首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Time-dependent therapeutic roles of nitazoxanide on high-fat diet/streptozotocin-induced diabetes in rats: effects on hepatic peroxisome proliferator-activated receptor-gamma receptors
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Time-dependent therapeutic roles of nitazoxanide on high-fat diet/streptozotocin-induced diabetes in rats: effects on hepatic peroxisome proliferator-activated receptor-gamma receptors

机译:尼硝唑的时间依赖治疗作用对大鼠高脂肪饮食/链脲佐菌素诱导的糖尿病:对肝过氧缺血剂活化受体 - γ受体的影响

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Targeting peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is an approved strategy in facing insulin resistance (IR) for diabetes mellitus (DM) type 2. The PPAR-gamma modulators display improvements in the insulin-sensitizing and adverse effects of the traditional thiazolidinediones. Nitazoxanide (NTZ) is proposed as a PPAR-gamma receptor ligand with agonistic post-transcriptional effects. Currently, NTZ antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozotocin rat model of type 2 diabetes was explored. Diabetic adult male Wistar rats were treated orally with either PIO (2.7 mg.kg(-1.)day(-1)) or NTZ (200 mg.kg(-1).day(-1)) for 14, 21, and 28 days. Body masses, fasting blood glucose, IR, lipid profiles, and liver and kidney functions of rats were assayed. Hepatic glucose metabolism and PPAR-gamma protein expression levels as well as hepatic, pancreatic, muscular, and renal histopathology were evaluated. Significant time-dependent euglycemic and insulin-sensitizing effects with preservation of liver and kidney functions were offered by NTZ. Higher hepatic levels of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase enzymes and PPAR-gamma protein expressions were acquired by NTZ and PIO, respectively. NTZ could be considered an oral therapeutic strategy for DM type 2. Further systematic NTZ/PPAR-gamma receptor subtype molecular activations are recommended. Simultaneous use of NTZ with other approved antidiabetics should be explored.
机译:靶向过氧化物体增殖物激活的受体-γ(PPAR-GAMMA)是面对胰岛素抵抗(IR)的批准策略,用于糖尿病(DM)型2. PPAR-GAMMA调制器显示出胰岛素敏化和不利影响的改善传统的噻唑烷。奈唑烷(NTZ)作为PPAR-Gamma受体配体,具有激动的转录作用。目前,探讨了NTZ抗糖尿病酮(PIO)在2型糖尿病中的高脂饮食/链霉型大鼠模型中。用PIO(2.7mg.kg(-1)天(-1))或NTZ(200 mg.kg(-1),21)口服(2.7mg.kg(-1)天(-1))或NTZ治疗糖尿病成年雄性Wistar大鼠和28天。测定体积,空腹血糖,IR,脂质谱和肝脏和肝肾功能的测定。评估肝葡萄糖代谢和PPAR-Gamma蛋白表达水平以及肝,胰腺,肌肉和肾组织病理学。 NTZ提供了与保存肝脏和肾功能保存的显着时间依赖性的神经血糖和胰岛素致敏作用。 NTZ和PIO分别通过NTZ和PIO获得较高的葡萄糖-6-磷酸酶和葡萄糖-6-磷酸脱氢酶和PPAR-Gamma蛋白表达的肝脏水平。 NTZ可以被认为是DM型的口服治疗策略2.建议进一步系统的NTZ / PPAR-Gamma受体亚型分子激活。应探讨与其他批准的反对派的同时使用NTZ。

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