Diabetes最新文献

{"title":"Characterizing Common and Rare Variations in Nontraditional Glycemic Biomarkers Using Multivariate Approaches on Multiancestry ARIC Study.","authors":"Debashree Ray, Stephanie J Loomis, Sowmya Venkataraghavan, Jiachen Zhang, Adrienne Tin, Bing Yu, Nilanjan Chatterjee, Elizabeth Selvin, Priya Duggal","doi":"10.2337/db23-0318","DOIUrl":"10.2337/db23-0318","url":null,"abstract":"<p><p>Genetic studies of nontraditional glycemic biomarkers, glycated albumin and fructosamine, can shed light on unknown aspects of type 2 diabetes genetics and biology. We performed a multiphenotype genome-wide association study of glycated albumin and fructosamine from 7,395 White and 2,016 Black participants in the Atherosclerosis Risk in Communities (ARIC) study on common variants from genotyped/imputed data. We discovered two genome-wide significant loci, one mapping to a known type 2 diabetes gene (ARAP1/STARD10) and another mapping to a novel region (UGT1A complex of genes), using multiomics gene-mapping strategies in diabetes-relevant tissues. We identified additional loci that were ancestry- and sex-specific (e.g., PRKCA in African ancestry, FCGRT in European ancestry, TEX29 in males). Further, we implemented multiphenotype gene-burden tests on whole-exome sequence data from 6,590 White and 2,309 Black ARIC participants. Ten variant sets annotated to genes across different variant aggregation strategies were exome-wide significant only in multiancestry analysis, of which CD1D, EGFL7/AGPAT2, and MIR126 had notable enrichment of rare predicted loss of function variants in African ancestry despite smaller sample sizes. Overall, 8 of 14 discovered loci and genes were implicated to influence these biomarkers via glycemic pathways, and most of them were not previously implicated in studies of type 2 diabetes. This study illustrates improved locus discovery and potential effector gene discovery by leveraging joint patterns of related biomarkers across the entire allele frequency spectrum in multiancestry analysis. Future investigation of the loci and genes potentially acting through glycemic pathways may help us better understand the risk of developing type 2 diabetes.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1537-1550"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312587","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}

{"title":"Leucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling.","authors":"Emily R Knuth, Hannah R Foster, Erli Jin, Maia H Ekstrand, Jakob G Knudsen, Matthew J Merrins","doi":"10.2337/db23-1013","DOIUrl":"10.2337/db23-1013","url":null,"abstract":"<p><p>Glucagon is critical for the maintenance of blood glucose, however nutrient regulation of pancreatic α-cells remains poorly understood. Here, we identified a role of leucine, a well-known β-cell fuel, in the α-cell-intrinsic regulation of glucagon release. In islet perifusion assays, physiologic concentrations of leucine strongly inhibited alanine- and arginine-stimulated glucagon secretion from human and mouse islets under hypoglycemic conditions. Mechanistically, leucine dose-dependently reduced α-cell cAMP, independently of Ca2+, ATP/ADP, or fatty acid oxidation. Leucine also reduced α-cell cAMP in islets treated with somatostatin receptor 2 antagonists or diazoxide, compounds that limit paracrine signaling from β/δ-cells. Studies in dispersed mouse islets confirmed an α-cell-intrinsic effect. The inhibitory effect of leucine on cAMP was mimicked by glucose, α-ketoisocaproate, succinate, and the glutamate dehydrogenase activator BCH and blocked by cyanide, indicating a mechanism dependent on mitochondrial metabolism. Glucose dose-dependently reduced the impact of leucine on α-cell cAMP, indicating an overlap in function; however, leucine was still effective at suppressing glucagon secretion in the presence of elevated glucose, amino acids, and the incretin GIP. Taken together, these findings show that leucine plays an intrinsic role in limiting the α-cell secretory tone across the physiologic range of glucose levels, complementing the inhibitory paracrine actions of β/δ-cells.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1426-1439"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319341","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}

{"title":"Recent Progress in Glucose-Responsive Insulin.","authors":"Yun Liu, Shiqi Wang, Zejun Wang, Jicheng Yu, Jinqiang Wang, John B Buse, Zhen Gu","doi":"10.2337/dbi23-0028","DOIUrl":"10.2337/dbi23-0028","url":null,"abstract":"<p><p>Insulin replacement therapy is indispensable in the treatment of type 1 and advanced type 2 diabetes. However, insulin's clinical application is challenging due to its narrow therapeutic index. To mitigate acute and chronic risks of glucose excursions, glucose-responsive insulin (GRI) has long been pursued for clinical application. By integrating GRI with glucose-sensitive elements, GRI is capable of releasing or activating insulin in response to plasma or interstitial glucose levels without external monitoring, thereby improving glycemic control and reducing hypoglycemic risk. In this Perspective, we first introduce the history of GRI development and then review major glucose-responsive components that can be leveraged to control insulin delivery. Subsequently, we highlight the recent advances in GRI delivery carriers and insulin analogs. Finally, we provide a look to the future and the challenges of clinical application of GRI.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1377-1388"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302288","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}

{"title":"The Longitudinal Effect of Diabetes-Associated Variation in TCF7L2 on Islet Function in Humans.","authors":"Maya Zeini, Marcello C Laurenti, Aoife M Egan, Kalpana Muthusamy, Anisha Ramar, Emma Vella, Kent R Bailey, Claudio Cobelli, Chiara Dalla Man, Adrian Vella","doi":"10.2337/db24-0192","DOIUrl":"10.2337/db24-0192","url":null,"abstract":"<p><p>The T allele at rs7903146 in TCF7L2 increases the rate of conversion from prediabetes to type 2 diabetes. This has been associated with impaired β-cell function and with defective suppression of α-cell secretion by glucose. However, the temporal relationship of these abnormalities is uncertain. To study the longitudinal changes in islet function, we recruited 128 subjects, with 67 homozygous for the diabetes-associated allele (TT) at rs7903146 and 61 homozygous for the protective allele. Subjects were studied on two occasions, 3 years apart, using an oral 75-g glucose challenge. The oral minimal model was used to quantitate β-cell function; the glucagon secretion rate was estimated from deconvolution of glucagon concentrations. Glucose tolerance worsened in subjects with the TT genotype. This was accompanied by impaired postchallenge glucagon suppression but appropriate β-cell responsivity to rising glucose concentrations. These data suggest that α-cell abnormalities associated with the TT genotype (rs7903146) occur early and may precede β-cell dysfunction in people as they develop glucose intolerance and type 2 diabetes.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1440-1446"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312593","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}

{"title":"The Role of Activator Protein-1 Complex in Diabetes-Associated Atherosclerosis: Insights From Single-Cell RNA Sequencing.","authors":"Abdul Waheed Khan, Misbah Aziz, Karly C Sourris, Man K S Lee, Aozhi Dai, Anna M D Watson, Scott Maxwell, Arpeeta Sharma, Ying Zhou, Mark E Cooper, Anna C Calkin, Andrew J Murphy, Sara Baratchi, Karin A M Jandeleit-Dahm","doi":"10.2337/db23-0167","DOIUrl":"10.2337/db23-0167","url":null,"abstract":"<p><p>Despite advances in treatment, atherosclerotic cardiovascular disease remains the leading cause of death in patients with diabetes. Even when risk factors are mitigated, the disease progresses, and thus, newer targets need to be identified that directly inhibit the underlying pathobiology of atherosclerosis in diabetes. A single-cell sequencing approach was used to distinguish the proatherogenic transcriptional profile in aortic cells in diabetes using a streptozotocin-induced diabetic Apoe-/- mouse model. Human carotid endarterectomy specimens from individuals with and without diabetes were also evaluated via immunohistochemical analysis. Further mechanistic studies were performed in human aortic endothelial cells (HAECs) and human THP-1-derived macrophages. We then performed a preclinical study using an activator protein-1 (AP-1) inhibitor in a diabetic Apoe-/- mouse model. Single-cell RNA sequencing analysis identified the AP-1 complex as a novel target in diabetes-associated atherosclerosis. AP-1 levels were elevated in carotid endarterectomy specimens from individuals with diabetes compared with those without diabetes. AP-1 was validated as a mechanosensitive transcription factor via immunofluorescence staining for regional heterogeneity of endothelial cells of the aortic region exposed to turbulent blood flow and by performing microfluidics experiments in HAECs. AP-1 inhibition with T-5224 blunted endothelial cell activation as assessed by a monocyte adhesion assay and expression of genes relevant to endothelial function. Furthermore, AP-1 inhibition attenuated foam cell formation. Critically, treatment with T-5224 attenuated atherosclerosis development in diabetic Apoe-/- mice. This study has identified the AP-1 complex as a novel target, the inhibition of which treats the underlying pathobiology of atherosclerosis in diabetes.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1495-1512"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437940","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}

{"title":"The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.","authors":"Mariana Byndloss, Suzanne Devkota, Frank Duca, Jan Hendrik Niess, Max Nieuwdorp, Marju Orho-Melander, Yolanda Sanz, Valentina Tremaroli, Liping Zhao","doi":"10.2337/dbi24-0028","DOIUrl":"10.2337/dbi24-0028","url":null,"abstract":"<p><p>This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single-time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1391-1410"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443974","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}

{"title":"Diabetic Wound Keratinocytes Induce Macrophage JMJD3-Mediated Nlrp3 Expression via IL-1R Signaling.","authors":"Sonya J Wolf, Christopher O Audu, Jadie Y Moon, Amrita D Joshi, William J Melvin, Emily C Barrett, Kevin Mangum, Gabriela Saldana de Jimenez, Sabrina Rocco, Sam Buckley, Zara Ahmed, Rachael Wasikowski, J Michelle Kahlenberg, Lam C Tsoi, Johann E Gudjonsson, Katherine A Gallagher","doi":"10.2337/db23-0968","DOIUrl":"10.2337/db23-0968","url":null,"abstract":"<p><p>Macrophage (Mφ) plasticity is critical for normal wound repair; however, in type 2 diabetic wounds, Mφs persist in a low-grade inflammatory state that prevents the resolution of wound inflammation. Increased NLRP3 inflammasome activity has been shown in diabetic wound Mφs; however, the molecular mechanisms regulating NLRP3 expression and activity are unclear. Here, we identified that diabetic wound keratinocytes induce Nlrp3 gene expression in wound Mφs through IL-1 receptor-mediated signaling, resulting in enhanced inflammasome activation in the presence of pathogen-associated molecular patterns and damage-associated molecular patterns. We found that IL-1α is increased in human and murine wound diabetic keratinocytes compared with nondiabetic controls and directly induces Mφ Nlrp3 expression through IL-1 receptor signaling. Mechanistically, we report that the histone demethylase, JMJD3, is increased in wound Mφs late post-injury and is induced by IL-1α from diabetic wound keratinocytes, resulting in Nlrp3 transcriptional activation through an H3K27me3-mediated mechanism. Using genetically engineered mice deficient in JMJD3 in myeloid cells (Jmjd3f/flyz2Cre+), we demonstrate that JMJD3 controls Mφ-mediated Nlrp3 expression during diabetic wound healing. Thus, our data suggest a role for keratinocyte-mediated IL-1α/IL-1R signaling in driving enhanced NLRP3 inflammasome activity in wound Mφs. These data also highlight the importance of cell cross-talk in wound tissues and identify JMJD3 and the IL-1R signaling cascade as important upstream therapeutic targets for Mφ NLRP3 inflammasome hyperactivity in nonhealing diabetic wounds.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1462-1472"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312590","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}

{"title":"Development of Novel Tools for Dissection of Central Versus Peripheral Dopamine D2-Like Receptor Signaling in Dysglycemia.","authors":"Alessandro Bonifazi, Michael Ellenberger, Zachary J Farino, Despoina Aslanoglou, Rana Rais, Sandra Pereira, José O Mantilla-Rivas, Comfort A Boateng, Amy J Eshleman, Aaron Janowsky, Margaret K Hahn, Gary J Schwartz, Barbara S Slusher, Amy Hauck Newman, Zachary Freyberg","doi":"10.2337/db24-0175","DOIUrl":"10.2337/db24-0175","url":null,"abstract":"<p><p>Dopamine (DA) D2-like receptors in both the central nervous system (CNS) and the periphery are key modulators of metabolism. Moreover, disruption of D2-like receptor signaling is implicated in dysglycemia. Yet, the respective metabolic contributions of CNS versus peripheral D2-like receptors, including D2 (D2R) and D3 (D3R) receptors, remain poorly understood. To address this, we developed new pharmacological tools, D2-like receptor agonists with diminished and delayed blood-brain barrier capability, to selectively manipulate D2R/D3R signaling in the periphery. We designated bromocriptine methiodide (BrMeI), a quaternary methiodide analog of D2R/D3R agonist and diabetes drug bromocriptine, as our lead compound based on preservation of D2R/D3R binding and functional efficacy. We then used BrMeI and unmodified bromocriptine to dissect relative contributions of CNS versus peripheral D2R/D3R signaling in treating dysglycemia. Systemic administration of bromocriptine, with unrestricted access to CNS and peripheral targets, significantly improved both insulin sensitivity and glucose tolerance in obese, dysglycemic mice in vivo. In contrast, metabolic improvements were attenuated when access to bromocriptine was restricted either to the CNS through intracerebroventricular administration or delayed access to the CNS via BrMeI. Our findings demonstrate that the coordinated actions of both CNS and peripheral D2-like receptors are required for correcting dysglycemia. Ultimately, the development of a first-generation of drugs designed to selectively target the periphery provides a blueprint for dissecting mechanisms of central versus peripheral DA signaling and paves the way for novel strategies to treat dysglycemia.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1411-1425"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312589","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}

{"title":"Regulatory Role of NF-κB on HDAC2 and Tau Hyperphosphorylation in Diabetic Encephalopathy and the Therapeutic Potential of Luteolin.","authors":"Qian Fu, Yilin Song, Zhaoke Ling, Jie Liu, Qingqing Kong, Xin Hao, Ting Xu, Qiang Zhang, Yi Liu","doi":"10.2337/db23-0969","DOIUrl":"10.2337/db23-0969","url":null,"abstract":"<p><p>Diabetic encephalopathy (DE) is a severe complication of the central nervous system associated with diabetes. In this study, we investigated the regulatory role of mammalian target of rapamycin (mTOR) on nuclear factor κB (NF-κB) in mice with DE, and the neuroprotective effect and therapeutic mechanisms of luteolin, a natural flavonoid compound with anti-inflammatory, antioxidant, and neuroprotective properties. The results indicated that treatment with luteolin improved the degree of cognitive impairment in mice with DE. It also decreased the levels of phosphorylated mTOR, phosphorylated NF-κB, and histone deacetylase 2 (HDAC2) and increased the expression of brain-derived neurotrophic factor and synaptic-related proteins. Furthermore, protein-protein interaction and the Gene Ontology analysis revealed that luteolin was involved in the regulatory network of HDAC2 expression through the mTOR/NF-κB signaling cascade. Our bioinformatics and molecular docking results indicated that luteolin may also directly target HDAC2, as an HDAC2 inhibitor, to alleviate DE, complementing mTOR/NF-κB signaling inhibition. Analysis of luteolin's target proteins and their interactions suggest an effect on HDAC2 and cognition. In conclusion, HDAC2 and tau hyperphosphorylation are regulated by the mTOR/NF-κB signaling cascade in DE, and luteolin is found to reverse these effects, demonstrating its protective role in DE.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1513-1526"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312592","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}

{"title":"Complement Factor C1q Mediates Vascular Endothelial Dysfunction in STZ-Induced Diabetic Mice.","authors":"Aiqin Mao, Zicheng Li, Xiaoming Shi, Ka Zhang, Hao Kan, Li Geng, Dongxu He","doi":"10.2337/db23-0981","DOIUrl":"10.2337/db23-0981","url":null,"abstract":"<p><p>Diabetes is a significant global public health issue with implications for vascular endothelial cells (ECs) dysfunction and the subsequent development and advancement of diabetes complications. This study aims to compare the cellular and molecular properties of the aorta in normal and streptozotocin (STZ)-induced diabetic mice, with a focus on elucidating potential mechanism underlying EC dysfunction. Here, we performed a single-cell RNA sequencing survey of 32,573 cells from the aorta of normal and STZ-induced diabetic mice. We found a compendium of 10 distinct cell types, mainly ECs, smooth muscle cells, fibroblast, pericyte, immune cells, and stromal cells. As the diabetes condition progressed, we observed a subpopulation of aortic ECs that exhibited significantly elevated expression of complement (C) molecule C1qa compared with their healthy counterparts. This increased expression of C1qa was found to induce reactive oxygen species (ROS) production, facilitate EC migration and increased permeability, and impair the vasodilation within the aortic segment of mice. Furthermore, AAV-Tie2-shRNA-C1qa was administered into diabetic mice by tail vein injection, showing that inhibition of C1qa in the endothelium led to a reduction in ROS production, decreased vascular permeability, and improved vasodilation. Collectively, these findings highlight the crucial involvement of C1qa in endothelial dysfunction associated with diabetes.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1527-1536"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312588","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}