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Pharmacol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Telmisartan is an angiotensin receptor blocker (ARB) that specifically blocks angiotensin II type-1 receptors (AT1R). Telmisartan has been proven to have antidiabetic effects via a variety of mechanisms, and it can be utilized in some diabetic patients due to its dual benefit for hypertensive patients with type 2 DM (T2DM) and when the other oral antidiabetic medications are intolerable or contraindicated. However, its precise underlying hypoglycemic mechanism is still obscure.<\/jats:p><jats:p><jats:bold>Aim of work:<\/jats:bold> We sought to establish a link between telmisartan administration and myostatin expression in skeletal muscles of T2DM rat model as a potential hypoglycemic mechanism of telmisartan.<\/jats:p><jats:p><jats:bold>Materials and Methods:<\/jats:bold> 32 male albino rats were included in the study; 8 rats served as controls (group I). T2DM was inducted in the other 24 rats, which were then randomly subdivided into 3 groups (8 in each): (group II) the Diabetic group and (groups III and IV) which were treated with either telmisartan (8\u00a0mg\/kg\/day) or metformin (250\u00a0mg\/kg\/day) respectively via oral gavage for a 4-week period.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Telmisartan administration resulted in a significant improvement in OGTT, HOMA-IR, glucose uptake, and muscle mass\/body ratios in Telmisartan group as compared to Diabetic group (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). Additionally, telmisartan induced a significant boost in adiponectin and IL-10 serum levels with a substantial drop in TNF-\u03b1 and IL-6 levels in Telmisartan group compared to diabetic rats (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). Moreover, telmisartan significantly boosted SOD and GSH, and decreased MDA levels in the skeletal muscles of telmisartan group. Furthermore, a significant downregulation of myostatin and upregulation of insulin receptor, IRS-1, and IRS-3 genes in the skeletal muscles of Telmisartan group were also detected. Histologically, telmisartan attenuated the morphological damage in the skeletal muscle fibers compared to diabetic rats, as evidenced by a considerable decrease in the collagen deposition area percentage and a reduction in NF-kB expression in the muscle tissues of group III.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Telmisartan administration dramatically reduced myostatin and NF-kB expressions in skeletal muscles, which improved insulin resistance and glucose uptake in these muscles, highlighting a novel antidiabetic mechanism of telmisartan in treating T2DM.<\/jats:p>","DOI":"10.3389\/fphar.2023.1228525","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T16:26:04Z","timestamp":1690561564000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Telmisartan versus metformin in downregulating myostatin gene expression and enhancing insulin sensitivity in the skeletal muscles of type 2 diabetic rat model"],"prefix":"10.3389","volume":"14","author":[{"given":"Ahmed","family":"Abd-Eltawab Tammam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed Y.","family":"Rizg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Fakhry Boushra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Alhelf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Alissa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada F.","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada","family":"Nady Ouais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled M.","family":"Hosny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala M.","family":"Alkhalidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Magdy","family":"Elebiary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.21608\/mjcu.2018.58062","article-title":"Olive leaf extract and a-tocopherol combination therapy attenuates doxorubicin induced cardiotoxicity in rats","volume":"86","author":"Alaa","year":"2018","journal-title":"Med. 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