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FSHW | 黄大茶高效缓解2型糖尿病“三多一高”典型病症并预防糖尿病肾病

Introduction

静态生活方式和能量摄入超标是导致肥胖相关疾病，包括2型糖尿病的主要因素。多尿、多饮、多食和高血糖是糖尿病典型病症。肝脏和肾脏是参与维持机体糖稳态的主要器官。抑制肝糖生成、促进肾糖排泄是临床治疗糖尿病的重要手段。糖尿病肾病是糖尿病主要并发症之一，也是糖尿病患者末期肾衰竭的主要诱因。有效控制血糖并降低高血糖引起的渗透性利尿可预防糖尿病肾病的发生和发展。

黄大茶为粗老叶夏秋茶，主产于安徽霍山。前期研究表明，经拉老火特殊工艺制备的黄大茶对α-葡萄糖苷酶抑制效果显著提升，且黄大茶相比其它茶类能够显著降低高脂饮食诱导的肥胖模型小鼠的血糖水平。为进一步探究黄大茶的降血糖潜力，河南农业大学青年教师赵广山、暨南大学任哲*和蒲含林*副研究员、罗格斯大学Chung S. Yang教授*等考察了黄大茶对STZ联合高脂饮食诱导的2型糖尿病小鼠的作用效果，并进一步阐述其缓解糖尿病典型病症和糖尿病肾病的分子机制。

Results and discussion

如图1所示，黄大茶剂量依赖（1/100,1/50，m/V）的缓解了2型糖尿病小鼠“三多一高”典型病症，减轻了胰岛素抵抗、葡萄糖耐受和非酒精性脂肪肝（NAFLD），并降低了血脂积累。分子层面，黄大茶显著下调了肝脏糖脂生成关键基因（ACCβ、Fasn、SCD1、G6Pc、PEPCK、FOXO1-α、TXNIP）mRNA表达水平和蛋白（SREBP-1）表达水平，以及FBP酶活力水平，并下调了脂肪氧化相关蛋白（CPT-1α、PPARα）表达水平。

图1 黄大茶对2型糖尿病小鼠典型病症和非酒精性脂肪肝的影响

图2 黄大茶对2型糖尿病小鼠肝脏糖脂代谢关键基因mRNA、蛋白表达水平和酶活力的调节作用

此外，作者发现黄大茶（1/50，m/V）可有效预防2型糖尿病小鼠肾小球系膜扩张和肾脏纤维化，机制涉及黄大茶显著下调2型糖尿病小鼠肾病关键诱导因子PKC-β2、NLRP3和膜PKC-α、糖基化AQP2蛋白表达水平。阳性药达格列净呈现出显著的降血糖效果，对糖尿病小鼠的摄食量和饮水量无显著影响，但显著增加了糖尿病小鼠排尿量并加剧了渗透性利尿引起的肾脏纤维化。

图3 黄大茶对2型糖尿病小鼠糖尿病肾病的预防效果和调节机制

Conclusion

黄大茶可通过调节糖脂生成和脂肪酸氧化代谢通路，抑制肝脏糖脂生成并促进脂肪酸代谢，并通过改善葡萄糖耐受和胰岛素抵抗，缓解2型糖尿病小鼠非酒精性脂肪肝和高脂血症，同时强效改善糖尿病“三多一高”典型病症。此外，黄大茶可通过降低血糖减少高血糖引起的渗透性利尿，并下调肾病关键诱导因子（PKC-β2、NLRP3和膜PKC-α、糖基化AQP2）蛋白表达水平，从而预防糖尿病肾病。总之，研究结果提示黄大茶有希望成为2型糖尿病患者膳食补充剂，用于预防和辅助改善2型糖尿病及其并发症。

作者简介

第一作者

赵广山，博士，河南农业大学青年教师，任Frontiers in Nutrition期刊客座编委。主要研究方向为食品营养与安全、茶叶精深加工与健康。主持及参与省部级项目2项，参与国家级项目1项。已发表SCI学术论文13篇，包括Molecular Nutrition and Food Research、Free Radical Biology and Medicine、Food Science and Human Wellness、Frontiers in Nutrition等具有国际影响力的学术期刊。

通信作者

Chung S. Yang，博士、美国罗格斯大学终身教授，世界著名营养与肿瘤预防学专家，首位“柯拉易讲座教授”，全球高被引科学家，已发表SCI学术论文500余篇，包括Nature、Nature Reviews Cancer、PNAS、JACS、Cancer Research、Clinical Cancer Research、Trends in Food Science & Technology、Critical Reviews in Food Science and Nutrition、Food Chemistry、Molecular Nutrition and Food Research等著名国际期刊。

任哲，博士，暨南大学副研究员，硕士生导师，广东省生物物理学会理事，广东省药学会生物工程制药专委会专家组副组长。承担国家级重大科研项目1项（十二五“863”项目）和省级科研项目6项。作为核心成员参与国家级重大科研项目3项。广东省科技进步奖二等奖1项。授权发明专利2项，申报发明专利10余项。已发表SCI、EI等学术论文40余篇。

Alleviating effects and mechanisms of action of large-leaf yellow tea drinking on diabetes and diabetic nephropathy in mice

Guangshan Zhao^a,b,1, Jianyuan Teng^b,1, Ruixia Dong^c,d,1, Qiuyan Ban^e, Lian Yang^f, Kang Du^f, Yifei Wang^b, Hanlin Pu^b,*, Chung S. Yang^g,h,*, Zhe Ren^b,^*

^a Innovation Team of Food Nutrition and Safety Control, College of Food Science & Technology, Henan Agricultural University, Zhengzhou 450002, China

^b Biology Postdoctoral Research Station, Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China

^cCollege of Horticulture, Jinling Institute of Technology, Nanjing 211169, China

^dDepartment of Forestry and Technology, Lishui Vocational and Technical College, Lishui 323000, China

^e Department of Tea Science, College of Horticulture, Henan Agricultural University, Zhengzhou 450002, China

^f Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China

^g Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway 08901, USA

^h International Joint Research Laboratory of Tea Chemistry and Health Effects, Anhui Agricultural University, Hefei 230036, China

¹ Both authors contributed equally.

*Corresponding authors.

Abstract

Our previous study found that large-leaf yellow tea (LYT) had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the present study further investigated the preventive effects and mechanisms of action of LYT administration on diabetes and diabetic nephropathy in high-fat diet plus streptozotocin-induced diabetic mice. Results showed that LYT infusions (1/100 and 1/50, m/V) as drinking fluid for 4 weeks reduced diabetic polydipsia and polyuria, enhanced glucose tolerance and insulin sensitivity, and lowered fasting blood glucose level. The underlying mechanisms involve downregulation of gluconeogenesis (lower protein levels of TXNIP and FBP and enzyme activity of FBP), upregulation of lipid catabolism (higher protein levels of CPT-1α and PPARα), downregulation of lipogenesis (lower protein level of SREBP-1), and modification of the structure and abundance of gut microbiota to modulate metabolic homeostasis. Moreover, LYT administration prevented diabetic nephropathy, possibly due to reduced glucose-caused osmotic diuresis and lowered levels of renal PKC-β2, NLRP3 as well as membrane PKC-α, AQP2 and glycosylated AQP2 proteins. Taken together, LYT exhibits the activities in alleviating diabetic symptoms, ameliorating glucose and lipid dysmetabolism and fatty liver, and preventing diabetic nephropathy in diabetic mice. These activities may be explored for the prevention and treatment of diabetes in humans.

Reference:

ZHAO G S, TENG J Y, DONG R X, et al. Alleviating effects and mechanisms of action of large-leaf yellow tea drinking on diabetes and diabetic nephropathy in mice[J]. Food Science and Human Wellness, 2023, 12(5): 1660-1673. DOI:10.1016/j.fshw.2023.02.023.