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Gastric inflammation is common and usually severe in patients with type 2 diabetes mellitus (T2DM). Evidence suggests protease-activated receptors (PARs) are a link between inflammation and gastrointestinal dysfunction. Given that magnesium (Mg2+) deficiency is a highly prevalent condition in T2DM patients, we assessed the therapeutic role of Mg2+ on the factors involved in gastric inflammation in T2DM. Methods. A rat model of T2DM gastropathy was established using a long-term high-fat diet\u2009+\u2009a low dose of streptozocin. Twenty-four rats were divided into control, T2DM , T2DM\u2009+\u2009insulin (positive control), and T2DM\u2009+\u2009Mg2+ groups. At the end of 2-month therapies, changes in the expression of gastric trypsin-1, PAR1, PAR2, PAR3, PI3K\/Akt, and COX-2 proteins were measured by western blot. Hematoxylin and eosin and Masson\u2019s trichrome staining were used to detect gastric mucosal injury and fibrosis. Results. The expression of trypsin-1, PAR1, PAR2, PAR3, and COX-2 increased in diabetes, and Mg2+\/insulin treatment strongly decreased their expression. The PI3K\/p-Akt significantly decreased in T2DM, and treatment with Mg2+\/insulin improved PI3K in T2DM rats. Staining of the gastric antrum tissue of the insulin\/Mg2+-treated T2DM rats showed a significantly minimal mucosal and fibrotic injury compared with those of rats from the T2DM group. Conclusion. Mg2+ supplement, comparable to insulin, via decreasing PARs expression, mitigating COX-2 activity, and decreasing collagen deposition could exert a potent gastroprotective effect against inflammation, ulcer, and fibrotic development in T2DM patients.<\/jats:p>","DOI":"10.1155\/2023\/5703718","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T21:20:08Z","timestamp":1684272008000},"page":"1-11","source":"Crossref","is-referenced-by-count":0,"title":["Changes in Protease-Activated Receptor and Trypsin-1 Expression Are Involved in the Therapeutic Effect of Mg2+ Supplementation in Type 2 Diabetes-Induced Gastric Injury in Male Adult Rats"],"prefix":"10.1155","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7298-0189","authenticated-orcid":true,"given":"Nasrin","family":"Mehranfard","sequence":"first","affiliation":[{"name":"Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0831-6811","authenticated-orcid":true,"given":"Hossein","family":"Rezazadeh","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3071-0647","authenticated-orcid":true,"given":"Nepton","family":"Soltani","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azadesadat Hosseini","family":"Dastgerdi","sequence":"additional","affiliation":[{"name":"Department of Preclinical Medicine, School of Medicine, Najafabad Branch, Islamic Azad University, Isfahan, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahtab","family":"Ghanbari Rad","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5414-9594","authenticated-orcid":true,"given":"Maedeh","family":"Ghasemi","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026647417465"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.5056\/JNM18162"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/J.MPMED.2019.04.011"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.3390\/NU13020320"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1007\/S10534-021-00328-7"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/J.ABB.2006.03.031"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S136742"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1053\/J.GASTRO.2011.01.046"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1007\/S00535-006-1909-8"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021036601462"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1111\/J.1365-2982.2009.01336.X"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00115.2019"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.4239\/WJD.V6.I10.1152"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0B013E31820CA695"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1186\/S12959-019-0194-8"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00717"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3130496"},{"issue":"10","key":"18","first-page":"4512","article-title":"Protease activated receptor 2 in diabetic nephropathy: a double edged sword","volume":"9","author":"M. 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