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Protocatechuic acid improves hepatic insulin resistance and restores vascular oxidative status in type-2 diabetic rats
Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2020-12-28 , DOI: 10.1016/j.etap.2020.103577
Marwa E. Abdelmageed , George S.G. Shehatou , Ghada M. Suddek , Hatem A. Salem

This work explored influences of protocatechuic acid (PCA) on type 2 diabetes (T2D)-associated hepatic insulin resistance and other metabolic, hepatic and vascular irregularities using the rat model of high fat diet (HFD)+high fructose+low dose streptozotocin (STZ).

Twenty-four male Wister rats were used. Twelve rats were ad libitum supplied with HFD and high fructose drinking water (25 % w/v) for 60 days. On day 30, they received a single injection of STZ (35 mg/kg, i.p). On day 32, they were divided into two subgroups (n = 6/each): T2D + PCA, received PCA (100 mg/kg/day, orally) and T2D, received PCA vehicle till the end of experiment. Rats provided with regular diet and fructose-free drinking water, with or without PCA treatment, served as PCA and control groups (n = 6/each), respectively.

PCA treatment significantly reduced the elevated levels of fasting glycemia and insulin, AUCOGTT, AUCITT, and HOMA-IR index, while it boosted HOMA-β and insulinogenic index values in T2D rats. PCA ameliorated serum lipid levels and hepatic function parameters and mitigated hepatosteatosis in T2D rats. Mechanistically, PCA mitigated hepatic lipid peroxidation and restored reduced glutathione (GSH) and superoxide dismutase (SOD) to near-normal levels. Moreover, PCA enhanced hepatic protein levels of P-AKTser473 and hepatic mRNA expression of insulin receptor substrate 1 (IRS1), phosphatidylinositol 3 kinase (PI3K)-p85 and AKT2.

Furthermore, PCA ameliorated aortic oxidative stress in T2D rats, possibly via reducing serum levels of advanced glycation end products (AGEs) and diminishing vascular expression of RAGE and NOX4 mRNA.

Collectively, PCA may improve hepatic insulin resistance and vascular oxidative status by modulating IRS1/PI3K/AKT2 and AGE-RAGE-NOX4 pathways, respectively.



中文翻译:

原儿茶酸改善2型糖尿病大鼠的肝胰岛素抵抗并恢复血管氧化状态

这项工作使用高脂饮食(HFD)+高果糖+低剂量链脲佐菌素(STZ)大鼠模型探索了原儿茶酸(PCA)对2型糖尿病(T2D)相关的肝胰岛素抵抗以及其他代谢,肝和血管异常的影响)。

使用了24只雄性Wister大鼠。随意给12只大鼠提供HFD和高果糖饮用水(25%w / v),持续60天。在第30天,他们接受了STZ单次注射(35 mg / kg,腹膜内)。在第32天,将它们分为两个亚组(n = 6 /每个):T2D + PCA,接受PCA(100 mg / kg /天,口服)和T2D,接受PCA载体,直到实验结束。提供有规则饮食和无果糖饮用水的大鼠,不论是否接受PCA治疗,分别作为PCA对照组(n = 6 /每组)。

PCA治疗可显着降低空腹血糖和胰岛素,AUC OGTT,AUC ITT和HOMA-IR指数的升高水平,同时可提高T2D大鼠的HOMA-β和胰岛素原性指数值。PCA改善了T2D大鼠的血脂水平和肝功能参数,减轻了肝脂肪变性。从机理上讲,五氯苯甲醚可减轻肝脏脂质过氧化作用,并将还原型谷胱甘肽(GSH)和超氧化物歧化酶(SOD)恢复至接近正常水平。此外,PCA增强了P-AKT ser473的肝蛋白水平以及胰岛素受体底物1(IRS1),磷脂酰肌醇3激酶(PI3K)-p85和AKT2的肝mRNA表达。

此外,PCA可能通过降低晚期糖基化终产物(AGEs)的血清水平并减少RAGE和NOX4 mRNA的血管表达来改善T2D大鼠的主动脉氧化应激。

总体而言,PCA可能分别通过调节IRS1 / PI3K / AKT2和AGE-RAGE-NOX4途径来改善肝胰岛素抵抗和血管氧化状态。

更新日期:2021-01-06
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