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茶黄素通过调节 INSR/PI3K-Akt/GSK-3 通路和肠道微生物群减轻 GK 大鼠的糖尿病症状。

Theaflavins mitigate diabetic symptoms in GK rats by modulating the INSR/PI3K-Akt/GSK-3 pathway and intestinal microbiota.

机构信息

Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, Hunan, China; School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China.

Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, Hunan, China.

出版信息

Int J Biol Macromol. 2024 Oct;277(Pt 2):134331. doi: 10.1016/j.ijbiomac.2024.134331. Epub 2024 Jul 31.

Abstract

Dietary management and interventions are crucial in the clinical management of diabetes. Numerous active dietary components in black tea have demonstrated positive effects on blood glucose levels and metabolic functions. However, limited research has explored the potential of theaflavins (TF), polyphenols in black tea, for diabetes management. In this study, high-purity TF was administered to Goto-Kakizaki (GK) diabetic model rats for four weeks to investigate its impact on diabetic pathology and analyze the underlying mechanisms through liver transcriptomics, hepatocyte metabolomics, and gut microbiome analysis. The findings indicated that continuous administration of TF (100 mg/kg) significantly suppressed blood glucose levels, reduced insulin resistance, and decreased the expression of oxidative stress indicators and inflammatory factors in GK rats. Further analysis revealed that TF might alleviate insulin resistance by improving hepatic glycogen conversion and reducing hepatic lipid deposition through modulation of key pathways, such as peroxisome proliferator-activated receptors and PI3K/AKT/GSK-3 pathways within the liver, thereby ameliorating diabetic symptoms. Additionally, TF intake facilitated the restoration of the intestinal microbial community structure by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. It also reduced endotoxin lipopolysaccharide production, thereby lowering the chances of insulin resistance development and enhancing its efficacy in regulating blood glucose levels. These findings offer a novel perspective on the potential of black tea and its active constituents to prevent and treat diabetes and other metabolic disorders, providing valuable references for identifying and applying active dietary components from tea.

摘要

饮食管理和干预在糖尿病的临床管理中至关重要。红茶中许多具有活性的饮食成分已被证明对血糖水平和代谢功能有积极影响。然而,对于红茶中的茶黄素(TF)等多酚类物质在糖尿病管理中的应用,研究还很有限。在这项研究中,高纯度 TF 被给予 Goto-Kakizaki(GK)糖尿病模型大鼠,持续给药四周,以研究其对糖尿病病理的影响,并通过肝转录组学、肝细胞代谢组学和肠道微生物组分析来分析潜在机制。研究结果表明,连续给予 TF(100mg/kg)可显著抑制血糖水平,降低胰岛素抵抗,并降低 GK 大鼠的氧化应激指标和炎症因子的表达。进一步分析表明,TF 可能通过改善肝糖原转化和减少肝脂质沉积来缓解胰岛素抵抗,这是通过调节肝脏内的关键途径(如过氧化物酶体增殖物激活受体和 PI3K/AKT/GSK-3 途径)实现的,从而改善糖尿病症状。此外,TF 的摄入有助于通过减少有害细菌的丰度和增加有益细菌的丰度来恢复肠道微生物群落结构。它还减少了内毒素脂多糖的产生,从而降低了胰岛素抵抗发展的可能性,并增强了其调节血糖水平的功效。这些发现为红茶及其活性成分预防和治疗糖尿病和其他代谢紊乱提供了新的视角,为从茶中识别和应用活性饮食成分提供了有价值的参考。

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