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曲克芦丁对高脂和蔗糖诱导的2型糖尿病成年雄性大鼠腓肠肌胰岛素信号分子的影响。

Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat.

作者信息

Sampath Sathish, Karundevi Balasubramanian

机构信息

Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, India.

出版信息

Mol Cell Biochem. 2014 Oct;395(1-2):11-27. doi: 10.1007/s11010-014-2107-2. Epub 2014 Jun 1.

DOI:10.1007/s11010-014-2107-2
PMID:24880482
Abstract

Troxerutin is a trihydroxyethylated derivative of the flavonoid, rutin. It has been reported to possess the hepatoprotective, nephroprotective, antioxidant, anti-inflammatory, and antihyperlipidemic activities. Troxerutin treatment reduced the blood glucose and glycosylated hemoglobin levels in high-cholesterol-induced insulin-resistant mice and in type-2 diabetic patients. However, the mechanism by which it exhibits antidiabetic property was unknown. Therefore, the present study was designed to evaluate the effect of troxerutin on insulin signaling molecules in gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic rats. Wistar male albino rats were selected and divided into five groups. Group I: Control. Group II: High fat and sucrose-induced type-2 diabetic rats. Group III: Type-2 diabetic rats treated with troxerutin (150 mg/kg body weight/day orally). Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg body weight/day orally). Group V: Normal rats treated with troxerutin (150 mg/kg body weight/day orally). After 30 days of treatment, fasting blood glucose, oral glucose tolerance, serum lipid profile, and the levels of insulin signaling molecules, glycogen, glucose uptake, and oxidation in gastrocnemius muscle were assessed. Diabetic rats showed impairment in insulin signaling molecules (IR, p-IRS-1(Tyr632), p-Akt(Ser473), β-arrestin-2, c-Src, p-AS160(Thr642), and GLUT4 proteins), glycogen concentration, glucose uptake, and oxidation. Oral administration of troxerutin showed near normal levels of blood glucose, serum insulin, lipid profile, and insulin signaling molecules as well as GLUT4 proteins in type-2 diabetic rats. It is concluded from the present study that troxerutin may play a significant role in the management of type-2 diabetes mellitus, by improving the insulin signaling molecules and glucose utilization in the skeletal muscle.

摘要

曲克芦丁是类黄酮芦丁的三羟乙基化衍生物。据报道,它具有肝脏保护、肾脏保护、抗氧化、抗炎和抗高血脂活性。曲克芦丁治疗可降低高胆固醇诱导的胰岛素抵抗小鼠和2型糖尿病患者的血糖和糖化血红蛋白水平。然而,其发挥抗糖尿病特性的机制尚不清楚。因此,本研究旨在评估曲克芦丁对高脂肪和蔗糖诱导的2型糖尿病大鼠腓肠肌中胰岛素信号分子的影响。选用雄性Wistar白化大鼠,分为五组。第一组:对照组。第二组:高脂肪和蔗糖诱导的2型糖尿病大鼠。第三组:用曲克芦丁(150毫克/千克体重/天,口服)治疗的2型糖尿病大鼠。第四组:用二甲双胍(50毫克/千克体重/天,口服)治疗的2型糖尿病大鼠。第五组:用曲克芦丁(150毫克/千克体重/天,口服)治疗的正常大鼠。治疗30天后,评估空腹血糖、口服葡萄糖耐量、血清脂质谱以及腓肠肌中胰岛素信号分子、糖原、葡萄糖摄取和氧化的水平。糖尿病大鼠的胰岛素信号分子(胰岛素受体、p-胰岛素受体底物-1(酪氨酸632)、p-Akt(丝氨酸473)、β-抑制蛋白-2、c-Src、p-AS160(苏氨酸642)和葡萄糖转运蛋白4蛋白)、糖原浓度、葡萄糖摄取和氧化均受损。口服曲克芦丁可使2型糖尿病大鼠的血糖、血清胰岛素、脂质谱、胰岛素信号分子以及葡萄糖转运蛋白4蛋白水平接近正常。本研究得出结论,曲克芦丁可能通过改善骨骼肌中的胰岛素信号分子和葡萄糖利用,在2型糖尿病的管理中发挥重要作用。

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