanghua Liu, Qizhi Tang","doi":"10.1007/s00592-025-02468-5","DOIUrl":"https://doi.org/10.1007/s00592-025-02468-5","url":null,"abstract":"<p><strong>Aim: </strong>To systematically assess randomized controlled trials that evaluated the effect of glucagon-like peptide-1 (GLP-1) receptor agonists on fracture incidence, bone mineral density, and bone metabolism markers in individuals with type 2 diabetes.</p><p><strong>Methods: </strong>From database setup to March 21, 2024, a search was conducted across nine Chinese and English databases. The Cochrane Risk of Bias Tool was applied to assess potential bias. Data analysis was performed using RevMan 5.3 and Stata 14.0. Subgroup analysis and meta regression were employed to explore sources of heterogeneity, and publication bias was evaluated using funnel plots and Egger's test.</p><p><strong>Results: </strong>Twenty-five studies were included. The results of the meta-analysis indicated that GLP-1 receptor agonist was not significantly associated with an increased risk of fracture (RR = 0.80; 95% CI 0.47 to 1.36; P = 0.41). Additionally, improvement in lumbar spine BMD (MD = 0.07 g/cm², 95% CI 0.06 to 0.09, P < 0.00001), hip neck BMD (MD = 0.05 g/cm², 95% CI 0.03 to 0.08, P = 0.0001) and total hip BMD (MD = 0.06 g/cm², 95% CI 0.04 to 0.07, P < 0.00001) was superior to the control group. Similarly, GLP-1 receptor agonists significantly improved P1NP (SMD = 0.33, 95% CI 0.07 to 0.59, P = 0.01), OC (MD = 1.46 ug/L, 95% CI 1.10 to 1.83, P < 0.00001), 25-OH-D (SMD = 0.45, 95% CI 0.06 to 0.83, P = 0.02), and b-ALP (MD = 0.91ug/L, 95% CI 0.19 to 1.63, P = 0.01) while reducing β-CTX (SMD = - 0.34, 95% CI - 0.54 to - 0.14, P = 0.001). There was no significant impact on other bone metabolism markers, including N-MID-OT (SMD = 0.43, 95% CI 0.01 to 0.86, P = 0.05), ALP (SMD = - 0.00, 95% CI: - 0.25 to 0.25, P = 0.98), Calcium (MD = 0.00 mmol/L, 95% CI - 0.04 to 0.04, P = 0.94) and Phosphate (MD = 0.02 mmol/L, 95% CI - 0.04 to 0.07, P = 0.57).</p><p><strong>Conclusion: </strong>This meta-analysis demonstrated no significant effect of GLP-1 receptor agonists on elevated fracture risk. There was a statistically significant improvement in BMD and certain bone turnover markers (β-CTX, P1NP, OC, b-ALP, and 25-OH-D). However, due to some limitations, further high-quality clinical studies with sufficient follow-up time are needed to draw more definitive conclusions.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475905","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}

{"title":"Attending an integrated nephrology and diabetology outpatient service can improve diabetic kidney disease treatment: a single-center experience.","authors":"S Wolde Sellasie, C Pecchioli, K Cersosimo, I Nardone, S Zaccaria, A Centi, P Di Perna, P Tatangelo, P Sperti, G Schifano, L Giurato, A Bellia, R Palumbo, L Uccioli","doi":"10.1007/s00592-024-02423-w","DOIUrl":"https://doi.org/10.1007/s00592-024-02423-w","url":null,"abstract":"<p><strong>Background: </strong>Glucose-lowering medications with established reno-protective effects are still underused in Italy. We explored whether attending an integrated nephrology and diabetology (NPD) outpatient service can improve clinical outcomes and adherence to treatment guidelines for diabetic kidney disease (DKD).</p><p><strong>Methods: </strong>We retrospectively included 110 DKD patients (aged 71.1 ± 10.1 years; 74.5% males) having attended the NPD outpatient service of CTO Hospital (Rome) between June and November 2023. Age- and gender-matched control group included DKD patients attending regular Diabetology outpatient service. Drugs prescriptions, clinical and biochemical parameters related to routine evaluation of DKD were collected at first and 6-months control visit.</p><p><strong>Results: </strong>This DKD population was made of 28.2% of patients with urine albumin-creatinine ratio (UACR) > 30 mg/gr, 33.6% with glomerular filtration rate (GFR) < 60 ml/min, 38.2% with both abnormalities. Proportion of patients prescribed with most recent anti-diabetic medications significantly increased after attending the NPD service (for SGLT-2 inhibitors, 54.5 vs. 25.5%, p < 0.01; for GLP1-R agonists, 28.3 vs. 21.8%, p = 0.01), as well as for statins (p < 0.01) and calcium channel-blockers (p = 0.01). During the same observation period we registered significant reduction in LDL cholesterol (p = 0.01) and UACR levels (p = 0.007), with a trend toward improvement in HbA1c and eGFR. Conversely, no significant differences in drugs prescriptions were reported in the control group, except for SGLT-2 inhibitors.</p><p><strong>Conclusions: </strong>Enhanced real-time interaction and collaborative decision-making in an outpatient setting that integrates both diabetology and nephrology expertise can lead to better clinical outcomes and greater adherence to DKD management guidelines, ultimately providing a more comprehensive strategy for cardio-renal risk reduction.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466591","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}

{"title":"Correlation between Sirtuin 1 downregulation and reduced vitamin D receptor expression in patients with diabetic neuropathy.","authors":"Andrea Latini, Giada De Benedittis, Chiara Morgante, Beatrice Gasperini, Ilenia D'Ippolito, Davide Lauro, Giuseppe Novelli, Cinzia Ciccacci, Vincenza Spallone, Paola Borgiani","doi":"10.1007/s00592-025-02463-w","DOIUrl":"https://doi.org/10.1007/s00592-025-02463-w","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to analyse Sirtuin 1 (SIRT1) and Vitamin D receptor (VDR) expression levels in the peripheral blood of patients with type 2 diabetes (T2D), characterized for the presence of diabetic neuropathy (DN), and to evaluate possible genetic factors that could influence the VDR expression levels.</p><p><strong>Methods: </strong>Fifty-one participants with T2D, who underwent neurological assessment for DN were recruited. We quantified the mRNA levels of SIRT1 and VDR in peripheral blood mononuclear cells. Moreover, we analysed the methylation status and the rs2228570 genetic variant of VDR promoter.</p><p><strong>Results: </strong>Patients with DN (n = 32) showed lower expression of SIRT1 (p_corr=0.018) and VDR (p_corr=0.009), compared to those without DN. Furthermore, we observed a positive correlation between the mRNA levels of SIRT1 and VDR (p = 0.01). The expression levels of these genes negatively correlated with the score based on cardiovascular reflex tests (CARTs score). Moreover, the variant allele of rs2228570 in the VDR gene was associated with higher expression of this gene compared to the wild-type allele (p = 0.003).</p><p><strong>Conclusion: </strong>In patients with DN, both SIRT1 and VDR expression levels are reduced and interrelated. Low VDR expression levels could negatively affect SIRT1 transcription, thus influencing all the most pathogenetic pathways of DN regulated by this protein.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456569","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}

{"title":"Diabetes associated with HNF1B: beyond Occam's razor-A case report.","authors":"Carolina Sager-La Ganga, Clara Solà, Karen Castillo, Carme Figueredo, Ignacio Conget","doi":"10.1007/s00592-025-02472-9","DOIUrl":"https://doi.org/10.1007/s00592-025-02472-9","url":null,"abstract":"","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456571","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}

{"title":"Different formulations of semaglutide and oxidative stress in subjects with type 2 diabetes and MASLD: an open-label, real-life study.","authors":"Giovanni Petralli, Alice Del Zoppo, Chiara Rovera, Francesco Raggi, Antonio Salvati, Diego Moriconi, Mariarosaria Distaso, Maurizia Rossana Brunetto, Anna Solini","doi":"10.1007/s00592-025-02466-7","DOIUrl":"https://doi.org/10.1007/s00592-025-02466-7","url":null,"abstract":"<p><strong>Aim: </strong>Semaglutide exerts metabolic effects and cardiovascular protection in type 2 diabetes (T2D), also acting on hepatic steatosis and inflammation. No data are, so far, available on the effect of semaglutide on oxidative stress, neither a comparison of injective (InjS) and oral (OrS) formulations has been performed in subjects with T2D and liver steatosis.</p><p><strong>Methods: </strong>In a real-life, open label, prospective study we compared standard doses of InjS and OrS in targeting liver inflammation and fibrosis and systemic markers of inflammation and oxidative stress by consecutively prescribing InjS or OrS formulation in a 2:1 ratio to sixty T2D + MASLD subjects (T0), observing them for 6 months (T1). Anthropometry, biochemistry and transient elastography (TE) data were collected; hormones, inflammatory cytokines and peroxidation products were measured.</p><p><strong>Results: </strong>At baseline, InjS and OrS subjects were similar, except for waist circumference, liver enzymes and Controlled Attenuation Parameter (CAP), a measure of liver steatosis (InjS > OrS, all p < 0.05). Differences emerged in T0-T1 variation between the formulations in HbA1c, lipid profile, blood pressure. CAP significantly decreased only in InjS. GLP-1 quite similarly increased; insulin, glucagon and GIP did not vary. InjS and OrS did not modify TNFα, IL-10 (an anti-inflammatory cytokine) and MCP-1, while IL-18 was reduced only by InjS. When exploring oxidative stress, AGEs were unaffected, Thiobarbituric acid reactive substances decreased in InjS, 4-Hydroxynonenal was reduced in OrS.</p><p><strong>Conclusion: </strong>In T2D + MASLD subjects, InjS, better than OrS, improves metabolic control; a significant reduction of IL-18 by InjS, and a mild anti-oxidative effect of both formulations are reported for the first time.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424590","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}

{"title":"Case series of a hybrid closed loop therapy system used in pregnancy.","authors":"Trinity L Brigham, Matthew P Klein, Janet K Snell-Bergeon, Sarit Polsky","doi":"10.1007/s00592-025-02469-4","DOIUrl":"https://doi.org/10.1007/s00592-025-02469-4","url":null,"abstract":"<p><strong>Aims: </strong>The effectiveness of Hybrid Closed-Loop (HCL) therapy is rarely studied in type 1 diabetes (T1D) pregnancies.</p><p><strong>Methods: </strong>T1D pregnancies (n = 15) managed off-label during gestation using a commercially available HCL system, Tandem Control IQ, were retrospectively reviewed for baseline characteristics, continuous glucose monitoring (CGM), insulin pump use, insulin doses, and gestational health outcomes. Analyses for unadjusted descriptive statistics of baseline characteristics, glycemic parameters, and gestational health outcomes were performed (mean ± standard deviation (SD) or median with interquartile range (IQR) for continuous variables). Control IQ was used prior to pregnancy by 12 of the 15 cases, with 3 initiating use during gestation.</p><p><strong>Results: </strong>On average, targets were met for pregnancy-specific Time-In-Range (psTIR, 63-140 mg/dL for > 70%) during most of gestation, pregnancy-specific Time-Below-Range (psTBR, < 63 mg/dL for < 4%) throughout gestation, and pregnancy-specific Time-Above-Range (psTAR, > 140 mg/dL for < 25%) from 10- to 17-week gestation. Targets for non-pregnancy TIR (70-180 mg/dL), TAR (> 140 mg/dL), and TBR (< 70 mg/dL) were met preconception and post-partum. Glycemic metrics improved after the first pregnancy visit wherein assistive techniques were applied for off-label use of this HCL system. Gestational health outcomes were as anticipated for T1D pregnancies.</p><p><strong>Conclusions: </strong>Tandem Control IQ HCL therapy used with assistive techniques in 15 T1D pregnancies was associated with improved glycemic levels from the first clinic visit onward.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405101","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}

{"title":"The UBR5 protein facilitates mesangial cell hypertrophy and glycolysis induced by high glucose by increasing the phosphorylation levels of AKT.","authors":"Lin Liao, Qiming Xu, Jie Xu, Jie Chen, Wenrui Liu, Wenhao Chen, Yunqing Tang, Lianxiang Duan, Yue Guo, Ziyang Liu, Pengyu Tao, Yu Cao, Jianrao Lu, Jing Hu","doi":"10.1007/s00592-025-02464-9","DOIUrl":"https://doi.org/10.1007/s00592-025-02464-9","url":null,"abstract":"<p><strong>Aims: </strong>One of the primary pathological features in the early stages of diabetic nephropathy is mesangial cell (MC) hypertrophy in the glomerulus. Considering the role of E3 ubiquitin ligases in regulating MC hypertrophy, the aim of this study was to identify the functional ubiquitin protein ligase E3 component N-recognin 5 (UBR5) during MC hypertrophy under high glucose conditions.</p><p><strong>Methods: </strong>Human MCs (HMCs) transduced with UBR5 silencing or overexpression vector were treated with high glucose, AKT inhibitor, or glycolysis inhibitor. Cell proliferation, cell cycle, hypertrophy and glycolysis were evaluated in the HMCs after indicated treatment. m6A methylated RNA immunoprecipitation, luciferase reporter assay, and RNA immunoprecipitation were performed to determine the regulation of UBR5 by Wilms tumor 1-associating protein (WTAP)/insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) induced m6A modification. Western blot was performed to determine the protein expression levels.</p><p><strong>Results: </strong>UBR5 expression was upregulated in db/db mice and in high glucose-induced HMCs. UBR5 silencing inhibited high glucose-induced HMC cell cycle arrest, cell hypertrophy, and glycolysis. UBR5 facilitated HMC hypertrophy and glycolysis by promoting the phosphorylation levels of AKT. Additionally, the promoting effect of glycolysis on cell hypertrophy were also elucidated. Further investigation into upstream regulators revealed that WTAP promoted m6A modification of UBR5 through the m6A reader IGF2BP1.</p><p><strong>Conclusions: </strong>Our study unveils a novel mechanism involved in high glucose-induced cell hypertrophy, offering new insights into the understanding and treatment of early pathological mechanisms in diabetic nephropathy.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405104","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}

{"title":"Identify of blood glucose metabolism regulation pathways and related proteins in the db/db mouse model through iTRAQ quantitative mass spectrometry.","authors":"Yilin Yue, Shanshan Dong, Zhihui Wu, Yongqing Dong, Qingpei Chen, Hong Wang, Chaowu Liu, Deguang Yang","doi":"10.1007/s00592-025-02465-8","DOIUrl":"https://doi.org/10.1007/s00592-025-02465-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Diabetes cardiomyopathy (DCM) has become the main cause of death of diabetes patients due to heart failure. As the initial unclear symptoms and complex underlying pathological mechanisms, it presents significant challenges for early diagnosis. It is essential to explore valuable biomarkers to enhance our understanding involved in DCM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Twelve-week-old db/db model mice (diabetes group) and normal mice (control group) were maintained in a specific pathogen-free (SPF) environment. Body weight, blood glucose, and insulin levels were measured regularly. At 26 weeks, cardiac tissue was collected to assess oxidative stress, inflammatory factors, and fibrosis markers, followed by histopathological examination. Meanwhile, iTRAQ-based quantitative mass spectrometry was employed to identify differentially expressed proteins (DEPs) in cardiac tissue. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods were utilized to analyze their biological functions and signaling pathways. Furthermore, specific proteins and their associated signaling pathways related to blood glucose regulation were validated in cardiac tissue and myocardial cells using western blot and immunofluorescence analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The mice in the control group were active and exhibited healthy growth, whereas those in the diabetes group showed increased food and water intake. Furthermore, there were significant elevations in blood glucose concentration, insulin levels, and body weight in the diabetes group. Histopathological examinations revealed that the myocardium in the diabetes group was markedly hypertrophic due to persistent hyperglycemia, accompanied by muscle fiber disarray, nuclear damage, and a significant increase in the expression of oxidative stress and inflammatory factors. Mass spectrometry analysis identified a total of 107 DEPs, comprising 83 up-regulated and 24 down-regulated proteins. Notably, the most significant difference was observed in the regulation of the glycogen metabolism enzyme (PYGM). GO and KEGG analyses indicated that the DEPs were primarily involved in glycogen metabolism, catalysis, and oxidative stress, with signaling pathways related to fatty acid metabolism, the PPAR pathway, insulin resistance, and the tricarboxylic acid cycle. Subsequent immunofluorescence and western blot analysis confirmed that hyperglycemia inhibits the PI3K/AKT signaling pathway and upregulates the expression of PYGM. Conversely, the knockout of PYGM significantly enhanced the activity of the PI3K/AKT signaling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The research suggests that the inhibition of PYGM enhances the activity of the PI3K/AKT signaling pathway in patients with DCM, and then help to reduce blood glucose levels. This molecular mechanism exerts a protective effect on DCM. These findings highlight the potential of targeting PYGM as a novel biomarker for the ear","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389795","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}