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槲皮素和黄秋葵对糖尿病大鼠(高脂饮食/链脲佐菌素诱导)脂质代谢和血糖的影响:通过AMPK-α途径

Effect of quercetin and Abelmoschus esculentus (L.) Moench on lipids metabolism and blood glucose through AMPK-α in diabetic rats (HFD/STZ).

作者信息

Nasrollahi Zohreh, ShahaniPour Kahin, Monajemi Ramesh, Ahadi Ali Mohammad

机构信息

Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Isfahan, Iran.

Department of Biology, Falavarjan Branch, Islamic Azad University, Isfahan, Iran.

出版信息

J Food Biochem. 2022 Dec;46(12):e14506. doi: 10.1111/jfbc.14506. Epub 2022 Nov 12.

Abstract

Phosphoenolpyruvate carboxykinase (PEPCK) is a key enzyme in the glyconeogenesis pathway. The AMP-activated protein kinase alpha (AMPK-α) pathway regulates PEPCK, which itself is activated by the AMP/ATP ratio and liver kinase B1 (KB1). The Abelmoschus esculentus (L.) Moench (okra) plant contains a large amount of quercetin that can function as an agonist or an antagonist. The aim of this study was to examine the effects of quercetin flavonoid and A. esculentus extract on the level of AMPK-α expression and associated metabolic pathways. The findings demonstrate that metformin, quercetin, and okra extract may significantly raise AMPK-α levels while significantly lowering PEPCK and hormone-sensitive lipase (HSL) levels, in addition to improving glucose and lipid profiles. By stimulating KB1, these substances increased AMPK-α activation. Additionally, AMPK-α activation improved insulin resistance and Glucose transporter type 4 (GLUT4) gene expression levels. Since AMPK-α maintains energy balance and its activity has not been reported to be inhibited so far, it could be a potent therapeutic target. PRACTICAL APPLICATIONS: The development of effective AMPK-α agonists and antagonists holds promise for the treatment of metabolic disorders like diabetes. Dietary polyphenols are a valuable source for developing new drugs. However, due to the lack of understanding of the underlying mechanisms of their effect on cells, their use in the treatment of diabetes is controversial. In addition to chemicals that have medicinal benefits, chemists are searching for less harmful substances. Using plants containing bioactive chemicals for this purpose can be a good alternative to chemical drugs.

摘要

磷酸烯醇式丙酮酸羧激酶(PEPCK)是糖异生途径中的关键酶。AMP激活的蛋白激酶α(AMPK-α)途径调节PEPCK,而AMPK-α本身由AMP/ATP比值和肝激酶B1(LKB1)激活。黄秋葵(Abelmoschus esculentus (L.) Moench)植物含有大量槲皮素,其可作为激动剂或拮抗剂发挥作用。本研究的目的是检测槲皮素类黄酮和黄秋葵提取物对AMPK-α表达水平及相关代谢途径的影响。研究结果表明,二甲双胍、槲皮素和秋葵提取物除了可改善血糖和血脂水平外,还可能显著提高AMPK-α水平,同时显著降低PEPCK和激素敏感性脂肪酶(HSL)水平。通过刺激LKB1,这些物质增加了AMPK-α的激活。此外,AMPK-α的激活改善了胰岛素抵抗和4型葡萄糖转运蛋白(GLUT4)基因表达水平。由于AMPK-α维持能量平衡,且目前尚未有其活性受到抑制的报道,因此它可能是一个有效的治疗靶点。实际应用:开发有效的AMPK-α激动剂和拮抗剂有望用于治疗糖尿病等代谢紊乱疾病。膳食多酚是开发新药的宝贵来源。然而,由于对其作用于细胞的潜在机制缺乏了解,它们在糖尿病治疗中的应用存在争议。除了具有药用价值的化学物质外,化学家们正在寻找危害较小的物质。为此使用含有生物活性化学物质的植物可能是化学药物的一个很好的替代品。

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