Diabetes最新文献_第2页

Diroximel Fumarate Acts Through Nrf2 to Attenuate Methylglyoxal-Induced Nociception in Mice and Decrease ISR Activation in DRG Neurons. 富马酸地洛西梅尔通过Nrf2作用于小鼠甲基乙二醛诱导的伤害感受，降低DRG神经元的ISR激活。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db23-1025

Muhammad Saad Yousuf, Marisol Mancilla Moreno, Brodie J Woodall, Vikram Thakur, Jiahe Li, Lucy He, Rohita Arjarapu, Danielle Royer, Jennifer Zhang, Munmun Chattopadhyay, Peter M Grace, Theodore J Price

{"title":"Diroximel Fumarate Acts Through Nrf2 to Attenuate Methylglyoxal-Induced Nociception in Mice and Decrease ISR Activation in DRG Neurons.","authors":"Muhammad Saad Yousuf, Marisol Mancilla Moreno, Brodie J Woodall, Vikram Thakur, Jiahe Li, Lucy He, Rohita Arjarapu, Danielle Royer, Jennifer Zhang, Munmun Chattopadhyay, Peter M Grace, Theodore J Price","doi":"10.2337/db23-1025","DOIUrl":"10.2337/db23-1025","url":null,"abstract":"Diabetic neuropathic pain is associated with elevated plasma levels of methylglyoxal (MGO). MGO is a metabolite of glycolysis that causes pain hypersensitivity in mice by stimulating the phosphorylation of eukaryotic initiation factor 2α (p-eIF2α) and subsequently activating the integrated stress response (ISR). We first established that Zucker diabetic fatty rats have enhanced MGO signaling, engage ISR, and develop pain hypersensitivity. Since nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of antioxidant proteins that neutralize MGO, we hypothesized that fumarates, like diroximel fumarate (DRF), will stimulate Nrf2 signaling, and prevent MGO-induced ISR and pain hypersensitivity. DRF (100 mg/kg) treated animals were protected from developing MGO (20 ng) induced mechanical and cold hypersensitivity. Mechanistically, DRF treatment protected against MGO-induced increase in p-eIF2α levels in the sciatic nerve and reduced loss of intraepidermal nerve fiber density. Using Nrf2 knockout mice, we demonstrate that Nrf2 is necessary for the antinociceptive effects of DRF. Cotreatment of MGO (1 µmol/L) with monomethyl fumarate (10, 20, and 50 µmol/L), the active metabolite of DRF, prevented ISR in both mouse and human dorsal root ganglia neurons. Our data show that targeting Nrf2 with DRF is a strategy to potentially alleviate pain associated with elevated MGO levels.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"827-837"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

β-Cell Benchmarks: Defining Predictive Outcomes in Islet Transplantation. β-细胞基准：确定胰岛移植的预测结果。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/dbi24-0054

Shareen Forbes

引用次数: 0

Of Mice and Men: Toward a Better Model of Diabetic Cardiomyopathy With Application in Female Animals. 小鼠和男性：在雌性动物中应用更好的糖尿病性心肌病模型。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/dbi25-0010

Jordan S F Chan, John R Ussher

引用次数: 0

Differential Effects of Retinol-Binding Protein 3 and Anti-VEGF Antibodies on Retinal Dysfunctions in Diabetic Retinopathy. 视黄醇结合蛋白3和抗vegf抗体在糖尿病视网膜病变视网膜功能障碍中的差异作用。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db24-0822

Qin Li, Satoru Onizuka, Kyoungmin Park, Mingming Ma, Ward Fickweiler, Hyunseok Park, Qian Li, Fabricio Simao, Jared Boisclair, Maha Sharawy, I-Hsien Wu, Marc Gregory Yu, Lloyd P Aiello, Jennifer K Sun, George L King

{"title":"Differential Effects of Retinol-Binding Protein 3 and Anti-VEGF Antibodies on Retinal Dysfunctions in Diabetic Retinopathy.","authors":"Qin Li, Satoru Onizuka, Kyoungmin Park, Mingming Ma, Ward Fickweiler, Hyunseok Park, Qian Li, Fabricio Simao, Jared Boisclair, Maha Sharawy, I-Hsien Wu, Marc Gregory Yu, Lloyd P Aiello, Jennifer K Sun, George L King","doi":"10.2337/db24-0822","DOIUrl":"10.2337/db24-0822","url":null,"abstract":"Anti-vascular endothelial growth factor (anti-VEGF) therapies are effective treatment for severe diabetic retinopathy (DR) and macular edema, but a significant subset of people had inadequate response to anti-VEGF intervention. Because elevation or overexpression of retinol binding protein 3 (RBP3) decreases risks for retinal pathologies and progression to severe DR, we compared the therapeutic profiles of RBP3 and anti-VEGF antibody to normalize retinal dysfunctions induced by diabetes. Intravitreous injection of recombinant human RBP3 (rhRBP3) and anti-VEGF antibody (namely, bevacizumab) inhibited retinal vascular permeability in Lewis rats induced by VEGF-A or after 2 months of diabetes induced by streptozotocin, in parallel with reductions of retinal VEGF and VEGF receptor 2 expressions and tyrosine phosphorylation of VEGF receptor. Only rhRBP3 ameliorated diabetes-induced reduction of neural retinal function, measured by electroretinogram. Furthermore, rhRBP3 reduced retinal expressions of inflammatory cytokines (TNF-α and IL-6) in retinal pigmented epithelial and Müller cells exposed to hyperglycemia. Metabolic studies, using a Seahorse flux analyzer, showed only rhRBP3 normalized retinal glycolytic rates in diabetic rats. Thus, both intravitreous anti-VEGF antibody and RBP3 injections normalized retinal vascular dysfunctions caused by diabetes. Only RBP3 targeted both neural and vascular retina to reduce glycolytic rates, reverse neural-retinal dysfunctions, and reduce inflammatory cytokines induced by diabetes, to delay early changes of DR.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"787-797"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Padi4-Dependent NETosis Enables Diet-Induced Gut Hyperpermeability, Translating Dysbiosis Into Systemic Inflammation and Dysmetabolism. 依赖于 Padi4 的 NETosis 使饮食诱导的肠道高渗透性得以实现，并将菌群失调转化为全身性炎症和代谢紊乱。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db24-0481

Mattia Albiero, Ludovica Migliozzi, Carlotta Boscaro, Anna Rodella, Stefano Ciciliot, Francesco Ivan Amendolagine, Valentina Scattolini, Laura Treu, Roberta Cappellari, Paola Lanuti, Annica Barizza, Gaia Codolo, Alessandra Giannella, Giulio Ceolotto, Tatiana Varanita, Luca Prevedello, Mirto Foletto, Sara Bogialli, Stefano Campanaro, Angelo Avogaro, Gian Paolo Fadini

{"title":"Padi4-Dependent NETosis Enables Diet-Induced Gut Hyperpermeability, Translating Dysbiosis Into Systemic Inflammation and Dysmetabolism.","authors":"Mattia Albiero, Ludovica Migliozzi, Carlotta Boscaro, Anna Rodella, Stefano Ciciliot, Francesco Ivan Amendolagine, Valentina Scattolini, Laura Treu, Roberta Cappellari, Paola Lanuti, Annica Barizza, Gaia Codolo, Alessandra Giannella, Giulio Ceolotto, Tatiana Varanita, Luca Prevedello, Mirto Foletto, Sara Bogialli, Stefano Campanaro, Angelo Avogaro, Gian Paolo Fadini","doi":"10.2337/db24-0481","DOIUrl":"10.2337/db24-0481","url":null,"abstract":"Microbial signals trigger the release of neutrophil extracellular traps (NETs) through peptidyl arginine deiminase 4 (PADI4). In turn, NETosis can propagate inflammation to distant tissues. We hypothesize that PADI4 mediates the interactions between diet-modified microbiota and host metabolism. We report that in the adipose tissue of individuals with obesity, NETosis was associated with dysglycemia. In mice, high-fat diet (HFD) induced not only dysmetabolism and metainflammation but also local and systemic signs of NETosis. Deleting Padi4 in hematopoietic cells (Padi4KO) blunted liver and adipose inflammation and improved metabolism under HFD. While NETs were able to disrupt gut epithelial integrity, abrogating NETosis preserved intestinal barrier function and mitigated metabolic endotoxemia due to HFD. Padi4 deletion did not prevent diet-induced dysbiosis, but Padi4KO mice were protected from intestinal hyperpermeability and metabolic impairment due to the transfer of HFD-modified microbiota. As Padi4KO did not blunt the dysmetabolic effects of lipopolysaccharide, we concluded that NETosis operates at the microbiota-intestinal interface, inducing hyperpermeability and the systemic spillover of bacterial-derived products, paving the way to the metabolic consequences of HFD. Finally, pharmacologic PADI4 inhibition recapitulated findings obtained in Padi4KO mice on metabolism and liver steatosis, thereby uncovering a druggable role for PADI4 in mediating the metabolic effects of unhealthy microbiota.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"705-719"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of the Effects of SGLT-2i Versus GLP-1RA on Cardiovascular and Renal Outcomes in Patients With Type 2 Diabetes, Based on Baseline Renal Function. 基于基线肾功能的SGLT-2i与GLP-1RA对2型糖尿病患者心血管和肾脏预后影响的比较

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db24-0688

Yu Wang, Chao Xia, Manna Li, Gaosi Xu

{"title":"Comparison of the Effects of SGLT-2i Versus GLP-1RA on Cardiovascular and Renal Outcomes in Patients With Type 2 Diabetes, Based on Baseline Renal Function.","authors":"Yu Wang, Chao Xia, Manna Li, Gaosi Xu","doi":"10.2337/db24-0688","DOIUrl":"10.2337/db24-0688","url":null,"abstract":"Finding no head-to-head research evaluating the cardiovascular and renal benefits of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) in patients with type 2 diabetes (T2D) at different baseline renal function, we performed a network meta-analysis to compare the two drugs indirectly. Systematic literature searches were conducted of the PubMed, Cochrane Library, Web of Science, and Embase databases, covering their inception until 7 January 2025. Randomized controlled trials (RCTs) comparing the effects of SGLT-2i and GLP-1RA in T2D with different glomerular filtration rates (eGFRs) were selected. Results were reported as risk ratios (RRs) with corresponding 95% CIs. Finally, 10 RCTs involving 87,334 patients with T2D were included. In patients with an eGFR >90 mL/min/1.73 m2, GLP-1RA exhibited a superior ability to reduce the risk of all-cause death compared with SGLT-2i (RR 0.75; 95% CI 0.58, 0.97), but it was less effective in reducing the risk of renal outcome (RR 1.80; 95% CI 1.15, 2.84) in patients with an eGFR 60-90 mL/min/1.73 m2. Conversely, in patients with eGFR 30-60 and 60-90 mL/min/1.73 m2, GLP-1RA did not show an advantage in reducing the risk of hospitalization for heart failure (RR 1.87 [95% CI 1.15, 3.04] and 1.37 [95% CI 1.05, 1.78], respectively).Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"672-681"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial Ceramides and Weight Loss: Unanswered Questions and Future Directions. 线粒体神经酰胺和减肥：未解之谜和未来方向。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db25-0148

Adam Astrada

引用次数: 0

Metabolic Dysfunction Associated With Alterations in Gut Microbiota in Adolescents With Obesity. 肥胖青少年肠道菌群改变与代谢功能障碍相关

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db24-0866

Alessandra Granato, Quin Yuhui Xie, Anthony Wong, Christopher Yau, Rebecca Noseworthy, Tina Chen, Connor Gianetto-Hill, Emma Allen-Vercoe, Cynthia J Guidos, Jill K Hamilton, Jayne S Danska

{"title":"Metabolic Dysfunction Associated With Alterations in Gut Microbiota in Adolescents With Obesity.","authors":"Alessandra Granato, Quin Yuhui Xie, Anthony Wong, Christopher Yau, Rebecca Noseworthy, Tina Chen, Connor Gianetto-Hill, Emma Allen-Vercoe, Cynthia J Guidos, Jill K Hamilton, Jayne S Danska","doi":"10.2337/db24-0866","DOIUrl":"10.2337/db24-0866","url":null,"abstract":"Obesity in childhood is associated with adulthood obesity, type 2 diabetes (T2D), and future metabolic complications. The gut microbiota is a modifier of host metabolic function with altered bacterial composition associated with disease risk. Few studies have investigated the relationships among metabolic disease, inflammation, and the gut microbiota in youth, in whom these connections likely originate. Here, we characterized the gut microbiome of a cohort of 56 adolescents with obesity and without diabetes using fecal DNA sequencing with absolute bacterial quantitation together with immune and metabolic profiling. We observed multi-log order variation in absolute bacterial biomass dependent on host environment and associated with bacterial taxonomic composition based on a nested case-control comparison. Participants with higher biomass displayed a healthier phenotype with higher gut microbiome diversity; lower abundance of taxa associated with inflammation and pathogenicity, such as Escherichia coli; and lower levels of neutrophil activities. Further association analysis revealed sex-dependent variation, with higher levels of insulin resistance, fasting triglycerides, and markers of neutrophil activities in male adolescents with lower bacterial biomass. Together, these results suggest that intestinal bacterial biomass and composition are associated with metabolic and inflammatory dysregulation evident before T2D diagnosis and identify sex differences in microbiome-associated metabolic dysfunction in adolescents with obesity.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"720-733"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unilateral Primary Aldosteronism Lacking KCNJ5 Somatic Mutations Is Associated With an Elevated Risk of New-Onset Diabetes. 缺乏KCNJ5体细胞突变的单侧原发性醛固酮增多症与新发糖尿病风险升高相关

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db23-0273

Chieh-Kai Chan, Wei-Shiung Yang, Yen-Hung Lin, Vin-Cent Wu, Jeff S Chueh

{"title":"Unilateral Primary Aldosteronism Lacking KCNJ5 Somatic Mutations Is Associated With an Elevated Risk of New-Onset Diabetes.","authors":"Chieh-Kai Chan, Wei-Shiung Yang, Yen-Hung Lin, Vin-Cent Wu, Jeff S Chueh","doi":"10.2337/db23-0273","DOIUrl":"10.2337/db23-0273","url":null,"abstract":"The association between KCNJ5 mutations and the risk of developing new-onset diabetes (NOD) in patients with unilateral primary aldosteronism (uPA) remains underexplored. To investigate this association, we conducted a longitudinal study using data from the Taiwan Primary Aldosteronism Investigation database. Our sample included 360 patients with uPA who underwent adrenalectomy between 2012 and 2017, 191 (53.1%) of whom had KCNJ5 mutations in their adrenal adenomas. We found that patients with uPA harboring KCNJ5 mutations had a higher rate of complete clinical success (69.5% vs. 43.8%; P < 0.01) and complete biochemical success (93.8% vs. 86.6%; P = 0.04) compared with those without KCNJ5 mutations at 6 months to 1 year after adrenalectomy. Over an average follow-up period of 8.5 years, multivariate Cox regression analysis revealed that patients with uPA with KCNJ5 mutations had a significantly lower risk of developing NOD (hazard ratio [HR] 0.41; 95% CI 0.17-0.996; P = 0.049). Additionally, we identified higher BMI (HR 1.23; 95% CI 1.11-1.37; P < 0.01) and lower estimated glomerular filtration rate (eGFR; HR 0.98; 95% CI 0.97-0.99; P = 0.01) as potential predictors of NOD based on baseline characteristics. The association between patients with uPA without KCNJ5 mutations and higher incidence of NOD was less pronounced in subgroups characterized by younger age, higher BMI, higher eGFR, and lower potassium levels. In conclusion, patients with uPA without KCNJ5 mutations had a higher incidence of NOD, with 13.6% affected during long-term follow-up. Our findings suggest that patients with uPA without KCNJ5 mutations may require more frequent follow-up for NOD after adrenalectomy.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"850-859"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diabetes Spotlight: Kirk Habegger, PhD: The Impact of Glucagon on Metabolic Processes. 糖尿病焦点：Kirk Habegger博士：胰高血糖素对代谢过程的影响。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/dbi25-0015

Benjamin Page

引用次数: 0