粉紅種蓮霧幼果水萃物減輕以腫瘤壞死因子 (TNF-α) 處理之小鼠肝臟細胞 (FL83B) 胰島素阻抗及改善醣類代謝之研究

Alleviation of Insulin Resistance and Improvement in Carbohydrate Metabolism in TNF-α Treated Mouse Liver FL83B Cells by Pink Wax Apple Fruit Water Extract

張巧俐(Chiao-Li Chang)

指導教授 ： 吳瑞碧

國立臺灣大學/生物資源暨農學院/食品科技研究所/碩士(2011年)

https://doi.org/10.6342/NTU.2011.02843

摘要

糖尿病為胰島素分泌缺乏或胰島素作用缺失所導致的一種醣類代謝慢性疾病。現今糖尿病患者中約 95% 屬於第二型糖尿病，其發病主因之一推測為生理發炎反應造成胰島素功能缺失或體內細胞與胰島素無法正常反應而導致高血糖現象。目前已有文獻證實桃金孃科 (Myrtaceae family) 植物具有抗糖尿病作用，本研究以食用桃金孃科植物中的粉紅種蓮霧幼果為材料，經萃取分離純化後篩選出最具提升葡萄糖攝入能力之水萃物高極性區分物 (FPWE) 做為測試樣品。首先探討FPWE對腫瘤壞死因子 (Tumor necrosis factor-α, TNF-α) 誘發胰島素阻抗之小鼠肝臟細胞 (FL83B) 之胰島素訊息傳遞蛋白質及醣解酵素的表現；接著探討其FPWE對胰島素阻抗之小鼠肝臟細胞 (FL83B) 發炎反應因子表現之影響。
結果顯示，在胰島素阻抗方面， FPWE可提升以TNF-α 處理之小鼠肝臟細胞 (FL83B) 胰島素受器 (insulin receptor, IR) 磷酸化、胰島素受器受質 (insulin receptor substrate-1, IRS-1)表現量及促進胰島素訊息相關蛋白包括磷酸肌醇激酶 (phosphatidylinositol-3 kinase, PI3K)、serine/threonine protein kinase (Akt)、肝醣合成酶 (glycogen synthase, GS) 及葡萄糖轉運蛋白 (glucose transporter-2, GLUT-2) 的活化。在醣解代謝方面，FPWE 可增加胰島素阻抗細胞中六碳醣激酶 (hexokinase, HXK)、葡萄糖六磷酸酶 (glucose-6-phosphate dehydrogenase, G6PDase)、果醣磷酸激酶 (phosphofructokinase, PFK)、醛縮酶 (aldolase) 之表現。在抗發炎反應方面，FPWE 會降低因TNF-α 而活化之JNK、ERK、NF-κB及COX-2等相關蛋白質之表現。根據上述結果推測，粉紅種蓮霧幼果水萃物之高極性區分物可能藉由降低胰島素阻抗小鼠肝臟細胞 FL83B 之發炎反應與提升其對胰島素的敏感度，進而改善細胞葡萄糖攝入之能力。

關鍵字

糖尿病 ； 胰島素阻抗 ； 粉紅種蓮霧幼果區分物 ； 醣類代謝 ； 發炎反應

並列摘要

Diabetes mellitus (DM) is a chronic disease associated with carbohydrate metabolism and is caused by a deficiency in insulin secretion or by the ineffectiveness in insulin action. Around 95% of the diabetic incidences belong to type 2 diabetes, of which, the main cause is the ineffectiveness in insulin action. Literatures confirmed the anti-diabetic effect of Myrtaceae plants. In a previous study, we found the high polarity fraction from pink wax apple aqueous extract (FPWE) may improve glucose uptake in insulin resistant mouse hepatocytes. In the present study, mouse FL83B hepatocytes were treated with tumor necrosis factor-α (TNF-α) for induction of insulin resistance. FPWE was used for investigating the expressions of insulin signal protein and glycolysis associated protein in insulin resistant hepatocytes. The effect of FPWE on inflammation in insulin resistant FL83B was also evaluated.
The results show that FPWE promotes the phosphorylation of insulin receptor tyrosyl and the expressions of insulin receptor substrate-1 and the insulin signal associated proteins, including insulin receptor, phosphatidylinositol-3 kinase (PI3K), Akt/PKB, glycogen synthase (GS) and glucose transporter-2 (GLUT-2). In the aspect of carbohydrate metabolism, the results revealed that FPWE increases the expression of hexokinase (HXK), glucose-6-phosphate dehydrogenase (G6PDase), phosphofructokinase (PFK) and aldolase. In the respect of inflammation, FPWE decreases phosphorylation of JNK and the protein expressions of ERK, NF-κB and COX-2 in the resistant FL83B cells.
In conclusion, FPWE may improve the glucose uptake in insulin resistant mouse FL83B hepatocytes via the reduction of inflammation and the incensement of insulin sensitivity.

並列關鍵字

diabetes mellitus ； insulin resistance ； young pink wax apple fruit aqueous extract ； carbonhydrate metabolism ； inflammation

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