Scopoletin protects against methylglyoxal-induced hyperglycemia and insulin resistance mediated by suppression of advanced glycation endproducts (AGEs) generation and anti-glycation.
Scopoletin protects against methylglyoxal-induced hyperglycemia and insulin resistance mediated by suppression of advanced glycation endproducts (AGEs) generation and anti-glycation.
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DOI：
10.3390/molecules20022786
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发表时间：
2015-02-09
期刊：
影响因子：
--
通讯作者：
Cheng AS
中科院分区：
文献类型：
--
作者：
Chang WC;Wu SC;Xu KD;Liao BC;Wu JF;Cheng AS
最近，几种类型的食物和饮料，包括咖啡，奶油和蛋糕，已被发现导致血浆中的甲基乙二醛（MG）水平高，从而引起营养和健康问题。MG可通过核因子-红细胞2相关因子2（Nrf 2）的正向调节，由肝脏中的II相酶代谢。在这项研究中，我们研究了东莨菪碱（SP）的能力，以防止MG诱导的高血糖和胰岛素抵抗。近年来，研究发现SP是一种过氧化物酶体增殖物激活受体-γ激活剂，可提高胰岛素敏感性。我们研究了口服SP对MG治疗的Wistar大鼠2型糖尿病的代谢、生化和分子异常特征的影响，以了解东莨菪碱对糖尿病保护的潜在机制。结果提示，SP通过Ser 40磷酸化激活Nrf 2，使MG代谢为d-乳酸，抑制AGEs的生成，从而减少AGEs在MG诱导大鼠肝脏中的蓄积。以这种方式，SP改善了口服葡萄糖耐量试验和血脂异常的结果。此外，SP还增加了MG处理的FL 83 B肝细胞中葡萄糖转运蛋白-2的血浆易位，并促进胰岛素处理引起的Akt磷酸化。与此相反，SP有效地抑制蛋白酪氨酸磷酸酶1B（PTP 1B）的表达，从而减轻胰岛素抵抗。这些结果表明，SP作为一种抗糖化和抗糖尿病剂，因此具有治疗潜力的预防糖尿病。
Recently, several types of foods and drinks, including coffee, cream, and cake, have been found to result in high methylglyoxal (MG) levels in the plasma, thus causing both nutritional and health concerns. MG can be metabolized by phase-II enzymes in liver through the positive regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2). In this study, we investigated the ability of scopoletin (SP) to protect against MG-induced hyperglycemia and insulin resistance. Recently, SP was shown to be a peroxisome proliferator-activated receptor-γ activator to elevate insulin sensitivity. We investigated the effects of oral administration of SP on the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats to understand the potential mechanism of scopoletin for diabetes protection. Our results suggested that SP activated Nrf2 by Ser40 phosphorylation, resulting in the metabolism of MG into d-lactic acid and the inhibition of AGEs generation, which reduced the accumulation of AGEs in the livers of MG-induced rats. In this manner, SP improved the results of the oral glucose tolerance test and dyslipidemia. Moreover, SP also increased the plasma translocation of glucose transporter-2 and promoted Akt phosphorylation caused by insulin treatment in MG-treated FL83B hepatocytes. In contrast, SP effectively suppressed protein tyrosine phosphatase 1B (PTP1B) expression, thereby alleviating insulin resistance. These findings suggest that SP acts as an anti-glycation and anti-diabetic agent, and thus has therapeutic potential for the prevention of diabetes.
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DOI：
10.1081/jlc-100101786
发表时间：
1999-01-01
影响因子：
1.3
作者：
Barros, A;Rodrigues, JA;Oliva-Teles, MT
通讯作者：
Oliva-Teles, MT
影响因子：
--
作者：
Kim, Junghyun;Kim, Chan-Sik;Kim, Jin Sook
通讯作者：
Kim, Jin Sook
影响因子：
6.7
作者：
Lee, Jun;Kim, Nan Hee;Kim, Jin Sook
通讯作者：
Kim, Jin Sook
影响因子：
7.3
作者：
Dhar, Arti;Dhar, Indu;Wu, Lingyun
通讯作者：
Wu, Lingyun
影响因子：
4.1
作者：
DEREVEL, G;BERTRAND, A
通讯作者：
BERTRAND, A