Abd-Eltawab Tammam Ahmed, Rizg Waleed Y, Fakhry Boushra Amy, Alhelf Maha, Alissa Mohammed, Soliman Ghada F, Nady Ouais Ghada, Hosny Khaled M, Alkhalidi Hala M, Elebiary Ahmed Magdy
Medical Physiology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.
Center of Innovation in Personalized Medicine (CIPM), 3D Bioprinting Unit, King Abdulaziz University, Jeddah, Saudi Arabia.
Front Pharmacol. 2023 Jul 28;14:1228525. doi: 10.3389/fphar.2023.1228525. eCollection 2023.
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. 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. 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 mg/kg/day) or metformin (250 mg/kg/day) respectively via oral gavage for a 4-week period. 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 ( < 0.05). Additionally, telmisartan induced a significant boost in adiponectin and IL-10 serum levels with a substantial drop in TNF-α and IL-6 levels in Telmisartan group compared to diabetic rats ( < 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. 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.
替米沙坦是一种血管紧张素受体阻滞剂（ARB），它特异性地阻断血管紧张素II 1型受体（AT1R）。替米沙坦已被证明通过多种机制具有抗糖尿病作用，并且由于它对2型糖尿病（T2DM）高血压患者具有双重益处，以及在其他口服抗糖尿病药物不耐受或禁忌时，它可用于一些糖尿病患者。然而，其确切的潜在降糖机制仍不清楚。我们试图在T2DM大鼠模型的骨骼肌中建立替米沙坦给药与肌肉生长抑制素表达之间的联系，作为替米沙坦潜在的降糖机制。该研究纳入了32只雄性白化大鼠；8只大鼠作为对照组（I组）。在其他24只大鼠中诱导T2DM，然后将它们随机分为3组（每组8只）：（II组）糖尿病组和（III组和IV组），分别通过口服灌胃给予替米沙坦（8毫克/千克/天）或二甲双胍（250毫克/千克/天），为期4周。与糖尿病组相比，替米沙坦组给予替米沙坦后，口服葡萄糖耐量试验（OGTT）、稳态模型评估胰岛素抵抗（HOMA-IR）、葡萄糖摄取以及肌肉质量/体重比均有显著改善（P<0.05）。此外，与糖尿病大鼠相比，替米沙坦组替米沙坦可使脂联素和白细胞介素-10血清水平显著升高，肿瘤坏死因子-α和白细胞介素-6水平大幅下降（P<0.05）。此外，替米沙坦组骨骼肌中的超氧化物歧化酶（SOD）和谷胱甘肽（GSH）显著升高，丙二醛（MDA）水平降低。此外，还检测到替米沙坦组骨骼肌中肌肉生长抑制素显著下调，胰岛素受体、胰岛素受体底物-1（IRS-1）和胰岛素受体底物-3（IRS-3）基因上调。组织学上，与糖尿病大鼠相比，替米沙坦减轻了骨骼肌纤维的形态损伤，III组肌肉组织中胶原沉积面积百分比显著降低以及核因子-κB（NF-κB）表达减少证明了这一点。替米沙坦给药显著降低了骨骼肌中肌肉生长抑制素和NF-κB的表达，改善了这些肌肉的胰岛素抵抗和葡萄糖摄取，突出了替米沙坦治疗T2DM的一种新的抗糖尿病机制。
