Crateva unilocularis Buch-Ham has traditionally been used in Nepal for the treatment and prevention of diabetes. However, scientific verification through studies on the preventive effect of C. unilocularis on diabetes has not been done properly. In this study we investigated the effect of C. unilocularis leaf extract (CULE) on glucose uptake and insulin resistance. The effect of CULE on glucose uptake in an in vivo system was measured using zebrafish. In the cell-free system, enzymes activities related to diabetes were measured. Moreover, in the cell-cultured system, RIN-m5F pancreatic beta cells, 3T3-L1 adipocytes, and L6 myotubes were used to measure the effect of CULE on insulin secretion and glucose metabolism. CULE effectively enhanced glucose uptake in zebrafish larvae, and inhibited the activity of dipeptidyl peptidase-IV (DPP-IV) and protein tyrosine phosphatase-1B (PTP-1B) enzymes related to insulin secretion and insulin signaling activation. Also, CULE significantly increased insulin secretion with suppression of NO production in RIN-m5F pancreatic beta cells. In L6 myotubes and TNF-α-induced insulin resistance model of 3T3-L1 adipocytes, CULE significantly increased glucose uptake and immunofluorescence staining of glucose transporter (GLUT)4 protein. Furthermore, the regulatory response of glucose metabolism by CULE was a close correlation with the activation of insulin signaling (IRβ, PI3K, AKT) and 5′-AMP-activated protein kinase (AMPK)α and the reduction of p38 mitogen-activated protein kinase (MAPK) in TNF-α-induced insulin resistance model of 3T3-L1 adipocytes. Thus, our results suggest that CULE may act as a potential agent for the prevention and treatment of metabolic syndrome associated with type 2 diabetes.

中文翻译：

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Crateva unilocularis Buch-Ham 叶提取物通过在体外和体内调节胰岛素分泌和敏感性来改善葡萄糖代谢

Crateva unilocularis Buch-Ham 传统上在尼泊尔用于治疗和预防糖尿病。然而，通过研究单房假单胞菌对糖尿病的预防作用的科学验证尚未得到妥善完成。在这项研究中，我们研究了 C. unilocularis 叶提取物 (CULE) 对葡萄糖摄取和胰岛素抵抗的影响。使用斑马鱼测量了 CULE 对体内系统中葡萄糖摄取的影响。在无细胞系统中，测量了与糖尿病相关的酶活性。此外，在细胞培养系统中，RIN-m5F 胰腺 β 细胞、3T3-L1 脂肪细胞和 L6 肌管用于测量 CULE 对胰岛素分泌和葡萄糖代谢的影响。CULE 有效增强斑马鱼幼虫的葡萄糖摄取，并抑制与胰岛素分泌和胰岛素信号激活相关的二肽基肽酶-IV (DPP-IV) 和蛋白酪氨酸磷酸酶-1B (PTP-1B) 酶的活性。此外，CULE 显着增加胰岛素分泌，抑制 RIN-m5F 胰腺 β 细胞中 NO 的产生。在 L6 肌管和 TNF-α 诱导的 3T3-L1 脂肪细胞胰岛素抵抗模型中，CULE 显着增加葡萄糖摄取和葡萄糖转运蛋白 (GLUT)4 蛋白的免疫荧光染色。此外，CULE 对葡萄糖代谢的调节反应与胰岛素信号传导（IRβ​​、PI3K、AKT）和 5'-AMP 活化蛋白激酶（AMPK）α 的激活以及 p38 丝裂原活化蛋白激酶的减少密切相关。 (MAPK) 在 TNF-α 诱导的 3T3-L1 脂肪细胞胰岛素抵抗模型中。因此，