{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T14:34:23Z","timestamp":1793025263773,"version":"4.5.0"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Research Centre Egypt"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Diabetes mellitus (DM) represents a multifactorial condition linked to hyperglycemia, which, can lead to damage across multiple organs, including the lungs. Nod-like receptor protein-3 (NLRP3)- mediated pyroptosis could contribute to the onset of DM consequences. Several approaches have been established aimed to minimizing the complications associated with DM. Among these, linagliptin and vildagliptin, di-peptidyl peptidase-4 (DPP-4) inhibitors, are known to exert not only antihyperglycemic effects but also additional beneficial biological activities. The current study investigated the impact of linagliptin and vildagliptin on pulmonary function, oxidative stress, and NLRP3-induced pyroptosis in rats. Thirty-two male Sprague Dawley rats were given a 7-day acclimatization period. A single intraperitoneal injection of freshly produced STZ (60\u00a0mg\/kg) was utilized to develop DM type-1 in rats. Following STZ treatment, all rats were given a 5% glucose solution overnight. Blood glucose levels were monitored in overnight fasted rats 72\u00a0h later, with a threshold of 250\u00a0mg\/dL or higher confirming the onset of DM. The diabetic rats were randomly allocated to treated daily with either vildagliptin (5\u00a0mg\/kg\/p.o.) or linagliptin (5\u00a0mg\/kg\/p.o.) for 30 days. Additionally, the typical control group received merely the vehicle. The findings revealed that vildagliptin improves pulmonary dysfunctions associated with DM by restoring glucose homeostasis, insulin, redox marker levels, and inflammatory indices. Additionally, the NLRP3-pyroptosis-mediated IL-1\u03b2 was suppressed. Vildagliptin has been shown to mitigate the detrimental effects of diabetes mellitus (DM) on the lungs, as evidenced by a reduction in pathological lung alterations and a decrease in Caspase 3 expression, which is indicative of immunohistochemical changes. In conclusion, pyroptosis triggered by the NLRP3 inflammasome possibly exacerbate diabetic pulmonary injury in rats. Vildagliptin is superior to linagliptin in ameliorating diabetes-induced lung injury primarily via targeting the NLRP3 inflammasome pathway.<\/jats:p>","DOI":"10.1038\/s41598-025-07204-1","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T04:37:25Z","timestamp":1750826245000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Unravelling the mechanism by which vildagliptin and linagliptin inhibit pyroptosis in lung injury through the NLRP3 inflammatory pathway in type 1 diabetic rats"],"prefix":"10.1038","volume":"15","author":[{"given":"Ahmed A.","family":"Sedik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesma M. E. Abo","family":"El-Nasr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wagdy K. B.","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliaa E. M. K.","family":"El-Mosallamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"7204_CR1","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/nrendo.2017.151","volume":"14","author":"Y Zheng","year":"2018","unstructured":"Zheng, Y., Ley, S. H. & Hu, F. B. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat. Rev. Endocrinol. 14, 88\u201398. https:\/\/doi.org\/10.1038\/nrendo.2017.151 (2018).","journal-title":"Nat. Rev. Endocrinol."},{"key":"7204_CR2","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1038\/nm.4350","volume":"23","author":"MP Czech","year":"2017","unstructured":"Czech, M. P. Insulin action and resistance in obesity and type 2 diabetes. Nat. Med. 23, 804\u2013814. https:\/\/doi.org\/10.1038\/nm.4350 (2017).","journal-title":"Nat. Med."},{"key":"7204_CR3","doi-asserted-by":"publisher","first-page":"11920","DOI":"10.1038\/s41598-018-30449-y","volume":"8","author":"G Talakatta","year":"2018","unstructured":"Talakatta, G. et al. Diabetes induces fibrotic changes in the lung through the activation of TGF-beta signaling pathways. Sci. Rep. 8, 11920. https:\/\/doi.org\/10.1038\/s41598-018-30449-y (2018).","journal-title":"Sci. Rep."},{"key":"7204_CR4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.14336\/AD.2016.0627","volume":"8","author":"H Zheng","year":"2017","unstructured":"Zheng, H., Wu, J., Jin, Z. & Yan, L. J. Potential biochemical mechanisms of lung injury in diabetes. Aging Dis. 8, 7\u201316. https:\/\/doi.org\/10.14336\/AD.2016.0627 (2017).","journal-title":"Aging Dis."},{"key":"7204_CR5","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s12931-020-01334-y","volume":"21","author":"R Sudy","year":"2020","unstructured":"Sudy, R. et al. Lung volume dependence of respiratory function in rodent models of diabetes mellitus. Respir Res. 21, 82. https:\/\/doi.org\/10.1186\/s12931-020-01334-y (2020).","journal-title":"Respir Res."},{"key":"7204_CR6","doi-asserted-by":"publisher","first-page":"3207","DOI":"10.1002\/jcp.29268","volume":"235","author":"F Lu","year":"2020","unstructured":"Lu, F. et al. Emerging insights into molecular mechanisms underlying pyroptosis and functions of inflammasomes in diseases. J. Cell. Physiol. 235, 3207\u20133221. https:\/\/doi.org\/10.1002\/jcp.29268 (2020).","journal-title":"J. Cell. Physiol."},{"key":"7204_CR7","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nature22967","volume":"546","author":"S Zhu","year":"2017","unstructured":"Zhu, S. et al. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells. Nature 546, 667\u2013670. https:\/\/doi.org\/10.1038\/nature22967 (2017).","journal-title":"Nature"},{"key":"7204_CR8","doi-asserted-by":"publisher","first-page":"117138","DOI":"10.1016\/j.lfs.2019.117138","volume":"240","author":"ZW Yu","year":"2020","unstructured":"Yu, Z. W. et al. A new research hot spot: The role of NLRP3 inflammasome activation, a key step in pyroptosis, in diabetes and diabetic complications. Life Sci. 240, 117138. https:\/\/doi.org\/10.1016\/j.lfs.2019.117138 (2020).","journal-title":"Life Sci."},{"key":"7204_CR9","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1038\/cr.2015.139","volume":"25","author":"WT He","year":"2015","unstructured":"He, W. T. et al. Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion. Cell. Res. 25, 1285\u20131298. https:\/\/doi.org\/10.1038\/cr.2015.139 (2015).","journal-title":"Cell. Res."},{"key":"7204_CR10","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/S0140-6736(01)05415-0","volume":"358","author":"MA Atkinson","year":"2001","unstructured":"Atkinson, M. A. & Eisenbarth, G. S. Type 1 diabetes: New perspectives on disease pathogenesis and treatment. Lancet 358, 221\u2013229. https:\/\/doi.org\/10.1016\/S0140-6736(01)05415-0 (2001).","journal-title":"Lancet"},{"key":"7204_CR11","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.cmet.2006.01.004","volume":"3","author":"DJ Drucker","year":"2006","unstructured":"Drucker, D. J. The biology of incretin hormones. Cell. Metab. 3, 153\u2013165. https:\/\/doi.org\/10.1016\/j.cmet.2006.01.004 (2006).","journal-title":"Cell. Metab."},{"key":"7204_CR12","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1080\/13543776.2024.2446226","volume":"35","author":"G Abbas","year":"2024","unstructured":"Abbas, G. et al. Dipeptidyl peptidase IV inhibitors as a potential target for diabetes: Patent review 2019 \u2013 present. Expert Opin. Ther. Pat. 35, 239\u2013250. https:\/\/doi.org\/10.1080\/13543776.2024.2446226 (2024).","journal-title":"Expert Opin. Ther. Pat."},{"key":"7204_CR13","doi-asserted-by":"publisher","first-page":"731453","DOI":"10.3389\/fphar.2021.731453","volume":"12","author":"T Zhang","year":"2021","unstructured":"Zhang, T. et al. The roles of dipeptidyl peptidase 4 (DPP4) and DPP4 inhibitors in different lung diseases: New evidence. Front. Pharmacol. 12, 731453. https:\/\/doi.org\/10.3389\/fphar.2021.731453 (2021).","journal-title":"Front. Pharmacol."},{"key":"7204_CR14","doi-asserted-by":"publisher","first-page":"571","DOI":"10.2174\/1871530321666210809153558","volume":"22","author":"A Alshanwani","year":"2022","unstructured":"Alshanwani, A., Kashour, T. & Badr, A. Anti-diabetic drugs GLP-1 agonists and DPP-4 inhibitors May represent potential therapeutic approaches for COVID-19. Endocr. Metab. Immune Disord. Drug Targets 22, 571\u2013578. https:\/\/doi.org\/10.2174\/1871530321666210809153558 (2022).","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"7204_CR15","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.2337\/diabetes.51.5.1461","volume":"51","author":"B Sudre","year":"2002","unstructured":"Sudre, B. et al. Chronic Inhibition of Circulating dipeptidyl peptidase IV by FE 999011 delays the occurrence of diabetes in male Zucker diabetic fatty rats. Diabetes 51, 1461\u20131469. https:\/\/doi.org\/10.2337\/diabetes.51.5.1461 (2002).","journal-title":"Diabetes"},{"key":"7204_CR16","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s12931-017-0660-4","volume":"18","author":"T Suzuki","year":"2017","unstructured":"Suzuki, T. et al. Vildagliptin ameliorates pulmonary fibrosis in lipopolysaccharide-induced lung injury by inhibiting endothelial-to-mesenchymal transition. Respir Res. 18, 177. https:\/\/doi.org\/10.1186\/s12931-017-0660-4 (2017).","journal-title":"Respir Res."},{"key":"7204_CR17","doi-asserted-by":"publisher","first-page":"113704","DOI":"10.1016\/j.biopha.2022.113704","volume":"155","author":"N Zhang","year":"2022","unstructured":"Zhang, N. et al. The dipeptidyl peptidase-4 inhibitor linagliptin ameliorates LPS-induced acute lung injury by maintenance of pulmonary microvascular barrier via activating the Epac1\/AKT pathway. Biomed. Pharmacother. 155, 113704. https:\/\/doi.org\/10.1016\/j.biopha.2022.113704 (2022).","journal-title":"Biomed. Pharmacother"},{"key":"7204_CR18","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.3390\/ijms11052056","volume":"11","author":"OO Erejuwa","year":"2010","unstructured":"Erejuwa, O. O. et al. Antioxidant protective effect of glibenclamide and metformin in combination with honey in pancreas of streptozotocin-induced diabetic rats. Int. J. Mol. Sci. 11, 2056\u20132066. https:\/\/doi.org\/10.3390\/ijms11052056 (2010).","journal-title":"Int. J. Mol. Sci."},{"key":"7204_CR19","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.jep.2010.01.025","volume":"128","author":"R Pandit","year":"2010","unstructured":"Pandit, R., Phadke, A. & Jagtap, A. Antidiabetic effect of Ficus religiosa extract in streptozotocin-induced diabetic rats. J. Ethnopharmacol. 128, 462\u2013466. https:\/\/doi.org\/10.1016\/j.jep.2010.01.025 (2010).","journal-title":"J. Ethnopharmacol."},{"key":"7204_CR20","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.arcmed.2013.03.004","volume":"44","author":"L Avila Dde","year":"2013","unstructured":"Avila Dde, L. et al. Vildagliptin ameliorates oxidative stress and pancreatic beta cell destruction in type 1 diabetic rats. Arch. Med. Res. 44, 194\u2013202. https:\/\/doi.org\/10.1016\/j.arcmed.2013.03.004 (2013).","journal-title":"Arch. Med. Res."},{"key":"7204_CR21","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1248\/bpb.b23-00737","volume":"47","author":"ME Nady","year":"2024","unstructured":"Nady, M. E., El-Raouf, A., El-Sayed, E. M. & O. M. & Linagliptin mitigates TGF-beta1 mediated epithelial-mesenchymal transition in tacrolimus-induced renal interstitial fibrosis via smad\/ERK\/P38 and HIF-1alpha\/LOXL2 signaling pathways. Biol. Pharm. Bull. 47, 1008\u20131020. https:\/\/doi.org\/10.1248\/bpb.b23-00737 (2024).","journal-title":"Biol. Pharm. Bull."},{"key":"7204_CR22","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1177\/000456326900600108","volume":"6","author":"P Trinder","year":"1969","unstructured":"Trinder, P. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann. Clin. Biochem. 6, 24\u201327 (1969).","journal-title":"Ann. Clin. Biochem."},{"key":"7204_CR23","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1172\/JCI102583","volume":"31","author":"J Groen","year":"1952","unstructured":"Groen, J., Kamminga, C. E., Willebrands, A. F. & Blickman, J. R. Evidence for the presence of insulin in blood serum; a method for an approximate determination of the insulin content of blood. J. Clin. Invest. 31, 97\u2013106. https:\/\/doi.org\/10.1172\/JCI102583 (1952).","journal-title":"J. Clin. Invest."},{"key":"7204_CR24","doi-asserted-by":"publisher","first-page":"3363","DOI":"10.1007\/s00210-023-02833-7","volume":"397","author":"A Salama","year":"2024","unstructured":"Salama, A., Gouida, M. S. O., Yassen, N. N. & Sedik, A. A. Immunoregulatory role of hesperidin against ovalbumin (OVA)-induced bronchial asthma and depression in rats. Naunyn Schmiedebergs Arch. Pharmacol. 397, 3363\u20133378. https:\/\/doi.org\/10.1007\/s00210-023-02833-7 (2024).","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"7204_CR25","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","volume":"95","author":"H Ohkawa","year":"1979","unstructured":"Ohkawa, H., Ohishi, N. & Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95, 351\u2013358. https:\/\/doi.org\/10.1016\/0003-2697(79)90738-3 (1979).","journal-title":"Anal. Biochem."},{"key":"7204_CR26","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1159\/000136485","volume":"11","author":"DJ Jollow","year":"1974","unstructured":"Jollow, D. J., Mitchell, J. R., Zampaglione, N. & Gillette, J. R. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11, 151\u2013169. https:\/\/doi.org\/10.1159\/000136485 (1974).","journal-title":"Pharmacology"},{"key":"7204_CR27","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1093\/clinchem\/34.3.497","volume":"34","author":"Y Sun","year":"1988","unstructured":"Sun, Y., Oberley, L. W. & Li, Y. A simple method for clinical assay of superoxide dismutase. Clin. Chem. 34, 497\u2013500 (1988).","journal-title":"Clin. Chem."},{"key":"7204_CR28","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1038\/s41598-024-82921-7","volume":"15","author":"SS Soliman","year":"2025","unstructured":"Soliman, S. S., Suliman, A. A., Fathy, K. & Sedik, A. A. Ovario-protective effect of Moringa oleifera leaf extract against cyclophosphamide-induced oxidative ovarian damage and reproductive dysfunction in female rats. Sci. Rep. 15, 1054 (2025).","journal-title":"Sci. Rep."},{"key":"7204_CR29","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1007\/s10787-017-0424-2","volume":"26","author":"NA Salem","year":"2018","unstructured":"Salem, N. A., Wahba, M. A., Eisa, W. H., El-Shamarka, M. & Khalil, W. Silver oxide nanoparticles alleviate indomethacin-induced gastric injury: a novel antiulcer agent. Inflammopharmacology 26, 1025\u20131035. https:\/\/doi.org\/10.1007\/s10787-017-0424-2 (2018).","journal-title":"Inflammopharmacology"},{"key":"7204_CR30","doi-asserted-by":"publisher","first-page":"413","DOI":"10.2147\/DDDT.S344240","volume":"16","author":"M Shi","year":"2022","unstructured":"Shi, M. et al. Protective effects of remimazolam on cerebral ischemia\/reperfusion injury in rats by inhibiting of NLRP3 Inflammasome-Dependent pyroptosis. Drug Des. Devel Ther. 16, 413\u2013423. https:\/\/doi.org\/10.2147\/DDDT.S344240 (2022).","journal-title":"Drug Des. Devel Ther."},{"key":"7204_CR31","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1080\/1354750X.2021.1999504","volume":"26","author":"MA Hamed","year":"2021","unstructured":"Hamed, M. A. et al. Bioactive compounds and therapeutic role of Brassica oleracea L. seeds in rheumatoid arthritis rats via regulating inflammatory signalling pathways and antagonizing interleukin-1 receptor action. Biomarkers 26, 788\u2013807. https:\/\/doi.org\/10.1080\/1354750X.2021.1999504 (2021).","journal-title":"Biomarkers"},{"key":"7204_CR32","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.phymed.2018.01.026","volume":"41","author":"T Ding","year":"2018","unstructured":"Ding, T. et al. Kidney protection effects of dihydroquercetin on diabetic nephropathy through suppressing ROS and NLRP3 inflammasome. Phytomedicine 41, 45\u201353. https:\/\/doi.org\/10.1016\/j.phymed.2018.01.026 (2018).","journal-title":"Phytomedicine"},{"key":"7204_CR33","doi-asserted-by":"publisher","first-page":"83356","DOI":"10.1007\/s11356-023-28182-9","volume":"30","author":"AA Sedik","year":"2023","unstructured":"Sedik, A. A., Hassan, S. A., Shafey, H. I., Khalil, W. K. B. & Mowaad, N. A. Febuxostat attenuates aluminum chloride-induced hepatorenal injury in rats with the impact of Nrf2, crat, Car3, and MNK-mediated apoptosis. Environ. Sci. Pollut Res. Int. 30, 83356\u201383375. https:\/\/doi.org\/10.1007\/s11356-023-28182-9 (2023).","journal-title":"Environ. Sci. Pollut Res. Int."},{"key":"7204_CR34","doi-asserted-by":"publisher","first-page":"12515","DOI":"10.1096\/fj.201802805RR","volume":"33","author":"Y An","year":"2019","unstructured":"An, Y. et al. Activation of ROS\/MAPKs\/NF-kappaB\/NLRP3 and Inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis. FASEB J. 33, 12515\u201312527. https:\/\/doi.org\/10.1096\/fj.201802805RR (2019).","journal-title":"FASEB J."},{"key":"7204_CR35","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.19540\/j.cnki.cjcmm.20230113.401","volume":"48","author":"CD Song","year":"2023","unstructured":"Song, C. D. et al. Effect of multi-glycosides of Tripterygium wilfordii on renal injury in diabetic kidney disease rats through NLRP3\/caspase-1\/GSDMD pyroptosis pathway]. Zhongguo Zhong Yao Za Zhi. 48, 2639\u20132645. https:\/\/doi.org\/10.19540\/j.cnki.cjcmm.20230113.401 (2023).","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"7204_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3892\/ijmm.2023.5252","volume":"51","author":"L Yang","year":"2023","unstructured":"Yang, L. et al. Berberine blocks inflammasome activation and alleviates diabetic cardiomyopathy via the miR\u201318a\u20133p\/Gsdmd pathway. Int. J. Mol. Med. 51, 1\u201313. https:\/\/doi.org\/10.3892\/ijmm.2023.5252 (2023).","journal-title":"Int. J. Mol. Med."},{"key":"7204_CR37","unstructured":"Bancroft, J. D. & Cook, H. C. Manual of histological techniques  (1984)."},{"key":"7204_CR38","doi-asserted-by":"publisher","first-page":"84791","DOI":"10.1007\/s11356-023-28184-7","volume":"30","author":"AA Sedik","year":"2023","unstructured":"Sedik, A. A., Hassan, A. & Saleh, D. O. Neuromodulatory role of L-arginine: nitric oxide precursor against thioacetamide-induced-hepatic encephalopathy in rats via downregulation of NF-kappaB-mediated apoptosis. Environ. Sci. Pollut Res. Int. 30, 84791\u201384804. https:\/\/doi.org\/10.1007\/s11356-023-28184-7 (2023).","journal-title":"Environ. Sci. Pollut Res. Int."},{"key":"7204_CR39","first-page":"107","volume":"66","author":"A Sedik","year":"2023","unstructured":"Sedik, A., Hassan, A. & A. & Attenuation of sodium fluoride-induced hepatic injury by Lactobacillus casei through Inhibition of NF-\u03ba\u03b2 signalling pathway with decreased expression of caspase-3 in rats. Egypt. J. Chem. 66, 107\u2013123 (2023).","journal-title":"Egypt. J. Chem."},{"key":"7204_CR40","doi-asserted-by":"publisher","first-page":"686","DOI":"10.2337\/dc15-1990","volume":"39","author":"D Control","year":"2016","unstructured":"Control, D., Interventions, C. T. E., o., D. & Group, C. S. Intensive diabetes treatment and cardiovascular outcomes in type 1 diabetes: the DCCT\/EDIC study 30-year follow-up. Diabetes Care  39, 686\u2013693 (2016).","journal-title":"Diabetes Care"},{"key":"7204_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1900\/RDS.2019.15.1","volume":"15","author":"J Khateeb","year":"2019","unstructured":"Khateeb, J., Fuchs, E. & Khamaisi, M. Diabetes and lung disease: An underestimated relationship. Rev. Diabet. Stud. 15, 1\u201315 (2019).","journal-title":"Rev. Diabet. Stud."},{"key":"7204_CR42","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1900\/RDS.2012.9.23","volume":"9","author":"D Pitocco","year":"2012","unstructured":"Pitocco, D. et al. The diabetic lung\u2014a new target organ? Rev. Diabet. Stud. 9, 23\u201335. https:\/\/doi.org\/10.1900\/RDS.2012.9.23 (2012).","journal-title":"Rev. Diabet. Stud."},{"key":"7204_CR43","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1002\/dmrr.1175","volume":"27","author":"J Yang","year":"2011","unstructured":"Yang, J., Xue, Q., Miao, L. & Cai, L. Pulmonary fibrosis: A possible diabetic complication. Diabetes Metab. Res. Rev. 27, 311\u2013317. https:\/\/doi.org\/10.1002\/dmrr.1175 (2011).","journal-title":"Diabetes Metab. Res. Rev."},{"key":"7204_CR44","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1164\/arrd.1976.113.1.37","volume":"113","author":"MR Schuyler","year":"1976","unstructured":"Schuyler, M. R., Niewoehner, D. E., Inkley, S. R. & Kohn, R. Abnormal lung elasticity in juvenile diabetes mellitus. Am. Rev. Respir Dis. 113, 37\u201341. https:\/\/doi.org\/10.1164\/arrd.1976.113.1.37 (1976).","journal-title":"Am. Rev. Respir Dis."},{"key":"7204_CR45","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1164\/arrd.1983.128.1.125","volume":"128","author":"K Kida","year":"1983","unstructured":"Kida, K., Utsuyama, M., Takizawa, T. & Thurlbeck, W. M. Changes in lung morphologic features and elasticity caused by streptozotocin-induced diabetes mellitus in growing rats. Am. Rev. Respir Dis. 128, 125\u2013131. https:\/\/doi.org\/10.1164\/arrd.1983.128.1.125 (1983).","journal-title":"Am. Rev. Respir Dis."},{"key":"7204_CR46","doi-asserted-by":"publisher","unstructured":"Atta, A. H. et al. Cucumis sativus and Cucurbita maxima extract attenuate diabetes-induced hepatic and pancreatic injury in a rat model. J. Physiol. Pharmacol. 71 https:\/\/doi.org\/10.26402\/jpp.2020.4.06 (2020).","DOI":"10.26402\/jpp.2020.4.06"},{"key":"7204_CR47","doi-asserted-by":"publisher","first-page":"50","DOI":"10.2337\/diab.47.1.50","volume":"47","author":"Z Wang","year":"1998","unstructured":"Wang, Z. & Gleichmann, H. GLUT2 in pancreatic islets: Crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice. Diabetes 47, 50\u201356. https:\/\/doi.org\/10.2337\/diab.47.1.50 (1998).","journal-title":"Diabetes"},{"key":"7204_CR48","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.biopha.2017.05.068","volume":"92","author":"U Muruganathan","year":"2017","unstructured":"Muruganathan, U., Srinivasan, S. & Vinothkumar, V. Antidiabetogenic efficiency of menthol, improves glucose homeostasis and attenuates pancreatic beta-cell apoptosis in streptozotocin-nicotinamide induced experimental rats through ameliorating glucose metabolic enzymes. Biomed. Pharmacother.  92, 229\u2013239. https:\/\/doi.org\/10.1016\/j.biopha.2017.05.068 (2017).","journal-title":"Biomed. Pharmacother"},{"key":"7204_CR49","doi-asserted-by":"publisher","first-page":"537","DOI":"10.33549\/physiolres.930111","volume":"50","author":"T Szkudelski","year":"2001","unstructured":"Szkudelski, T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol. Res. 50, 537\u2013546 (2001).","journal-title":"Physiol. Res."},{"key":"7204_CR50","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1007\/s001250051564","volume":"43","author":"M Elsner","year":"2000","unstructured":"Elsner, M., Guldbakke, B., Tiedge, M., Munday, R. & Lenzen, S. Relative importance of transport and alkylation for pancreatic beta-cell toxicity of streptozotocin. Diabetologia 43, 1528\u20131533. https:\/\/doi.org\/10.1007\/s001250051564 (2000).","journal-title":"Diabetologia"},{"key":"7204_CR51","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/2251-6581-12-60","volume":"12","author":"CO Eleazu","year":"2013","unstructured":"Eleazu, C. O., Eleazu, K. C., Chukwuma, S. & Essien, U. N. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J. Diabetes Metab. Disord. 12, 60. https:\/\/doi.org\/10.1186\/2251-6581-12-60 (2013).","journal-title":"J. Diabetes Metab. Disord."},{"key":"7204_CR52","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1152\/physrev.00034.2006","volume":"87","author":"JJ Holst","year":"2007","unstructured":"Holst, J. J. The physiology of glucagon-like peptide 1. Physiol. Rev. 87, 1409\u20131439. https:\/\/doi.org\/10.1152\/physrev.00034.2006 (2007).","journal-title":"Physiol. Rev."},{"key":"7204_CR53","doi-asserted-by":"publisher","first-page":"175498","DOI":"10.1016\/j.ejphar.2023.175498","volume":"941","author":"RZ ElGamal","year":"2023","unstructured":"ElGamal, R. Z., Tadros, M. G. & Menze, E. T. Linagliptin counteracts rotenone\u2019s toxicity in non-diabetic rat model of parkinson\u2019s disease: Insights into the neuroprotective roles of DJ-1, SIRT-1\/Nrf-2 and implications of HIF1-alpha. Eur. J. Pharmacol. 941, 175498. https:\/\/doi.org\/10.1016\/j.ejphar.2023.175498 (2023).","journal-title":"Eur. J. Pharmacol."},{"key":"7204_CR54","doi-asserted-by":"publisher","first-page":"541","DOI":"10.21608\/ejchem.2022.106453.5015","volume":"65","author":"A A.Sedik","year":"2022","unstructured":"A.Sedik, A. Modulation activity of vildagliptin on hepatic complications and lipoprotein abnormalities associated with insulin resistance in rats. Egypt. J. Chem. 65, 541\u2013547. https:\/\/doi.org\/10.21608\/ejchem.2022.106453.5015 (2022).","journal-title":"Egypt. J. Chem."},{"key":"7204_CR55","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1111\/j.1463-1326.2011.01414.x","volume":"13","author":"B Ahren","year":"2011","unstructured":"Ahren, B. et al. Mechanisms of action of the dipeptidyl peptidase-4 inhibitor vildagliptin in humans. Diabetes Obes. Metab. 13, 775\u2013783. https:\/\/doi.org\/10.1111\/j.1463-1326.2011.01414.x (2011).","journal-title":"Diabetes Obes. Metab."},{"key":"7204_CR56","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.arcmed.2009.09.005","volume":"40","author":"HY Jin","year":"2009","unstructured":"Jin, H. Y., Liu, W. J., Park, J. H., Baek, H. S. & Park, T. S. Effect of dipeptidyl peptidase-IV (DPP-IV) inhibitor (vildagliptin) on peripheral nerves in streptozotocin-induced diabetic rats. Arch. Med. Res. 40, 536\u2013544. https:\/\/doi.org\/10.1016\/j.arcmed.2009.09.005 (2009).","journal-title":"Arch. Med. Res."},{"key":"7204_CR57","doi-asserted-by":"publisher","unstructured":"Bhandari, U., Jain, N. & Pillai, K. K. Further studies on antioxidant potential and protection of pancreatic beta-cells by Embelia ribes in experimental diabetes. Exp. Diabetes Res. 1580. https:\/\/doi.org\/10.1155\/2007\/15803 (2007).","DOI":"10.1155\/2007\/15803"},{"key":"7204_CR58","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/s0008-6363(00)00097-3","volume":"47","author":"B Halliwell","year":"2000","unstructured":"Halliwell, B. Lipid peroxidation, antioxidants and cardiovascular disease: How should we move forward? Cardiovasc. Res. 47, 410\u2013418. https:\/\/doi.org\/10.1016\/s0008-6363(00)00097-3 (2000).","journal-title":"Cardiovasc. Res."},{"key":"7204_CR59","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1007\/s12010-021-03753-z","volume":"194","author":"AG Aggul","year":"2022","unstructured":"Aggul, A. G., Demir, G. M. & Gulaboglu, M. Ethanol extract of Myrtle (Myrtus communis L.) berries as a remedy for streptozotocin-induced oxidative stress in rats. Appl. Biochem. Biotechnol. 194, 1645\u20131658. https:\/\/doi.org\/10.1007\/s12010-021-03753-z (2022).","journal-title":"Appl. Biochem. Biotechnol."},{"key":"7204_CR60","doi-asserted-by":"publisher","first-page":"110635","DOI":"10.1016\/j.colsurfb.2019.110635","volume":"185","author":"W Bei","year":"2020","unstructured":"Bei, W., Jing, L. & Chen, N. Cardio protective role of wogonin loaded nanoparticle against isoproterenol induced myocardial infarction by moderating oxidative stress and inflammation. Colloids Surf. B Biointerfaces. 185, 110635. https:\/\/doi.org\/10.1016\/j.colsurfb.2019.110635 (2020).","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"7204_CR61","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.ijcard.2012.04.087","volume":"158","author":"S Maeda","year":"2012","unstructured":"Maeda, S., Matsui, T. & Yamagishi, S. Vildagliptin inhibits oxidative stress and vascular damage in streptozotocin-induced diabetic rats. Int. J. Cardiol. 158, 171\u2013173. https:\/\/doi.org\/10.1016\/j.ijcard.2012.04.087 (2012).","journal-title":"Int. J. Cardiol."},{"key":"7204_CR62","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ejphar.2007.08.001","volume":"576","author":"A Kuhad","year":"2007","unstructured":"Kuhad, A. & Chopra, K. Curcumin attenuates diabetic encephalopathy in rats: Behavioral and biochemical evidences. Eur. J. Pharmacol. 576, 34\u201342. https:\/\/doi.org\/10.1016\/j.ejphar.2007.08.001 (2007).","journal-title":"Eur. J. Pharmacol."},{"key":"7204_CR63","doi-asserted-by":"publisher","unstructured":"Muriach, M., Flores-Bellver, M., Romero, F. J. & Barcia, J. M. Diabetes and the brain: oxidative stress, inflammation, and autophagy. Oxid. Med. Cell Longev. 102158. https:\/\/doi.org\/10.1155\/2014\/102158 (2014).","DOI":"10.1155\/2014\/102158"},{"key":"7204_CR64","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.3390\/biom5031266","volume":"5","author":"M Schuliga","year":"2015","unstructured":"Schuliga, M. NF-kappaB signaling in chronic inflammatory airway disease. Biomolecules 5, 1266\u20131283. https:\/\/doi.org\/10.3390\/biom5031266 (2015).","journal-title":"Biomolecules"},{"key":"7204_CR65","doi-asserted-by":"publisher","first-page":"913","DOI":"10.18632\/aging.100390","volume":"3","author":"S Vaughan","year":"2011","unstructured":"Vaughan, S. & Jat, P. S. Deciphering the role of nuclear factor-kappaB in cellular senescence. Aging 3, 913\u2013919. https:\/\/doi.org\/10.18632\/aging.100390 (2011).","journal-title":"Aging"},{"key":"7204_CR66","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1136\/thx.53.7.601","volume":"53","author":"I Rahman","year":"1998","unstructured":"Rahman, I. & MacNee, W. Role of transcription factors in inflammatory lung diseases. Thorax 53, 601\u2013612. https:\/\/doi.org\/10.1136\/thx.53.7.601 (1998).","journal-title":"Thorax"},{"key":"7204_CR67","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1042\/BJ20050078","volume":"389","author":"G Hughes","year":"2005","unstructured":"Hughes, G., Murphy, M. P. & Ledgerwood, E. C. Mitochondrial reactive oxygen species regulate the temporal activation of nuclear factor kappab to modulate tumour necrosis factor-induced apoptosis: Evidence from mitochondria-targeted antioxidants. Biochem. J. 389, 83\u201389. https:\/\/doi.org\/10.1042\/BJ20050078 (2005).","journal-title":"Biochem. J."},{"key":"7204_CR68","doi-asserted-by":"publisher","first-page":"359","DOI":"10.52547\/ibj.25.5.359","volume":"25","author":"Z Shahab-Movahed","year":"2021","unstructured":"Shahab-Movahed, Z., Majd, A., Siasi Torbati, E. & Zeinali, S. Distal renal tubular acidosis in an Iranian patient with hereditary spherocytosis. Iran. Biomed. J. 25, 359\u2013367. https:\/\/doi.org\/10.52547\/ibj.25.5.359 (2021).","journal-title":"Iran. Biomed. J."},{"key":"7204_CR69","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1538\/expanim.20-0123","volume":"70","author":"W Wang","year":"2021","unstructured":"Wang, W. et al. Effect of low-dose ethanol on NLRP3 inflammasome in diabetes-induced lung injury. Exp. Anim. 70, 364\u2013371. https:\/\/doi.org\/10.1538\/expanim.20-0123 (2021).","journal-title":"Exp. Anim."},{"key":"7204_CR70","doi-asserted-by":"publisher","first-page":"115674","DOI":"10.1016\/j.taap.2021.115674","volume":"429","author":"X Tian","year":"2021","unstructured":"Tian, X. et al. -)-Epicatechin ameliorates cigarette smoke-induced lung inflammation via inhibiting ROS\/NLRP3 inflammasome pathway in rats with COPD. Toxicol. Appl. Pharmacol. 429, 115674. https:\/\/doi.org\/10.1016\/j.taap.2021.115674 (2021).","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"7204_CR71","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1016\/j.biopha.2018.07.063","volume":"106","author":"J Wang","year":"2018","unstructured":"Wang, J., Wang, L., Zhou, J., Qin, A. & Chen, Z. The protective effect of formononetin on cognitive impairment in streptozotocin (STZ)-induced diabetic mice. Biomed. Pharmacother.  106, 1250\u20131257. https:\/\/doi.org\/10.1016\/j.biopha.2018.07.063 (2018).","journal-title":"Biomed. Pharmacother."},{"key":"7204_CR72","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/jcsm.12662","volume":"12","author":"C Aluganti Narasimhulu","year":"2021","unstructured":"Aluganti Narasimhulu, C. & Singla, D. K. Amelioration of diabetes-induced inflammation mediated pyroptosis, sarcopenia, and adverse muscle remodelling by bone morphogenetic protein-7. J. Cachexia Sarcopenia Muscle 12, 403\u2013420. https:\/\/doi.org\/10.1002\/jcsm.12662 (2021).","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"7204_CR73","doi-asserted-by":"publisher","first-page":"112684","DOI":"10.1016\/j.bbr.2020.112684","volume":"391","author":"DX Li","year":"2020","unstructured":"Li, D. X. et al. NLRP3 inflammasome-dependent pyroptosis and apoptosis in hippocampus neurons mediates depressive-like behavior in diabetic mice. Behav. Brain Res. 391, 112684. https:\/\/doi.org\/10.1016\/j.bbr.2020.112684 (2020).","journal-title":"Behav. Brain Res."},{"key":"7204_CR74","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.4103\/1673-5374.360242","volume":"18","author":"HY Yu","year":"2023","unstructured":"Yu, H. Y. et al. Exendin-4 and linagliptin attenuate neuroinflammation in a mouse model of parkinson\u2019s disease. Neural Regen Res. 18, 1818\u20131826. https:\/\/doi.org\/10.4103\/1673-5374.360242 (2023).","journal-title":"Neural Regen Res."},{"key":"7204_CR75","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1080\/21691401.2019.1578783","volume":"47","author":"Y Qi","year":"2019","unstructured":"Qi, Y., Du, X., Yao, X. & Zhao, Y. Vildagliptin inhibits high free fatty acid (FFA)-induced NLRP3 inflammasome activation in endothelial cells. Artif. Cells Nanomed. Biotechnol. 47, 1067\u20131074. https:\/\/doi.org\/10.1080\/21691401.2019.1578783 (2019).","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"7204_CR76","doi-asserted-by":"publisher","first-page":"548","DOI":"10.3390\/antiox12030548","volume":"12","author":"FS Bezerra","year":"2023","unstructured":"Bezerra, F. S. et al. Oxidative stress and inflammation in acute and chronic lung injuries. Antioxidants (Basel) 12, 548. https:\/\/doi.org\/10.3390\/antiox12030548 (2023).","journal-title":"Antioxidants (Basel)"},{"key":"7204_CR77","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1111\/j.1365-2249.2010.04175.x","volume":"161","author":"B Z\u2019Graggen","year":"2010","unstructured":"Z\u2019Graggen, B. Acute lung injury: Apoptosis in effector and target cells of the upper and lower airway compartment. Clin. Exp. Immunol. 161, 324\u2013331. https:\/\/doi.org\/10.1111\/j.1365-2249.2010.04175.x (2010).","journal-title":"Clin. Exp. Immunol."},{"key":"7204_CR78","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.trsl.2013.10.002","volume":"163","author":"CF Chian","year":"2014","unstructured":"Chian, C. F., Chiang, C. H., Chuang, C. H. & Liu, S. L. Inhibitor of nuclear factor-kappaB, SN50, attenuates lipopolysaccharide-induced lung injury in an isolated and perfused rat lung model. Transl Res. 163, 211\u2013220. https:\/\/doi.org\/10.1016\/j.trsl.2013.10.002 (2014).","journal-title":"Transl Res."},{"key":"7204_CR79","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.2337\/db07-0136","volume":"56","author":"A Vella","year":"2007","unstructured":"Vella, A. et al. Effects of dipeptidyl peptidase-4 Inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes. Diabetes 56, 1475\u20131480. https:\/\/doi.org\/10.2337\/db07-0136 (2007).","journal-title":"Diabetes"}],"updated-by":[{"DOI":"10.1038\/s41598-025-19552-z","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07204-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07204-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07204-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T22:02:49Z","timestamp":1758319369000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07204-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,25]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["7204"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-07204-1","relation":{"correction":[{"id-type":"doi","id":"10.1038\/s41598-025-19552-z","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,25]]},"assertion":[{"value":"29 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2025","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-025-19552-z","URL":"https:\/\/doi.org\/10.1038\/s41598-025-19552-z","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The National Institutes of Health\u2019s Guide for Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978) and the National Research Center\u2019s Medical Research Ethics Committee\u2019s approval for the use of animal subjects (Approval no. 130601102) guidelines were followed in all experimental procedures. All methods were performed in accordance with the relevant guidelines and regulations. The present study is reported in accordance with ARRIVE guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}],"article-number":"20292"}}