{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:35:39Z","timestamp":1789011339270,"version":"build-2803163510"},"reference-count":129,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Veterinary Medicine and Animal Science, Poznan University of Life Sciences, Poland","award":["506.558.04.00"],"award-info":[{"award-number":["506.558.04.00"]}]},{"name":"Department of Animal Physiology, Biochemistry, and Biostructure","award":["506.558.04.00"],"award-info":[{"award-number":["506.558.04.00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Quercetin is a biologically active flavonoid compound that exerts numerous beneficial effects in humans and animals, including anti-diabetic activity. Its action has been explored in rodent models of type 1 and type 2 diabetes. It was revealed that quercetin mitigated diabetes-related hormonal and metabolic disorders and reduced oxidative and inflammatory stress. Its anti-diabetic effects were associated with advantageous changes in the relevant enzymes and signaling molecules. Quercetin positively affected, among others, superoxide dismutase, catalase, glutathione peroxidase, glucose transporter-2, glucokinase, glucose-6-phosphatase, glycogen phosphorylase, glycogen synthase, glycogen synthase kinase-3\u03b2, phosphoenolpyruvate carboxykinase, silent information regulator-1, sterol regulatory element-binding protein-1, insulin receptor substrate 1, phosphoinositide 3-kinase, and protein kinase B. The available data support the conclusion that the action of quercetin was pleiotropic since it alleviates a wide range of diabetes-related disorders. Moreover, no side effects were observed during treatment with quercetin in rodents. Given that human diabetes affects a large part of the population worldwide, the results of animal studies encourage clinical trials to evaluate the potential of quercetin as an adjunct to pharmacological therapies.<\/jats:p>","DOI":"10.3390\/ijms26157391","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T15:56:16Z","timestamp":1754409376000},"page":"7391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Quercetin as an Anti-Diabetic Agent in Rodents\u2014Is It Worth Testing in Humans?"],"prefix":"10.3390","volume":"26","author":[{"given":"Tomasz","family":"Szkudelski","sequence":"first","affiliation":[{"name":"Department of Animal Physiology, Biochemistry and Biostructure, Pozna\u0144 University of Life Sciences, Wo\u0142y\u0144ska 35, 60-637 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6828-0534","authenticated-orcid":false,"given":"Katarzyna","family":"Szkudelska","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, Biochemistry and Biostructure, Pozna\u0144 University of Life Sciences, Wo\u0142y\u0144ska 35, 60-637 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3827-2282","authenticated-orcid":false,"given":"Aleksandra","family":"\u0141angowska","sequence":"additional","affiliation":[{"name":"Department of Zoology, Pozna\u0144 University of Life Sciences, Wojska Polskiego 71C, 60-625 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"and Maurya, P.K. (2022). Health Benefits of Quercetin in Age-Related Diseases. Molecules, 27.","DOI":"10.3390\/molecules27082498"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Baqer, S.H., Al-Shawi, S.G., and Al-Younis, Z.K. (2024). Quercetin, the potential powerful flavonoid for human and food: A review. Front. Biosci. (Elite Ed.), 16.","DOI":"10.31083\/j.fbe1603030"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Alharbi, H.O.A., Alshebremi, M., Babiker, A.Y., and Rahmani, A.H. (2025). The role of quercetin, a flavonoid in the management of pathogenesis through regulation of oxidative stress, inflammation, and biological activities. Biomolecules, 15.","DOI":"10.3390\/biom15010151"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rana, J.N., and Mumtaz, S. (2025). Prunin: An emerging anticancer flavonoid. Int. J. Mol. Sci., 16.","DOI":"10.3390\/ijms26062678"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zahra, M., Abrahamse, H., and George, B.P. (2024). Flavonoids: Antioxidant powerhouses and their role in nanomedicine. Antioxidants, 29.","DOI":"10.3390\/antiox13080922"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.2174\/0929867330666230207112539","article-title":"Berberine: Pharmacological features in health, disease and aging","volume":"31","author":"Gasmi","year":"2024","journal-title":"Curr. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2174\/1389450123666220915121236","article-title":"An insight into diverse activities and targets of flavonoids","volume":"24","author":"Tiwari","year":"2023","journal-title":"Curr. Drug Targets"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pan, Y., Matsunaga, T., Zhang, T., and Akaike, T. (2025). The therapeutic potential of supersulfides in oxidative stress-related diseases. Biomolecules, 15.","DOI":"10.3390\/biom15020172"},{"key":"ref_9","unstructured":"(2025, February 10). American Diabetes Association. Available online: https:\/\/www.diabetes.org\/."},{"key":"ref_10","unstructured":"International Diabetes Federation (2025). Diabetes Atlas, International Diabetes Federation. [11th ed.]. Available online: https:\/\/diabetesatlas.org\/resources\/idf-diabetes-atlas-2025\/."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Patel, S., and Remedi, M.S. (2024). Loss of \u03b2-cell identity and dedifferentiation, not an irreversible process?. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1414447"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4093\/dmj.2024.0796","article-title":"Overcoming beta-cell dysfunction in type 2 diabetes mellitus: CD36 inhibition and antioxidant system","volume":"49","author":"Park","year":"2025","journal-title":"Diabetes Metab. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/157488631601210203093615","article-title":"Diabetes and its complications\u2014Contemporary treatment and potential side effects of drugs to treat diabetes","volume":"16","author":"Vestergaard","year":"2021","journal-title":"Curr. Drug Saf."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Padhi, S., Nayak, A.K., and Behera, A. (2020). Type II diabetes mellitus: A review on recent drug-based therapeutics. Biomed. Pharmacother., 131.","DOI":"10.1016\/j.biopha.2020.110708"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1080\/10408398.2018.1492900","article-title":"Dietary polyphenols and type 2 diabetes: Human study and clinical trial","volume":"59","author":"Cao","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Szkudelska, K., and Szkudelski, T. (2022). The anti-diabetic potential of betaine: Mechanisms of action in rodent models of type 2 diabetes. Biomed. Pharmacother., 150.","DOI":"10.1016\/j.biopha.2022.112946"},{"key":"ref_17","first-page":"1","article-title":"Herbal approaches to diabetes management: Pharmacological mechanisms and omics-driven discoveries","volume":"17","author":"Roy","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Guerrero-Becerra, L., Morimoto, S., Arrellano-Ordo\u00f1ez, E., Morales-Miranda, A., Guevara-Gonzalez, R.G., Feregrino-P\u00e9rez, A.A., and Lomas-Soria, C. (2025). Polyphenolic compounds in fabaceous plants with antidiabetic potential. Pharmaceuticals, 18.","DOI":"10.3390\/ph18010069"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5641","DOI":"10.1002\/ptr.8332","article-title":"Unraveling quercetin\u2019s potential: A comprehensive review of its properties and mechanisms of action in diabetes and obesity complications","volume":"38","author":"Yi","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mustafa, N.H., Siti, H.N., and Kamisah, Y. (2024). Role of quercetin in diabetic cardiomyopathy. Plants, 14.","DOI":"10.3390\/plants14010025"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hossein, A., Firouzeh, G., Zeinab, K., and Gholamreza, D. (2024). Quercetin prevents kidney against diabetes mellitus (type 1) in rats by inhibiting TGF-beta\/apelin gene expression. Mol. Biol. Rep., 51.","DOI":"10.1007\/s11033-024-09617-z"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2327495","DOI":"10.1080\/0886022X.2024.2327495","article-title":"Quercetin improves diabetic kidney disease by inhibiting ferroptosis and regulating the Nrf2 in streptozotocin-induced diabetic rats","volume":"46","author":"Zhang","year":"2024","journal-title":"Ren. Fail."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rahmani, A.H., Alsahli, M.A., Khan, A.A., and Almatroodi, S.A. (2023). Quercetin, a Plant Flavonol Attenuates Diabetic Complications, Renal Tissue Damage, Renal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats. Metabolites, 13.","DOI":"10.3390\/metabo13010130"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3892\/ijmm.2024.5350","article-title":"Senolytic combination of dasatinib and quercetin protects against diabetic kidney disease by activating autophagy to alleviate podocyte dedifferentiation via the Notch pathway","volume":"53","author":"Zhu","year":"2024","journal-title":"Int. J. Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1142\/S0192415X24500344","article-title":"Quercetin ameliorates myocardial injury in diabetic rats by regulating autophagy and apoptosis through AMPK\/mTOR signaling pathway","volume":"52","author":"Chen","year":"2024","journal-title":"Am. J. Chin. Med."},{"key":"ref_26","first-page":"9723632","article-title":"Quercetin inhibits pyroptosis in diabetic cardiomyopathy through the Nrf2 pathway","volume":"2022","author":"Zhang","year":"2022","journal-title":"J. Diabetes Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"142","DOI":"10.2478\/enr-2021-0015","article-title":"Quercetin improves myocardial redox status in rats with type 2 diabetes","volume":"55","author":"Gorbenko","year":"2021","journal-title":"Endocr. Regul."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chellian, J., Mak, K.K., Chellappan, D.K., Krishnappa, P., and Pichika, M.R. (2022). Quercetin and metformin synergistically reverse endothelial dysfunction in the isolated aorta of streptozotocin-nicotinamide-induced diabetic rats. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-25739-5"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Newairy, A.A., Hamaad, F.A., Wahby, M.M., Ghoneum, M., and Abdou, H.M. (2024). Neurotherapeutic effects of quercetin-loaded nanoparticles and Biochanin-A extracted from Trifolium alexandrinum on PI3K\/Akt\/GSK-3beta signaling in the cerebral cortex of male diabetic rats. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0301355"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xie, J., Song, W., Liang, X., Zhang, Q., Shi, Y., Liu, W., and Shi, X. (2020). Protective effect of quercetin on streptozotocin-induced diabetic peripheral neuropathy rats through modulating gut microbiota and reactive oxygen species level. Biomed. Pharmacother., 127.","DOI":"10.1016\/j.biopha.2020.110147"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100201","DOI":"10.1016\/j.crphar.2024.100201","article-title":"Quercetin prevents rats from type 1 diabetic liver damage by inhibiting TGF-\/apelin gene expression","volume":"7","author":"Firouzeh","year":"2024","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1002\/ptr.6486","article-title":"Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db\/db mice","volume":"33","author":"Yang","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5698119","DOI":"10.1155\/2024\/5698119","article-title":"Quercetin attenuates oxidative stress and apoptosis in brain tissue of APP\/PS1 double transgenic AD mice by regulating keap1\/Nrf2\/HO-1 pathway to improve cognitive impairment","volume":"28","author":"Cheng","year":"2024","journal-title":"Behav. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"156560","DOI":"10.1016\/j.phymed.2025.156560","article-title":"Reshaping the gut microbiota: Tangliping decoction and its core blood-absorbed component quercetin improve diabetic cognitive impairment","volume":"140","author":"Zhang","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3594","DOI":"10.1002\/ptr.8227","article-title":"Quercetin prevented diabetic nephropathy by inhibiting renal tubular epithelial cell apoptosis via the PI3K\/AKT pathway","volume":"38","author":"Liu","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chen, P., Rao, X., He, P., Liu, J., Chu, Y., Dong, Y., and Ding, M. (2025). The role of quercetin in the treatment of kidney diseases: A comprehensive review. Biomed. Pharmacother., 190.","DOI":"10.1016\/j.biopha.2025.118358"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"42390","DOI":"10.1007\/s11356-023-25254-8","article-title":"Protective effect of quercetin on pulmonary dysfunction in streptozotocin-induced diabetic rats via inhibition of NLRP3 signaling pathway","volume":"30","author":"Hegazy","year":"2023","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s10735-025-10508-1","article-title":"The effect of chitosan\/alginate hydrogel loaded quercetin on wound healing in diabetic rat model","volume":"56","author":"Larijani","year":"2025","journal-title":"J. Mol. Histol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"117337","DOI":"10.1016\/j.taap.2025.117337","article-title":"Quercetin-loaded PEGylated liposomes alleviate testicular dysfunction in alloxan-induced diabetic rats: The role of Kisspeptin\/Neurokinin B\/Dynorphin pathway","volume":"499","author":"Mansour","year":"2025","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Cappellani, F., Foti, R., Malaguarnera, G., D\u2019Esposito, F., Musumeci, C., Rapisarda, L., Tognetto, D., Gagliano, C., and Zeppieri, M. (2025). Nutrients and natural substances for hypoglycemic effects and management in diabetic retinopathy. Nutrients, 30.","DOI":"10.3390\/nu17071207"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Dawi, J., Misakyan, Y., Affa, S., Kades, S., Narasimhan, A., Hajjar, F., Besser, M., Tumanyan, K., and Venketaraman, V. (2024). Oxidative stress, glutathione insufficiency, and inflammatory pathways in type 2 diabetes mellitus: Implications for therapeutic interventions. Biomedicines, 13.","DOI":"10.3390\/biomedicines13010018"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.2337\/dbi24-0001","article-title":"Brain defense of glycemia in health and diabetes","volume":"73","author":"Mirzadeh","year":"2024","journal-title":"Diabetes"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gonzalez-Rellan, M.J., Fondevila, M.F., Dieguez, C., and Nogueiras, R. (2022). O-GlcNAcylation: A sweet hub in the regulation of glucose metabolism in health and disease. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.873513"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1016\/j.clnu.2020.12.022","article-title":"Metabolism of sugars: A window to the regulation of glucose and lipid homeostasis by splanchnic organs","volume":"40","author":"Tappy","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zhao, M., Xie, Y., Gao, W., Li, C., Ye, Q., and Li, Y. (2023). Diabetes mellitus promotes susceptibility to periodontitis: Novel insight into the molecular mechanisms. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1192625"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e70014","DOI":"10.1111\/1753-0407.70014","article-title":"Overview of oxidative stress and inflammation in diabetes","volume":"16","author":"Segev","year":"2024","journal-title":"J. Diabetes"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Wu, W., Zhang, Q., Xing, T., Bai, Y., Li, S., Zhang, D., Che, H., and Guo, X. (2025). Mechanism and therapeutic potential of hippo signaling pathway in type 2 diabetes and its complications. Biomed. Pharmacother., 183.","DOI":"10.1016\/j.biopha.2025.117817"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1093\/jn\/135.10.2299","article-title":"Quercetin decreases oxidative stress, NF-kappaB activation, and iNOS overexpression in liver of streptozotocin-induced diabetic rats","volume":"135","author":"Dias","year":"2005","journal-title":"J. Nutr."},{"key":"ref_49","first-page":"64","article-title":"Protective effect of quercetin on the morphology of pancreatic beta-cells of streptozotocin-treated diabetic rats","volume":"4","author":"Adewole","year":"2006","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3417306","DOI":"10.1155\/2017\/3417306","article-title":"Quercetin improves glucose and lipid metabolism of diabetic rats: Involvement of Akt signaling and SIRT1","volume":"2017","author":"Peng","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"633","DOI":"10.4103\/pm.pm_108_17","article-title":"Hypoglycemic, hypolipidemic, and wound healing potential of quercetin in streptozotocin-induced diabetic rats","volume":"13","author":"Ahmad","year":"2017","journal-title":"Pharmacogn. Mag."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jpha.2017.10.005","article-title":"Anti-diabetic activity of quercetin extracted from Phyllanthus emblica L. fruit: In silico and in vivo approaches","volume":"8","author":"Srinivasan","year":"2018","journal-title":"J. Pharm. Anal."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.taap.2018.12.011","article-title":"Modulating impacts of quercetin\/sitagliptin combination on streptozotocin-induced diabetes mellitus in rats","volume":"365","author":"Eitah","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/cbf.3678","article-title":"Antidiabetic effects of quercetin and liraglutide combination through modulation of TXNIP\/IRS-1\/PI3K pathway","volume":"40","author":"Eraky","year":"2022","journal-title":"Cell Biochem. Funct."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s00125-007-0886-7","article-title":"The mechanisms of alloxan- and streptozotocin-induced diabetes","volume":"51","author":"Lenzen","year":"2008","journal-title":"Diabetologia"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1258\/ebm.2012.011372","article-title":"Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model","volume":"237","author":"Szkudelski","year":"2012","journal-title":"Exp. Biol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/j.bbagen.2017.05.013","article-title":"Chemistry and biology of reactive species with special reference to the antioxidative defence status in pancreatic beta-cells","volume":"1861","author":"Lenzen","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e13703","DOI":"10.1111\/obr.13703","article-title":"Mechanisms of lipotoxicity-induced dysfunction and death of human pancreatic beta cells under obesity and type 2 diabetes conditions","volume":"25","author":"Lenzen","year":"2024","journal-title":"Obes. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e135","DOI":"10.1038\/nutd.2014.30","article-title":"You are what you eat, or are you? The challenges of translating high-fat-fed rodents to human obesity and diabetes","volume":"4","author":"Lai","year":"2014","journal-title":"Nutr. Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2902351","DOI":"10.1155\/2016\/2902351","article-title":"An overview of murine high fat diet as a model for type 2 diabetes mellitus","volume":"2016","author":"Heydemann","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Stachura, A., Khanna, I., Krysiak, P., Paskal, W., and W\u0142odarski, P. (2022). Wound healing impairment in type 2 diabetes model of leptin-deficient mice: A mechanistic systematic review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158621"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Abdou, H.M., Hamaad, F.A., Ali, E.Y., and Ghoneum, M.H. (2022). Antidiabetic efficacy of Trifolium alexandrinum extracts hesperetin and quercetin in ameliorating carbohydrate metabolism and activating IR and AMPK signaling in the pancreatic tissues of diabetic rats. Biomed. Pharmacother., 149.","DOI":"10.1016\/j.biopha.2022.112838"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4162\/nrp.2011.5.2.107","article-title":"Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus","volume":"5","author":"Kim","year":"2011","journal-title":"Nutr. Res. Pract."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"201","DOI":"10.4162\/nrp.2012.6.3.201","article-title":"Quercetin ameliorates hyperglycemia and dyslipidemia and improves antioxidant status in type 2 diabetic db\/db mice","volume":"6","author":"Jeong","year":"2012","journal-title":"Nutr. Res. Pract."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7015","DOI":"10.18632\/aging.103059","article-title":"Quercetin ameliorates diabetic encephalopathy through SIRT1\/ER stress pathway in db\/db mice","volume":"12","author":"Hu","year":"2020","journal-title":"Aging"},{"key":"ref_66","first-page":"629","article-title":"Quercetin protects islet beta-cells from oxidation-induced apoptosis via Sirt3 in T2DM","volume":"24","author":"Wang","year":"2021","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Yuan, M., Sun, T., Zhang, Y., Guo, C., Wang, F., Yao, Z., and Yu, L. (2024). Quercetin alleviates insulin resistance and repairs intestinal barrier in db\/db mice by modulating gut microbiota. Nutrients, 16.","DOI":"10.3390\/nu16121870"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Li, D., Jiang, C., Mei, G., Zhao, Y., Chen, L., Liu, J., Tang, Y., Gao, C., and Yao, P. (2020). Quercetin alleviates ferroptosis of pancreatic beta cells in type 2 diabetes. Nutrients, 12.","DOI":"10.3390\/nu12102954"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Tan, Y., Tam, C.C., Rolston, M., Alves, P., Chen, L., Meng, S., Hong, H., Chang, S.K.C., and Yokoyama, W. (2021). Quercetin ameliorates insulin resistance and restores gut microbiome in mice on high-fat diets. Antioxidants, 10.","DOI":"10.3390\/antiox10081251"},{"key":"ref_70","first-page":"149","article-title":"Anti-diabetic effect of quercetin in type 2 diabetes mellitus by regulating the microRNA-92b-3p\/EGR1 axis","volume":"74","author":"Ke","year":"2023","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Luthra, S., Viola, L., Navaratnarajah, M., Thirukumaran, D., and Velissaris, T. (2024). Glycated Haemoglobin (HbA(1C)) in cardiac surgery: A narrative review. J. Clin. Med., 14.","DOI":"10.20944\/preprints202409.1633.v1"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1177\/1479164119827611","article-title":"Insulin resistance and insulin hypersecretion in the metabolic syndrome and type 2 diabetes: Time for a conceptual framework shift","volume":"16","author":"Nolan","year":"2019","journal-title":"Diab. Vasc. Dis. Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Janssen, J.A.M.J.L. (2024). Overnutrition, hyperinsulinemia and ectopic fat: It is time for a paradigm shift in the management of type 2 diabetes. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105488"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1730492","DOI":"10.1155\/2020\/1730492","article-title":"Antidiabetic Potency, Antioxidant Effects, and Mode of Actions of Citrus reticulata Fruit Peel Hydroethanolic Extract, Hesperidin, and Quercetin in Nicotinamide\/Streptozotocin-Induced Wistar Diabetic Rats","volume":"2020","author":"Ali","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1089\/ars.2016.6755","article-title":"The role of oxidative stress and hypoxia in pancreatic beta-cell dysfunction in diabetes mellitus","volume":"26","author":"Gerber","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"122546","DOI":"10.1016\/j.lfs.2024.122546","article-title":"Lipid nanoparticles of quercetin (QU-Lip) alleviated pancreatic microenvironment in diabetic male rats: The interplay between oxidative stress\u2014Unfolded protein response (UPR)\u2014Autophagy, and their regulatory miRNA","volume":"344","author":"Khater","year":"2024","journal-title":"Life Sci."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Hadi, A., Pourmasoumi, M., Najafgholizadeh, A., Clark, C.C.T., and Esmaillzadeh, A. (2021). The effect of apple cider vinegar on lipid profiles and glycemic parameters: A systematic review and meta-analysis of randomized clinical trials. BMC Complement. Med. Ther., 21.","DOI":"10.1186\/s12906-021-03351-w"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e00248","DOI":"10.1016\/j.plabm.2021.e00248","article-title":"Diabetic dyslipidaemia","volume":"26","author":"Thambiah","year":"2021","journal-title":"Pract. Lab. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1186\/s12944-024-02352-1","article-title":"ANGPTL3 as a target for treating lipid disorders in type 2 diabetes patients","volume":"23","author":"Chen","year":"2024","journal-title":"Lipids Health Dis."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Handy, R.M., and Holloway, G.P. (2023). Insights into the development of insulin resistance: Unraveling the interaction of physical inactivity, lipid metabolism and mitochondrial biology. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1151389"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/978-3-031-63657-8_14","article-title":"Insulin resistance, obesity, and lipotoxicity","volume":"1460","author":"Demir","year":"2024","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"117545","DOI":"10.1016\/j.atherosclerosis.2024.117545","article-title":"Modification of lipoprotein metabolism and function driving atherogenesis in diabetes","volume":"394","author":"Luciani","year":"2024","journal-title":"Atherosclerosis"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Reddy, V.P. (2023). Oxidative stress in health and disease. Biomedicines, 11.","DOI":"10.3390\/biomedicines11112925"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Dilworth, L., Stennett, D., Facey, A., Omoruyi, F., Mohansingh, S., and Omoruyi, F.O. (2024). Diabetes and the associated complications: The role of antioxidants in diabetes therapy and care. Biomed. Pharmacother., 181.","DOI":"10.1016\/j.biopha.2024.117641"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"114185","DOI":"10.1016\/j.intimp.2025.114185","article-title":"Advances in the pathogenesis and treatment strategies for type 1 diabetes mellitus","volume":"148","author":"Du","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Veluthakal, R., Esparza, D., Hoolachan, J.M., Balakrishnan, R., Ahn, M., Oh, E., Jayasena, C.S., and Thurmond, D.C. (2024). Mitochondrial dysfunction, oxidative stress, and inter-organ miscommunications in T2D progression. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031504"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.fct.2014.06.010","article-title":"Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver, kidney and pancreas tissues of STZ-induced diabetic rats: A mechanistic study","volume":"71","author":"Arya","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Mohammadi-Motlagh, H.R., Sadeghalvad, M., Yavari, N., Primavera, R., Soltani, S., Chetty, S., Ganguly, A., Regmi, S., Fl\u00f8yel, T., and Kaur, S. (2023). Beta cell and autophagy: What do we know?. Biomolecules, 13.","DOI":"10.3390\/biom13040649"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1080\/07435800.2024.2413064","article-title":"Pancreatic beta-Cells, Diabetes and Autophagy","volume":"50","author":"Ou","year":"2025","journal-title":"Endocr. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s40200-022-00987-4","article-title":"Quercetin prevents insulin dysfunction in hypertensive animals","volume":"21","author":"Serra","year":"2022","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1038\/s41467-021-25367-z","article-title":"Tet2 controls the responses of beta cells to inflammation in autoimmune diabetes","volume":"12","author":"Rui","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.cmet.2013.05.018","article-title":"Metabolic signaling in fuel-induced insulin secretion","volume":"18","author":"Prentki","year":"2013","journal-title":"Cell Metab."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1007\/s00125-020-05205-5","article-title":"Metabolic and functional specialisations of the pancreatic beta cell: Gene disallowance, mitochondrial metabolism and intercellular connectivity","volume":"63","author":"Rutter","year":"2020","journal-title":"Diabetologia"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Kosmalski, M., Zi\u00f3\u0142kowska, S., Czarny, P., Szemraj, J., and Pietras, T. (2022). The coexistence of nonalcoholic fatty liver disease and type 2 diabetes mellitus. J. Clin. Med., 11.","DOI":"10.3390\/jcm11051375"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"200","DOI":"10.2478\/enr-2023-0024","article-title":"Role of liver parameters in diabetes mellitus: A narrative review","volume":"57","author":"Rafaqat","year":"2023","journal-title":"Endocr. Regul."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/S2221-1691(12)60090-2","article-title":"Anti-oxidative role of quercetin derived from Allium cepa on aldehyde oxidase (OX-LDL) and hepatocytes apoptosis in streptozotocin-induced diabetic rat","volume":"2","author":"Bakhshaeshi","year":"2012","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Mata-Torres, G., Andrade-Cetto, A., and Espinoza-Hern\u00e1ndez, F. (2021). Approaches to decrease hyperglycemia by targeting impaired hepatic glucose homeostasis using medicinal plants. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.809994"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.pop.2024.03.003","article-title":"Glucose disorders","volume":"51","author":"Perez","year":"2024","journal-title":"Prim. Care"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1507\/endocrj.EJ24-0192","article-title":"Physiological and pathophysiological actions of insulin in the liver","volume":"72","author":"Kubota","year":"2025","journal-title":"Endocr. J."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Chen, C.L., Tseng, P.C., Satria, R.D., Nguyen, T.T., Tsai, C.C., and Lin, C.F. (2022). Role of glycogen synthase kinase-3 in interferon-gamma-mediated immune hepatitis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094669"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"107037","DOI":"10.1016\/j.phrs.2023.107037","article-title":"SIRT1\/SREBPs-mediated regulation of lipid metabolism","volume":"199","author":"Shen","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e17094","DOI":"10.7717\/peerj.17094","article-title":"The role of sirtuin1 in liver injury: Molecular mechanisms and novel therapeutic target","volume":"12","author":"Wang","year":"2024","journal-title":"PeerJ"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1507\/endocrj.EJ23-0150","article-title":"Unraveling the mysteries of hepatic insulin signaling: Deconvoluting the nuclear targets of insulin","volume":"70","author":"Kitamoto","year":"2023","journal-title":"Endocr. J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1248\/bpb.30.1610","article-title":"Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions","volume":"30","author":"Asano","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2131\/jts.45.515","article-title":"Specificity of transaminase activities in the prediction of drug-induced hepatotoxicity","volume":"45","author":"Kobayashi","year":"2020","journal-title":"J. Toxicol. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Ahmad, K., Shaikh, S., Lim, J.H., Ahmad, S.S., Chun, H.J., Lee, E.J., and Choi, I. (2023). Therapeutic application of natural compounds for skeletal muscle-associated metabolic disorders: A review on diabetes perspective. Biomed. Pharmacother., 168.","DOI":"10.1016\/j.biopha.2023.115642"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"112466","DOI":"10.1016\/j.mce.2025.112466","article-title":"Skeletal muscle disorders as risk factors for type 2 diabetes","volume":"599","author":"Tammineni","year":"2025","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_108","first-page":"239","article-title":"Effects of quercetin and coenzyme Q10 on biochemical, molecular, and morphological parameters of skeletal muscle in trained diabetic rats","volume":"15","author":"Youssef","year":"2022","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_109","first-page":"457","article-title":"Eur fructooligosaccharide augments benefits of quercetin-3-O-beta-glucoside on insulin sensitivity and plasma total cholesterol with promotion of flavonoid absorption in sucrose-fed rats","volume":"53","author":"Phuwamongkolwiwat","year":"2014","journal-title":"J. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.lfs.2014.06.005","article-title":"Protective effect of quercetin on hyperglycemia, oxidative stress and DNA damage in alloxan induced type 2 diabetic mice","volume":"109","author":"Alam","year":"2014","journal-title":"Life Sci."},{"key":"ref_111","first-page":"8095926","article-title":"Adipokines: Potential therapeutic targets for vascular dysfunction in type II diabetes mellitus and obesity","volume":"2017","author":"Mamdouh","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"275","DOI":"10.7570\/jomes24013","article-title":"Understanding adipose tissue dysfunction","volume":"33","year":"2024","journal-title":"J. Obes. Metab. Syndr."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Bahadoran, Z., Mirmiran, P., and Ghasemi, A. (2024). Adipose organ dysfunction and type 2 diabetes: Role of nitric oxide. Biochem. Pharmacol., 221.","DOI":"10.1016\/j.bcp.2024.116043"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Parra-Peralbo, E., Talamillo, A., and Barrio, R. (2021). Origin and development of the adipose tissue, a key organ in physiology and disease. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.786129"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"595","DOI":"10.4093\/dmj.2023.0011","article-title":"Adipose tissue and metabolic health","volume":"47","author":"An","year":"2023","journal-title":"Diabetes Metab. J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s13105-024-01060-9","article-title":"Modification of adipogenesis and oxidative stress by quercetin: Positive or negative impact on adipose tissue metabolism of obese diabetic Zucker rats?","volume":"81","author":"Bozorgnia","year":"2025","journal-title":"J. Physiol. Biochem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"loae003","DOI":"10.1093\/lifemeta\/loae003","article-title":"The secretory function of adipose tissues in metabolic regulation","volume":"3","author":"Liu","year":"2024","journal-title":"Life Metab."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Hemat Jouy, S., Mohan, S., Scichilone, G., Mostafa, A., and Mahmoud, A.M. (2024). Adipokines in the crosstalk between adipose tissues and other organs: Implications in cardiometabolic diseases. Biomedicines, 12.","DOI":"10.3390\/biomedicines12092129"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ando.2024.04.002","article-title":"Biological markers of adipose tissue: Adipokines","volume":"85","author":"Bastard","year":"2024","journal-title":"Ann. Endocrinol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"377","DOI":"10.5114\/bta.2024.145258","article-title":"Quercetin nanoparticles as a therapeutic approach: Pharmacological actions and potential applications in therapy","volume":"105","author":"Baiomy","year":"2024","journal-title":"BioTechnologia"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"5594462","DOI":"10.1155\/2024\/5594462","article-title":"Therapeutic efficacy of quercetin and its nanoformulation both the mono- or combination therapies in the management of cancer: An update with molecular mechanisms","volume":"2024","author":"Eity","year":"2024","journal-title":"J. Trop. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"9727539","DOI":"10.1155\/2023\/9727539","article-title":"A Pharmacokinetic study of different quercetin formulations in healthy participants: A diet-controlled, crossover, single- and multiple-dose pilot study","volume":"2023","author":"Solnier","year":"2023","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1093\/jn\/131.10.2648","article-title":"Carbon dioxide is the major metabolite of quercetin in humans","volume":"131","author":"Walle","year":"2001","journal-title":"J. Nutr."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"57","DOI":"10.2478\/enr-2025-0008","article-title":"Role of medicinal plants in ameliorating the lipid and glucose levels in diabetes: A systematic literature review","volume":"59","author":"Yong","year":"2025","journal-title":"Endocr. Regul."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"155437","DOI":"10.1016\/j.phymed.2024.155437","article-title":"Rutin ameliorated lipid metabolism dysfunction of diabetic NAFLD via AMPK\/SREBP1 pathway","volume":"126","author":"Liu","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/01652176.2024.2372090","article-title":"Efficacy of quercetin-like compounds from the mistletoe plant of Dendrophthoe pentandra L. Miq, as oral random blood sugar lowering treatment in diabetic rats","volume":"44","author":"Lazuardi","year":"2024","journal-title":"Vet. Q."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"5907","DOI":"10.1021\/acs.jafc.1c01388","article-title":"Combination of alpha-glycosyl-isoquercitrin and soybean fiber promotes quercetin bioavailability and glucagon-like peptide-1 secretion and improves glucose homeostasis in rats fed a high-fat high-sucrose diet","volume":"69","author":"Trakooncharoenvit","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Rey, D., Fernandes, T.A., Sulis, P.M., Gon\u00e7alves, R., Sep\u00falveda, R.M., Silva Frederico, M.J., Aragon, M., Ospina, L.F., Costa, G.M., and Silva, F.R.M.B. (2020). Cellular target of isoquercetin from Passiflora ligularis Juss for glucose uptake in rat soleus muscle. Chem. Biol. Interact., 330.","DOI":"10.1016\/j.cbi.2020.109198"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ejphar.2011.06.022","article-title":"Anti-diabetic effects of pentamethylquercetin in neonatally streptozotocin-induced diabetic rats","volume":"668","author":"Wang","year":"2011","journal-title":"Eur. J. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7391\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:19:32Z","timestamp":1760033972000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":129,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26157391"],"URL":"https:\/\/doi.org\/10.3390\/ijms26157391","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,31]]}}}