{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:18:16Z","timestamp":1788441496013,"version":"build-2803163510"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Diabetes mellitus and its complications represent a major global public health challenge, with their pathogenesis closely linked to chronic, low-grade, non-infectious metabolic inflammation. The cGAS-STING signaling pathway, a crucial innate immune sensor of cytosolic DNA, has recently emerged as a central hub linking metabolic stress to sterile inflammation. This review systematically elucidates the mechanisms and therapeutic potential of the cGAS-STING pathway in diabetes mellitus and its associated complications. Under diabetic metabolic stress conditions\u2014such as hyperglycemia and lipotoxicity\u2014mitochondrial dysfunction and nuclear DNA damage lead to the leakage of DNA into the cytoplasm, which acts as damage-associated molecular patterns (DAMPs) to activate the cGAS-STING pathway. Aberrant activation of this pathway is extensively involved in the pathogenesis of various diabetic complications, including diabetic cardiomyopathy (DCM), nephropathy, retinopathy, foot ulcers, and macrovascular disease, driving tissue damage through mechanisms such as pyroptosis, inflammatory responses, fibrosis, and cellular senescence. Furthermore, the cGAS-STING signaling cascade plays a critical role in core pathological processes of diabetes mellitus, including the regulation of insulin resistance, adipose tissue inflammation, and pancreatic \u03b2-cell dysfunction. Current intervention strategies targeting this pathway\u2014comprising small molecule inhibitors (e.g., STING inhibitors C-176\/H-151, cGAS inhibitor RU.521), strategies for mitochondrial quality control (e.g., modulating mitophagy and mitochondrial dynamics), and various natural products and traditional Chinese medicine formulations\u2014have demonstrated significant therapeutic promise in preclinical models. Nevertheless, challenges remain in this field, including cell-type specificity, therapeutic windows, pathway redundancy, and a lack of reliable biomarkers. Future directions aimed at advancing targeted therapies of the cGAS-STING pathway from bench to bedside should focus on leveraging single-cell multi-omics technologies to decipher its spatiotemporal specificity, developing precision-targeted delivery systems, exploring multi-target combination strategies, and establishing clinically applicable biomarkers. This review provides a novel perspective on the inflammatory mechanisms underlying diabetes mellitus and its complications, thereby establishing a theoretical foundation for the development of therapeutic strategies centered on modulating the cGAS-STING pathway.<\/jats:p>","DOI":"10.3389\/fphar.2026.1891745","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:52:41Z","timestamp":1788439961000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of the cGAS-STING signaling pathway in diabetes mellitus and its complications: from mechanisms to therapeutics"],"prefix":"10.3389","volume":"17","author":[{"given":"Guangdong","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Clinical Medical College, Yangzhou University","place":["Yangzhou, Jiangsu, China"]},{"name":"Department of Endocrinology, Binhai County People\u2019s Hospital","place":["Yancheng, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongxin","family":"Shang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-Innovation Center of Neuroregeneration, Medical School of Nantong University, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualin","family":"Sun","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-Innovation Center of Neuroregeneration, Medical School of Nantong University, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-Innovation Center of Neuroregeneration, Medical School of Nantong University, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanxiang","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Clinical Medical College, Yangzhou University","place":["Yangzhou, Jiangsu, China"]},{"name":"Department of Endocrinology, The First People\u2019s Hospital of Yancheng","place":["Yancheng, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"rgag056","DOI":"10.1093\/jpp\/rgag056","article-title":"Metformin as a multi-target modulator of atherosclerosis: integrated regulation of Nrf2\/KLF2, mitochondrial homeostasis, inflammation, ferroptosis, and innate immunity","volume":"78","author":"Alanazi","year":"2026","journal-title":"J. Pharm. Pharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1039\/d4md00023d","article-title":"Rosavin improves insulin resistance and alleviates hepatic and kidney damage via modulating the cGAS-STING pathway and autophagy signaling in HFD\/STZ-induced T2DM animals","volume":"15","author":"Ali","year":"2024","journal-title":"RSC Med. Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"14392","DOI":"10.1038\/ncomms14392","article-title":"IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes","volume":"8","author":"Almine","year":"2017","journal-title":"Nat. Commun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1186\/s12964-023-01393-w","article-title":"Hyperglycemia-induced STING signaling activation leads to aortic endothelial injury in diabetes","volume":"21","author":"An","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1038\/s41423-022-00919-5","article-title":"Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair","volume":"19","author":"Audu","year":"2022","journal-title":"Cell Mol. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1093\/jmcb\/mjab066","article-title":"cGAS\u2012STING signaling and function in metabolism and kidney diseases","volume":"13","author":"Bai","year":"2021","journal-title":"J. Mol. Cell Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"12196","DOI":"10.1073\/pnas.1708744114","article-title":"DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway","volume":"114","author":"Bai","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"102867","DOI":"10.1016\/j.autrev.2021.102867","article-title":"Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: potential role in Sjogren's syndrome","volume":"20","author":"Barrera","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12878-018-0104-5","article-title":"Hemostatic state augmented with platelet indices among Sudanese diabetic septic foot","volume":"18","author":"Bashir","year":"2018","journal-title":"BMC Hematology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"155933","DOI":"10.1016\/j.metabol.2024.155933","article-title":"cGAS suppresses beta-cell proliferation by a STING-independent but CEBPbeta-dependent mechanism","volume":"157","author":"Cai","year":"2024","journal-title":"Metabolism Clinical Experimental"},{"key":"B11","doi-asserted-by":"publisher","first-page":"750","DOI":"10.3390\/cimb47090750","article-title":"Targeting the cGAS-STING pathway to modulate immune inflammation in diabetes and cardiovascular complications: mechanisms and therapeutic insights","volume":"47","author":"Cai","year":"2025","journal-title":"Curr. Issues Mol. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1186\/s12915-024-02047-0","article-title":"Hoxa5 alleviates adipose tissue metabolic distortions in high-fat diet mice associated with a reduction in MERC","volume":"22","author":"Chen","year":"2024","journal-title":"BMC Biology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s10753-024-02058-7","article-title":"BRG1 deficiency promotes cardiomyocyte inflammation and apoptosis by activating the cGAS-STING signaling in diabetic cardiomyopathy","volume":"48","author":"Chen","year":"","journal-title":"Inflammation"},{"key":"B14","doi-asserted-by":"publisher","first-page":"170675","DOI":"10.1016\/j.cej.2025.170675","article-title":"Dual-network hydrogel loaded with octreotide promotes diabetic wound healing by inhibiting cGAS-STING pathway","volume":"526","author":"Chen","year":"","journal-title":"Chem. Eng. J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e70657","DOI":"10.1111\/cns.70657","article-title":"AMPK\/SIRT1\/PGC-1alpha signaling pathway: molecular mechanisms and targeted strategies from energy homeostasis regulation to disease therapy","volume":"31","author":"Chen","year":"","journal-title":"CNS Neuroscience and Therapeutics"},{"key":"B16","doi-asserted-by":"publisher","first-page":"115968","DOI":"10.1016\/j.intimp.2025.115968","article-title":"Endoplasmic reticulum stress orchestrates cGAS-STING activation in lipid metabolism-associated disorders","volume":"169","author":"Chen","year":"","journal-title":"Int. Immunopharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"118218","DOI":"10.1016\/j.bcp.2026.118218","article-title":"The central role of endoplasmic reticulum stress in Parkinson's disease and targeted therapeutic strategies","volume":"252","author":"Chen","year":"","journal-title":"Biochem. Pharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1016\/j.cmet.2019.08.003","article-title":"Mitochondrial damage and activation of the STING pathway lead to renal inflammation and fibrosis","volume":"30","author":"Chung","year":"2019","journal-title":"Cell Metab."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1344276","DOI":"10.3389\/fphar.2024.1344276","article-title":"Celecoxib ameliorates diabetic sarcopenia by inhibiting inflammation, stress response, mitochondrial dysfunction, and subsequent activation of the protein degradation systems","volume":"15","author":"Deng","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"958","DOI":"10.2337\/db22-0654","article-title":"Regulation of monocyte activation by PPARalpha through interaction with the cGAS-STING pathway","volume":"72","author":"Dong","year":"2023","journal-title":"Diabetes"},{"key":"B21","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3390\/healthcare13010046","article-title":"The mediating role of general self-efficacy in health self-management and psychological stress among older adults in shanghai: a structural equation modeling analysis","volume":"13","author":"Du","year":"2024","journal-title":"Healthc. (Basel)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/jb\/mvag017","article-title":"Innate immune signalling in the adipocyte","volume":"179","author":"Dumesic","year":"2026","journal-title":"J. Biochem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1016\/j.cmet.2025.01.013","article-title":"RBM43 controls PGC1alpha translation and a PGC1alpha-STING signaling axis","volume":"37","author":"Dumesic","year":"2025","journal-title":"Cell Metab."},{"key":"B24","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13098-025-01600-3","article-title":"ZBiotics ameliorates T2DM-induced histopathological damage in liver, kidney and adipose tissues by modulating the NOD-like receptor signaling in Wistar rats","volume":"17","author":"Esawie","year":"2025","journal-title":"Diabetol. Metab. Syndr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"114252","DOI":"10.4239\/wjd.v17.i2.114252","article-title":"Electroacupuncture protects gastric Cajal cells by reducing macrophage pyroptosis in diabetic gastroparesis","volume":"17","author":"Fan","year":"2026","journal-title":"World J. Diabetes"},{"key":"B26","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.bbrc.2022.04.085","article-title":"STING activation promotes inflammatory response and delays skin wound healing in diabetic mice","volume":"611","author":"Feng","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e23127","DOI":"10.1096\/fj.202300342rrr","article-title":"PCSK9 causes inflammation and cGAS\/STING pathway activation in diabetic nephropathy","volume":"37","author":"Feng","year":"2023","journal-title":"FASEB J."},{"key":"B28","doi-asserted-by":"publisher","first-page":"178266","DOI":"10.1016\/j.ejphar.2025.178266","article-title":"Amlexanox alleviates renal inflammation and fibrosis by inhibiting cGAS\/STING\/TBK1 and TGF-beta1\/Smad signaling","volume":"1007","author":"Gairola","year":"2025","journal-title":"Eur. Journal Pharmacology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"115190","DOI":"10.1016\/j.intimp.2025.115190","article-title":"A novel GPR84 antagonist attenuates diabetic lung injury by inhibiting pyroptosis via the cGAS-STING pathway in pulmonary vascular endothelial cells","volume":"163","author":"Gao","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"7281","DOI":"10.3390\/ijms22147281","article-title":"Nuclear envelope integrity in health and disease: consequences on genome instability and inflammation","volume":"22","author":"Gauthier","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3010","DOI":"10.21037\/tlcr-24-649","article-title":"STING facilitates the development of radiation-induced lung injury via regulating the PERK\/eIF2alpha pathway","volume":"13","author":"Ge","year":"2024","journal-title":"Transl. Lung Cancer Research"},{"key":"B32","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s12974-025-03391-w","article-title":"cGAMP promotes inner blood-retinal barrier breakdown through P2RX7-mediated transportation into microglia","volume":"22","author":"Ge","year":"2025","journal-title":"J. Neuroinflammation"},{"key":"B33","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/s41420-023-01425-x","article-title":"High glucose-induced STING activation inhibits diabetic wound healing through promoting M1 polarization of macrophages","volume":"9","author":"Geng","year":"2023","journal-title":"Cell Death Discov."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1729941","DOI":"10.3389\/fphar.2025.1729941","article-title":"Molecular mechanisms and multi-target therapeutic strategies of diabetic nephropathy: from pathogenesis to precision interventions","volume":"16","author":"Gong","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"179208","DOI":"10.1016\/j.ejphar.2026.179208","article-title":"The dual role of cell death in skeletal muscle homeostasis and disease: mechanisms and therapeutic targeting","volume":"1031","author":"Gong","year":"2026","journal-title":"Eur. Journal Pharmacology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s00018-026-06161-w","article-title":"Fibroblast growth factor-inducible 14 accelerates pulmonary fibrosis by inducing fibroblast senescence in mice","volume":"83","author":"Guan","year":"2026","journal-title":"Cell. Mol. Life Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"157399","DOI":"10.1016\/j.phymed.2025.157399","article-title":"Qihuang Yishen formula attenuates renal tubular injury by modulating inflammation via the cGAS\/STING pathway in diabetic kidney disease","volume":"148","author":"Guo","year":"2025","journal-title":"Phytomedicine"},{"key":"B38","doi-asserted-by":"publisher","first-page":"103733","DOI":"10.1016\/j.tice.2026.103733","article-title":"Interrupting a mitochondrial DNA-driven innate immune circuit attenuates hepatic tissue remodeling and fibrotic architecture in experimental steatohepatitis","volume":"103","author":"Hamad","year":"2026","journal-title":"Tissue and Cell"},{"key":"B39","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12979-020-00176-y","article-title":"First evidence for STING SNP R293Q being protective regarding obesity-associated cardiovascular disease in age-advanced subjects - a cohort study","volume":"17","author":"Hamann","year":"2020","journal-title":"Immun. Ageing"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e2300230","DOI":"10.1002\/smtd.202300230","article-title":"Triple tumor microenvironment-responsive ferroptosis pathways induced by manganese-based imageable nanoenzymes for enhanced breast cancer theranostics","volume":"7","author":"He","year":"2023","journal-title":"Small Methods"},{"key":"B41","doi-asserted-by":"publisher","first-page":"tkad050","DOI":"10.1093\/burnst\/tkad050","article-title":"The cGAS-STING pathway: a therapeutic target in diabetes and its complications","volume":"12","author":"He","year":"","journal-title":"Burns and Trauma"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2613","DOI":"10.1016\/j.apsb.2024.03.011","article-title":"Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling","volume":"14","author":"He","year":"","journal-title":"Acta Pharmaceutica Sin. B"},{"key":"B43","doi-asserted-by":"publisher","first-page":"e2410910","DOI":"10.1002\/advs.202410910","article-title":"Microglial cGAS deletion preserves intercellular communication and alleviates amyloid-beta-induced pathogenesis of Alzheimer's disease","volume":"12","author":"He","year":"2025","journal-title":"Adv. Sci. (Weinh)"},{"key":"B44","doi-asserted-by":"publisher","first-page":"108658","DOI":"10.1016\/j.intimp.2022.108658","article-title":"The selective STING inhibitor H-151 preserves myocardial function and ameliorates cardiac fibrosis in murine myocardial infarction","volume":"107","author":"Hu","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.34133\/research.1042","article-title":"Apoptotic vesicle membrane-mediated targeted endothelial mitochondrial transplantation-clearance therapy for diabetic wound healing","volume":"9","author":"Hu","year":"2026","journal-title":"Research"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e70337","DOI":"10.1002\/ctm2.70337","article-title":"Elevation of ISG15 promotes diabetic kidney disease by modulating renal tubular epithelial cell pyroptosis","volume":"15","author":"Huang","year":"","journal-title":"Clin. Transl. Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1186\/s12967-024-05250-3","article-title":"IL-37 ameliorates myocardial fibrosis by regulating mtDNA-enriched vesicle release in diabetic cardiomyopathy mice","volume":"22","author":"Huang","year":"2024","journal-title":"J. Transl. Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41419-025-07379-5","article-title":"Endurance exercise remodels skeletal muscle by suppressing Ythdf1-mediated myostatin expression","volume":"16","author":"Huang","year":"","journal-title":"Cell Death and Disease"},{"key":"B49","doi-asserted-by":"publisher","first-page":"116799","DOI":"10.1016\/j.bcp.2025.116799","article-title":"Endoplasmic reticulum stress and unfolded protein response: roles in skeletal muscle atrophy","volume":"234","author":"Ji","year":"2025","journal-title":"Biochem. Pharmacology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"117854","DOI":"10.1016\/j.bcp.2026.117854","article-title":"The cGAS-STING signaling pathway: a central regulator and novel therapeutic target in skeletal muscle pathophysiology","volume":"248","author":"Jiang","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"14391","DOI":"10.1038\/ncomms14391","article-title":"IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP","volume":"8","author":"Jonsson","year":"2017","journal-title":"Nat. Commun."},{"key":"B52","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1038\/s41586-025-09536-4","article-title":"STING induces ZBP1-mediated necroptosis independently of TNFR1 and FADD","volume":"647","author":"Kelepouras","year":"2025","journal-title":"Nature"},{"key":"B53","doi-asserted-by":"publisher","first-page":"e174126","DOI":"10.1172\/jci.insight.174126","article-title":"Role of cGAS\/STING pathway in aging and sexual dimorphism in diabetic kidney disease","volume":"10","author":"Khedr","year":"2024","journal-title":"JCI Insight"},{"key":"B54","doi-asserted-by":"publisher","first-page":"108335","DOI":"10.1016\/j.mrrev.2020.108335","article-title":"Micronuclei, inflammation and auto-immune disease","volume":"786","author":"Kirsch-Volders","year":"2020","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"e13382","DOI":"10.1111\/imr.13382","article-title":"DNA sensors in metabolic and cardiovascular diseases: molecular mechanisms and therapeutic prospects","volume":"329","author":"Kwak","year":"2025","journal-title":"Immunol. Rev."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1644289","DOI":"10.3389\/fimmu.2025.1644289","article-title":"Macrophage PTP1B regulates mitochondrial dynamics via the JAK2\/STAT3-OPA1 axis and activates the cGAS\/STING signaling pathway","volume":"16","author":"Lei","year":"2025","journal-title":"Front. Immunol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41419-023-06111-5","article-title":"TGR5 supresses cGAS\/STING pathway by inhibiting GRP75-mediated endoplasmic reticulum-mitochondrial coupling in diabetic retinopathy","volume":"14","author":"Li","year":"2023","journal-title":"Cell Death Dis."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e70130","DOI":"10.1111\/jcmm.70130","article-title":"PLAGL1 overexpression induces cytoplasmic DNA accumulation that triggers cGAS\/STING activation","volume":"28","author":"Li","year":"","journal-title":"J. Cell Mol. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1457369","DOI":"10.3389\/fcell.2024.1457369","article-title":"DNA damage-induced AIM2 pyroptosis in high glucose-induced proximal tubular epithelial cell","volume":"12","author":"Li","year":"","journal-title":"Front. Cell Dev. Biol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/jdi.70204","article-title":"PLAGL1 overexpression exacerbates type 1 diabetes by inducing beta-cell apoptosis via oxidative stress-dependent dual DNA damage and cGAS\/STING pathway activation","volume":"17","author":"Li","year":"","journal-title":"J. Diabetes Investig."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.3390\/ph19071091","article-title":"Mechanisms of impaired skeletal muscle regeneration and therapeutic approaches in aging and chronic disease","volume":"19","author":"Li","year":"","journal-title":"Pharm. (Basel)"},{"key":"B62","doi-asserted-by":"publisher","first-page":"9621","DOI":"10.1038\/s41467-024-53798-x","article-title":"TET2 germline variants promote kidney disease by impairing DNA repair and activating cytosolic nucleotide sensors","volume":"15","author":"Liang","year":"2024","journal-title":"Nat. Commun."},{"key":"B63","doi-asserted-by":"publisher","first-page":"e168945","DOI":"10.1172\/jci.insight.168945","article-title":"Activated cGAS\/STING signaling elicits endothelial cell senescence in early diabetic retinopathy","volume":"8","author":"Liu","year":"2023","journal-title":"JCI Insight"},{"key":"B64","doi-asserted-by":"publisher","first-page":"118031","DOI":"10.1016\/j.bcp.2026.118031","article-title":"Mechanisms and therapeutic potential of the cGAS-STING signaling pathway in macrophage activation and polarization","volume":"250","author":"Liu","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.jare.2022.10.014","article-title":"Metrnl ameliorates diabetic cardiomyopathy via inactivation of cGAS\/STING signaling dependent on LKB1\/AMPK\/ULK1-mediated autophagy","volume":"51","author":"Lu","year":"2023","journal-title":"J. Adv. Res."},{"key":"B66","doi-asserted-by":"publisher","first-page":"e70882","DOI":"10.1111\/jcmm.70882","article-title":"Jiangtang Tiaozhi formula relieves HFD-induced obesity related type 2 diabetes by inhibiting the cGAS-STING pathway","volume":"29","author":"Luo","year":"2025","journal-title":"J. Cell Mol. Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s10565-021-09692-z","article-title":"Lipotoxicity-induced mtDNA release promotes diabetic cardiomyopathy by activating the cGAS-STING pathway in obesity-related diabetes","volume":"39","author":"Ma","year":"","journal-title":"Cell Biol. Toxicol."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.26402\/jpp.2023.6.04","article-title":"Orphan nuclear receptor 4 A1 involvement in transforming growth factor beta1-induced myocardial fibrosis in diabetic mice","volume":"74","author":"Ma","year":"","journal-title":"J. Physiol. Pharmacol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1002\/hep.32604","article-title":"Loss of hepatic DRP1 exacerbates alcoholic hepatitis by inducing megamitochondria and mitochondrial maladaptation","volume":"77","author":"Ma","year":"","journal-title":"Hepatology"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.3390\/biom15091223","article-title":"Beneficial effects of different types of exercise on diabetic cardiomyopathy","volume":"15","author":"Ma","year":"2025","journal-title":"Biomolecules"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-026-01699-5","article-title":"Cortistatin antagonizes Piezo1-STING axis and facilitates mitochondrial homeostasis of keratinocytes by attenuating AGEs accumulation in diabetic ulcers","author":"Ma","year":"2026","journal-title":"Cell Death Differentiation"},{"key":"B72","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1161\/ATVBAHA.117.309017","article-title":"STING-IRF3 triggers endothelial inflammation in response to free fatty acid-induced mitochondrial damage in diet-induced obesity","volume":"37","author":"Mao","year":"2017","journal-title":"Arteriosclerosis, Thrombosis, Vascular Biology"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.7150\/thno.124140","article-title":"Impairment of mitochondrial quality control exacerbates diabetes-related atrial fibrillation by cGAS-STING signaling pathway and cardiomyocyte-macrophage crosstalk","volume":"16","author":"Meng","year":"2026","journal-title":"Theranostics"},{"key":"B74","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.1681\/asn.2021101286","article-title":"Activation of stimulator of IFN genes (STING) causes proteinuria and contributes to glomerular diseases","volume":"33","author":"Mitrofanova","year":"2022","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"B75","doi-asserted-by":"publisher","first-page":"343","DOI":"10.23736\/S0031-0808.20.03937-3","article-title":"Protein kinase TBK1\/IKKepsilon inhibitor Amlexanox improves cardiac function after acute myocardial infarction in rats","volume":"65","author":"Mo","year":"2023","journal-title":"Panminerva Medica"},{"key":"B76","doi-asserted-by":"publisher","first-page":"134210","DOI":"10.1016\/j.ijbiomac.2024.134210","article-title":"Implications of the cGAS-STING pathway in diabetes: risk factors and therapeutic strategies","volume":"278","author":"Mohammadi","year":"2024","journal-title":"Int. Journal Biological Macromolecules"},{"key":"B77","doi-asserted-by":"publisher","first-page":"104975","DOI":"10.1016\/j.jbc.2023.104975","article-title":"NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease","volume":"299","author":"Myakala","year":"2023","journal-title":"J. Biol. Chem."},{"key":"B78","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.2337\/db24-0686","article-title":"Application of dental pulp stem cell-derived intracellular vesicles for diabetic wound healing","volume":"74","author":"Pang","year":"2025","journal-title":"Diabetes"},{"key":"B79","doi-asserted-by":"publisher","first-page":"6217","DOI":"10.1007\/s12035-024-03933-y","article-title":"Experimental type 2 diabetes and lipotoxicity-associated neuroinflammation involve mitochondrial DNA-mediated cGAS\/STING axis: implication of Type-1 interferon response in cognitive impairment","volume":"61","author":"Preeti","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"117999","DOI":"10.1016\/j.bcp.2026.117999","article-title":"Network of cell death in myocardial ischemia-reperfusion injury: mechanisms and targeted therapeutic strategies","volume":"250","author":"Qi","year":"","journal-title":"Biochem. Pharmacol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"117704","DOI":"10.1016\/j.bcp.2026.117704","article-title":"The myocardial ischemic cascade network and multi-target synergistic interventions: from molecular mechanisms to therapeutic innovations","volume":"246","author":"Qi","year":"","journal-title":"Biochem. Pharmacol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1007\/s00125-025-06628-8","article-title":"Aberrant STING signalling promotes endothelial dysfunction and neurovascular injury in diabetic retinopathy","volume":"69","author":"Qin","year":"2026","journal-title":"Diabetologia"},{"key":"B83","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s13205-025-04516-x","article-title":"Tao Hong Si Wu decoction attenuates myocardial injury in diabetic mice by regulating the cGAS\/STING\/NLRP3 axis","volume":"15","author":"Shen","year":"2025","journal-title":"3 Biotech."},{"key":"B84","doi-asserted-by":"publisher","first-page":"110856","DOI":"10.1016\/j.celrep.2022.110856","article-title":"DDX41 is required for cGAS-STING activation against DNA virus infection","volume":"39","author":"Singh","year":"2022","journal-title":"Cell Rep."},{"key":"B85","doi-asserted-by":"publisher","first-page":"274","DOI":"10.31083\/j.fbl2907274","article-title":"LARP7 contributes to glucose-induced cardiac dysfunction, apoptosis and fibrosis by inhibiting the degradation of STING","volume":"29","author":"Sun","year":"2024","journal-title":"Front. Biosci. Landmark Ed."},{"key":"B86","doi-asserted-by":"publisher","first-page":"1689522","DOI":"10.3389\/fphar.2025.1689522","article-title":"Diabetes mellitus-driven pulmonary injury: multidimensional mechanisms linking metabolic dysregulation to gut-lung axis and promising therapies","volume":"16","author":"Sun","year":"","journal-title":"Front. Pharmacol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.freeradbiomed.2025.05.383","article-title":"Fenofibrate inhibits activation of cGAS-STING pathway by alleviating mitochondrial damage to attenuate inflammatory response in diabetic dry eye","volume":"235","author":"Sun","year":"","journal-title":"Free Radical Biology and Medicine"},{"key":"B88","doi-asserted-by":"publisher","first-page":"117545","DOI":"10.1016\/j.bcp.2025.117545","article-title":"Tectorigenin alleviates diabetic lung injury by restoring gut microbiota and metabolic homeostasis","volume":"243","author":"Sun","year":"2026","journal-title":"Biochem. Pharmacology"},{"key":"B89","doi-asserted-by":"publisher","first-page":"1674018","DOI":"10.3389\/fimmu.2025.1674018","article-title":"Exploring the pathogenesis of MAFLD from an immunological perspective: from the perspective of the cGAS\/STING\/NF-kappaB signaling pathway","volume":"16","author":"Tian","year":"2025","journal-title":"Front. Immunol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1681\/asn.0000000000000428","article-title":"METTL3-Mediated N 6 -Methyladenosine mRNA modification and cGAS-STING pathway activity in kidney fibrosis","volume":"35","author":"Tsai","year":"2024","journal-title":"J. Am. Soc. Nephrol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated TCA cycle proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Sci. (New York, NY)"},{"key":"B92","doi-asserted-by":"publisher","first-page":"eadd8564","DOI":"10.1126\/sciadv.add8564","article-title":"Synthetic enforcement of STING signaling in cancer cells appropriates the immune microenvironment for checkpoint inhibitor therapy","volume":"9","author":"Vornholz","year":"2023","journal-title":"Sci. Adv."},{"key":"B93","doi-asserted-by":"publisher","first-page":"e70127","DOI":"10.1096\/fj.202401299rr","article-title":"Homoplantaginin alleviates high glucose-induced vascular endothelial senescence by inhibiting mtDNA-cGAS-STING pathway via blunting DRP1-mitochondrial fission-VDAC1 axis","volume":"38","author":"Wang","year":"","journal-title":"FASEB J."},{"key":"B94","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s12974-024-03072-0","article-title":"Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson's disease through Mfn2-cGAS signaling","volume":"21","author":"Wang","year":"","journal-title":"J. Neuroinflammation"},{"key":"B95","doi-asserted-by":"publisher","first-page":"102119","DOI":"10.1016\/j.mtbio.2025.102119","article-title":"AhR deficiency exacerbates inflammation in diabetic wounds via impaired mitophagy and cGAS-STING-NLRP3 activation: therapeutic potential of hydrogels loaded with FICZ","volume":"34","author":"Wang","year":"","journal-title":"Mater. Today Bio"},{"key":"B96","doi-asserted-by":"publisher","first-page":"6035","DOI":"10.1111\/febs.17421","article-title":"FXR suppress Muller cell activation by regulating cGAS\/STING pathway in diabetic retinopathy","volume":"292","author":"Wang","year":"","journal-title":"FEBS J."},{"key":"B97","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.3390\/ph19071056","article-title":"The central role of the AMPK\/SIRT1\/PGC-1alpha signaling axis in skeletal muscle physiology and pathology and its targeted therapeutic strategies","volume":"19","author":"Wang","year":"","journal-title":"Pharm. (Basel)"},{"key":"B98","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s13105-026-01170-6","article-title":"Luteolin ameliorates diabetic retinopathy through activation of the Nrf2\/Keap1 and SIRT3\/AMPK antioxidant axes and suppression of cGAS-STING and Wnt\/beta-catenin pathways in experimental rats","volume":"82","author":"Wang","year":"","journal-title":"J. Physiol. Biochem."},{"key":"B99","doi-asserted-by":"publisher","first-page":"118317","DOI":"10.1016\/j.bcp.2026.118317","article-title":"The role and mechanisms of the cGAS-STING signaling pathway in age-related pathophysiological processes: challenges and therapeutic strategies","volume":"253","author":"Wei","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.7150\/ijbs.85562","article-title":"Ubiquitin specific protease 38 aggravates pathological cardiac remodeling by stabilizing phospho-TBK1","volume":"20","author":"Xiao","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"B101","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s12964-023-01216-y","article-title":"Decreased MFN2 activates the cGAS-STING pathway in diabetic myocardial ischaemia-reperfusion by triggering the release of mitochondrial DNA","volume":"21","author":"Xiong","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"B102","doi-asserted-by":"publisher","first-page":"158182","DOI":"10.1016\/j.phymed.2026.158182","article-title":"Sesamin ameliorates high-fat diet-induced inflammation and metabolic dysfunction in pregnant uterine smooth muscle via cGAS-STING inhibition","volume":"156","author":"Xu","year":"2026","journal-title":"Phytomedicine"},{"key":"B103","doi-asserted-by":"publisher","first-page":"118219","DOI":"10.1016\/j.bcp.2026.118219","article-title":"The role of Piezo1 in skeletal muscle physiology and pathology: from mechanosensing to precision therapy","volume":"252","author":"Xue","year":"2026","journal-title":"Biochem. Pharmacology"},{"key":"B104","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/s41420-022-01046-w","article-title":"Mitochondrial damage and activation of the cytosolic DNA sensor cGAS-STING pathway lead to cardiac pyroptosis and hypertrophy in diabetic cardiomyopathy mice","volume":"8","author":"Yan","year":"2022","journal-title":"Cell Death Discov."},{"key":"B105","doi-asserted-by":"publisher","first-page":"114963","DOI":"10.1016\/j.colsurfb.2025.114963","article-title":"Oxygen-boosted nanodrug for amplified ferroptosis-photodynamic immunotherapy together with PD-1 checkpoint blockade against triple-negative breast cancer","volume":"255","author":"Yang","year":"2025","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"B106","doi-asserted-by":"publisher","first-page":"1810417","DOI":"10.3389\/fphar.2026.1810417","article-title":"The dual pathological roles and targeted therapy of PGE(2): from receptor signaling networks to disease microenvironment modulation","volume":"17","author":"Yang","year":"2026","journal-title":"Front. Pharmacol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"4030","DOI":"10.1016\/j.apsb.2025.06.014","article-title":"Targeted inhibition of macrophage STING signaling alleviates inflammatory injury and ventricular remodeling in acute myocardial infarction","volume":"15","author":"Yao","year":"2025","journal-title":"Acta Pharmaceutica Sin. B"},{"key":"B108","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12929-024-01039-0","article-title":"Excess glucose alone depress young mesenchymal stromal\/stem cell osteogenesis and mitochondria activity within hours\/days via NAD(+)\/SIRT1 axis","volume":"31","author":"Yen","year":"2024","journal-title":"J. Biomed. Sci."},{"key":"B109","doi-asserted-by":"publisher","first-page":"117627","DOI":"10.1016\/j.bcp.2025.117627","article-title":"RIPK3 deficiency ameliorates diabetic sarcopenia through proteostasis regulation by suppressing inflammatory signaling and cellular stress pathways","volume":"244","author":"Yi","year":"2026","journal-title":"Biochem. Pharmacology"},{"key":"B110","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.bioactmat.2026.04.009","article-title":"Polysaccharide-engineered mitochondria reprogram macrophages to resolve diabetic wound inflammation and promote repair","volume":"63","author":"Yu","year":"2026","journal-title":"Bioact. Materials"},{"key":"B111","doi-asserted-by":"publisher","first-page":"15002","DOI":"10.1074\/jbc.M117.804005","article-title":"Palmitic acid dysregulates the Hippo-YAP pathway and inhibits angiogenesis by inducing mitochondrial damage and activating the cytosolic DNA sensor cGAS-STING-IRF3 signaling mechanism","volume":"292","author":"Yuan","year":"2017","journal-title":"J. Biol. Chem."},{"key":"B112","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s11255-025-04651-7","article-title":"Targeting the TFAM-cGAS-STING axis: a mitochondrial-inflammatory link in the pathogenesis and treatment of diabetic kidney disease","volume":"58","author":"Yun","year":"2026","journal-title":"Int. Urology Nephrology"},{"key":"B113","doi-asserted-by":"publisher","first-page":"105145","DOI":"10.1016\/j.isci.2022.105145","article-title":"cGAS-STING activation contributes to podocyte injury in diabetic kidney disease","volume":"25","author":"Zang","year":"2022","journal-title":"iScience"},{"key":"B114","doi-asserted-by":"publisher","first-page":"4519","DOI":"10.1016\/j.molcel.2022.10.026","article-title":"AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity","volume":"82","author":"Zhang","year":"2022","journal-title":"Mol. Cell"},{"key":"B115","doi-asserted-by":"publisher","first-page":"111805","DOI":"10.1016\/j.cellsig.2025.111805","article-title":"Leptin attenuates diabetic cardiomyopathy-induced cardiac remodeling via regulating cGAS\/STING signaling and Opa1-mediated mitochondrial fusion","volume":"132","author":"Zhang","year":"","journal-title":"Cell Signal"},{"key":"B116","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12872-025-04543-9","article-title":"U-shaped association between plasma cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) levels and myocardial infarction","volume":"25","author":"Zhang","year":"","journal-title":"BMC Cardiovascular Disorders"},{"key":"B117","doi-asserted-by":"publisher","first-page":"225","DOI":"10.4103\/apjtb.apjtb_58_26","article-title":"Isorhamnetin attenuates diabetic kidney disease by modulating mitochondrial homeostasis and suppressing cGAS-STING axis-dependent NLRP3 inflammasome activation","volume":"16","author":"Zhang","year":"2026","journal-title":"Asian Pac J. Trop. bio."},{"key":"B118","doi-asserted-by":"publisher","first-page":"233","DOI":"10.2337\/db21-0173","article-title":"GRP75 regulates mitochondrial-supercomplex turnover to modulate insulin sensitivity","volume":"71","author":"Zhao","year":"","journal-title":"Diabetes"},{"key":"B119","doi-asserted-by":"publisher","first-page":"e155552","DOI":"10.1172\/jci.insight.155552","article-title":"The TBK1\/IKKepsilon inhibitor amlexanox improves dyslipidemia and prevents atherosclerosis","volume":"7","author":"Zhao","year":"","journal-title":"JCI Insight"},{"key":"B120","doi-asserted-by":"publisher","first-page":"4985","DOI":"10.1007\/s00415-022-11146-3","article-title":"Circulating cell-free mtDNA release is associated with the activation of cGAS-STING pathway and inflammation in mitochondrial diseases","volume":"269","author":"Zhao","year":"","journal-title":"J. Neurol."},{"key":"B121","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.freeradbiomed.2024.12.016","article-title":"Spermidine alleviates diabetic periodontitis by reversing human periodontal ligament stem cell senescence via mitophagy","volume":"227","author":"Zhou","year":"2025","journal-title":"Free Radical Biology and Medicine"},{"key":"B122","doi-asserted-by":"publisher","first-page":"e71540","DOI":"10.1096\/fj.202503913r","article-title":"Cardiomyocyte-derived USP20 attenuates diabetic cardiomyopathy by facilitating the degradation of STING and mitigating STING-mediated inflammation","volume":"40","author":"Zhou","year":"2026","journal-title":"FASEB Journal"},{"key":"B123","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1038\/s41467-025-56891-x","article-title":"CerS6 links ceramide metabolism to innate immune responses in diabetic kidney disease","volume":"16","author":"Zhu","year":"2025","journal-title":"Nat. Communications"},{"key":"B124","doi-asserted-by":"publisher","first-page":"111971","DOI":"10.1016\/j.intimp.2024.111971","article-title":"Salvianolic acid A prevents UV-induced skin damage by inhibiting the cGAS-STING pathway","volume":"132","author":"Zuo","year":"2024","journal-title":"Int. Immunopharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1891745\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:52:43Z","timestamp":1788439963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1891745\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":124,"alternative-id":["10.3389\/fphar.2026.1891745"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1891745","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1891745"}}