高血糖会导致线粒体氧化应激增加,细胞内炎症信号异常激活,并介导多种功能障碍。覆盆子酮(RK)是一种芳香族酚类化合物,存在于许多植物中,可帮助减肥、恢复受损的葡萄糖耐量,并具有抗氧化特性。在我们的研究中,覆盆子酮可大大预防链脲佐菌素(STZ)诱导的高血糖斑马鱼模型中胰岛、大脑和其他组织因高血糖造成的损伤。RK 还能恢复体重、胰岛素水平和食物摄入量指标。通过转录组分析,我们发现服用 RK 能显著减少 STZ 诱导的胰岛素合成和胰腺分泌,并能改变蛋白质和碳水化合物的代谢。代谢组学分析结果显示,RK还能预防STZ诱导的代谢紊乱,如腺苷和鞘脂代谢。代谢组和转录组数据的整合分析以及关键代谢调控基因(glut1、glut2、ctrb1、cka、ck、pklr)的qRT-PCR验证证实,嘌呤通路是富集程度最高的代谢通路,其中代谢物的积累和基因表达水平在RK处理后呈现一致的变化规律。我们的研究为了解 RK 的降血糖机制提供了一个新的视角,可能有助于利用斑马鱼高血糖模型研究降血糖药物的作用模式。
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Study on the signaling pathways involved in the anti-hyperglycemic effect of raspberry ketone on zebrafish using integrative transcriptome and metabolome analyses†
Hyperglycemia leads to increased oxidative stress in mitochondria, an abnormal activation of intracellular inflammatory signals, and mediate multiple dysfunctions. Raspberry ketone (RK) is an aromatic phenolic compound found in many plants and could contribute to weight loss, restore impaired glucose tolerance, and has antioxidant properties. In our investigation, RK could greatly prevent islet, brain and other tissue damage caused by hyperglycemia in a zebrafish model with streptozotocin (STZ)-induced hyperglycemia. Body weight, insulin level, and food intake indexes were also restored by RK. Using transcriptome profiling, we found that RK administration could significantly attenuate STZ-induced insulin synthesis and pancreatic secretion as well as alter protein and carbohydrate metabolism. Metabolomics analysis results showed that RK could also prevent STZ-induced metabolic disorders, such as adenosine and sphingolipid metabolism. Integrative analysis of metabolome and transcriptome data and qRT-PCR validation of key metabolic regulatory genes (glut1, glut2, ctrb1, ccka, gck, pklr) confirmed that the purine pathway was the most enriched metabolic pathway, in which both metabolite accumulation and gene expression levels showed consistent change patterns upon RK treatment. Our study provides a new perspective for understanding the hypoglycemic mechanism of RK and may be helpful for investigating the modes of action of hypoglycemic drugs using the zebrafish hyperglycemia model.
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网址: 利用转录组和代谢组的综合分析,研究覆盆子酮对斑马鱼的降血糖作用所涉及的 https://m.trfsz.com/newsview1309574.html