咖啡酸及肉桂酸減輕小鼠肝臟細胞 (FL83B) 胰島素阻抗及改善碳水化合物代謝之研究

Alleviation of Insulin Resistance and Improvement in Carbohydrate Metabolism in Insulin Resistant Mouse Liver FL83B Cells by Caffeic acid and Cinnamic acid

黃大維(Da-Wei Huang)

指導教授 ： 吳瑞碧

共同指導教授 ： 沈賜川

國立臺灣大學/生物資源暨農學院/食品科技研究所/博士(2010年)

https://doi.org/10.6342/NTU.2010.02526

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的慢性疾病。約 95％ 的糖尿病患者屬於第二型糖尿病，發生原因主要為胰島素作用缺失及體內細胞對胰島素無法引起正常之反應而導致高血糖症。咖啡酸及肉桂酸為多種水果、蔬菜及咖啡中常存在的兩種酚酸，近來已有許多研究在評估此兩酚酸抗高血糖之活性。
本實驗以 TNF-α 誘導小鼠肝臟 FL83B 細胞產生胰島素阻抗，再評估咖啡酸及肉桂酸之增加阻抗細胞葡萄糖攝入及改善醣類代謝。實驗中以葡萄糖攝入實驗評估兩種酚酸降血糖之效果，並分析胰島素訊息蛋白、肝醣合成相關酵素以及糖質新生酵素的表現，以解釋胰島素阻抗 FL83B 細胞中葡萄糖攝入增加與肝醣合成之改善。
於抗高血糖效果實驗中發現，咖啡酸及肉桂酸會促進胰島素受器 (Insulin receptor, IR) 磷酸化及增加胰島素訊息相關蛋白包括磷酸肌醇激酶(phosphatidylinositol-3 kinase, PI3K)、肝醣合成酶 (glycogen synthase, GS) 及葡萄糖轉運蛋白 (glucose transporter-2, GLUT-2) 的表現。於改善醣類代謝結果顯示，此兩種酚酸會增加胰島素阻抗細胞中葡萄糖激酶 (Glucokinase, GK)，但會減少肝醣合成酶激酶 (glycogen synthase kinase, GSK)、肝醣合成酶 serine 磷酸、肝細胞核因子 (hepatic nuclear factor-4, HNF-4) 及磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carbooxykinase, PEPCK) 的表現。根據以上之結果推測，咖啡酸及肉桂酸可以藉由改善胰島素阻抗 FL83B 細胞對胰島素的敏感度而促進細胞葡萄糖攝入及改善醣類代謝。

關鍵字

糖尿病 ； 咖啡酸 ； 肉桂酸 ； 葡萄糖攝入 ； 肝醣合成 ； 胰島素阻抗

並列摘要

Diabetes mellitus (DM) is a chronic disease associated with carbohydrate metabolism and caused by a deficiency in insulin secretion or by the ineffectiveness in insulin action. About 95% of the diabetic incidences belong to type 2 diabetes, of which the main cause of hyperglycemia is the ineffectiveness in insulin action or the inability to induce a normal response to insulin in the cells. Two phenolic acids, caffeic acid and cinnamic acid, are commonly present in fruits, vegetables, and coffee. Anti-hyperglycemic activity has become a focus in recent studies on these two phenolic acids.
The present study investigated the effect of the two phenolics on enhancing glucose uptake and ameliorating carbohydrate metabolism in TNF-α-induced insulin resistant mouse liver FL83B cells.The uptake test of 2-[1-14C ] deoxy-D-glucose in insulin resistant FL83B cells was performed to evaluate the hypoglycemic effect. The expressions of insulin signal proteins, glycogen synthesis associated enzymes and the enzymes of gluconeogenesis were analyzed to elucidate the enhancement on glucose uptake and the restoration on glycogen synthesis in insulin resistant FL83B cells by the phenolic acids..
In the results of antihyperglycemic effect, the two phenolic acids promote insulin receptor tyrosyl phosphorylation, up-regulat the expression of insulin signal associated proteins, including insulin receptor, phosphatidylinositol-3 kinase (PI3K), glycogen synthase (GS), and glucose transporter-2 (GLUT-2). The results of amelioration on carbohydrate metabolism revealed that the two phenolic acids increase the expression of Glucokinase (GK), while decrease the expression of glycogen synthase kinase (GSK), Ser-641 phosphorylation of GS, hepatic nuclear factor-4 (HNF-4), and phosphoenolpyruvate carbooxykinase (PEPCK) in the resistant cells.
In conclusion, we speculate that caffeic acid and cinnamic acid may improve glucose uptake and ameliorate carbohydrate metabolism by restoring isulin sensitivity in insulin resistant FL83B cells. These two phenolic acids may restore glycogen synthesis, promote glucose uptake into cells, inhibit gluconeogehesis to decrease glucose formation, and result in the alleviation of insulin resistance in cells as the consequence.

並列關鍵字

Diabetes mellitus ； caffeic acid ； cinnamic acid ； glucose uptake ； glycogen synthesis ； insulin resistance

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