糖尿病患者中約有95%屬於第二型糖尿病，其主因多為胰島素阻抗而導致高血糖之情況。已有許多文獻證實桃金孃科 ( Myrtaceae family ) 植物具抗糖尿病之效用，本研究室先前以桃金孃科植物中的蓮霧幼果萃取物為材料，經分離、純化、鑑定與胰島素阻抗細胞模式試驗後，確認具有抗糖尿病潛力的活性化合物 Vescalagin 與 Gallic acid 。本研究進一步進行動物實驗，探討 Vescalagin與 Gallic acid 對以高果糖飼料誘導之高血糖、高胰島素血症糖尿病前期大鼠肝臟組織中胰島素阻抗與醣類代謝之影響，並探討其對改善糖尿病前期大鼠體內抗發炎與抗氧化之效果。
結果顯示，Vescalagin與 Gallic acid具有明顯降低高果糖飼料誘導糖尿病大鼠血糖之效果。西方墨點法分析結果顯示，在胰島素訊息傳遞部分， Vescalagin與 Gallic acid 可以增加胰島素受器( insulin receptor，IR )、胰島素受器受質( insulin receptor substrate-1，IRS-1 ) 、磷酸肌醇3激酶 ( Phosphatidylinositol-3 kinase，PI3K ) 、 AKT/蛋白激酶B ( AKT/Protein kinase B，AKT/PKB )、葡萄糖轉運蛋白2 ( glucose transporter-2，GLUT2 )等蛋白質之表現量。在醣類代謝部分， Vescalagin 與 Gallic acid 可以增加糖解作用酵素，包括 Hexokinase 、 Phosphofructokinase 與 Aldolase 之蛋白質表現量；肝醣合成酵素，如Glycogen synthase 之表現亦增加；然而糖質新生作用酵素，如 Frucotse-1,6-bisphosphatase 之表現會降低；而在磷酸五碳糖途徑酵素，如Glucose-6-phosphate dehydrogenase 之表現亦會增加。在抗發炎反應部分， Vescalagin 與 Gallic acid 降低了 NF-κB 路徑中的 NF-κB、COX-2、MCP-1 與 ICAM-1等發炎反應相關蛋白質之表現量。在抗氧化部分， Vescalagin 與 Gallic acid 則是增加了 SOD、Catalase 與 Glutathione peroxidase 酵素之活性，並且降低了體內脂質過氧化之程度。根據上述結果推測，蓮霧幼果分離物─ Vescalagin與 Gallic acid 可能藉由降低發炎反應及氧化壓力，因而改善高果糖飼料誘發之糖尿病前期大鼠胰島素阻抗現象，並調節醣類的正常代謝與利用。

Around 95% of the diabetic incidences belong to Type 2 diabetes mellitus (Type 2 DM). Type 2 DM is characterized as the insulin resistance and leaded to hyperglycemia. Previous studies have been confirmed the anti-diabetic effect of Myrtaceae family plants. Our laboratory previously found that vescalagin and gallic acid from wax apple, belongs to Maytaceae family plant and is one of important economic fruits in Taiwan and Oriental, fruit possessed potential on anti-diabetic in insulin resistance cell model. In the present study, we investigated the effect of vescalagin and gallic acid from pink wax apple on ameliorating carbohydrate metabolism, insulin resistance, anti-inflammation and antioxidation in vivo in high fructose diet (HFD)-induced prediabetic rats.
The results show that vescalagin and gallic acid from pink wax apple significantly decrease blood glucose level in HFD-induced prediabetic rats. The Western blot analysis reveals vescalagin and gallic acid promote the expression of insulin signaling-associated protein, including insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase (PI3K), AKT/Protein kinase B (AKT/ PKB) and glucose transporter-2 (GLUT2) in HFD rats. In the aspect of carbohydrate metabolism in liver, the results revealed that vescalagin and gallic acid increases the protein expression of glycolysis enzymes, including hexokinase, phosphofructokinase and aldolase; increases the protein expression of glycogen synthase; decreases the protein expressions of frucotse-1,6-bisphosphatase; increases the protein expression of glucose-6-phosphate dehydrogenase. Vescalagin and gallic acid decreased the expression of inflammatory factors, such as NF-κB, COX-2, MCP-1 and ICAM-1 I D in HFD rats. Vescalagin and gallic acid also increased the activity of anti-oxidative enzymes, including SOD, catalase and glutathione peroxidase, and decrease the production of MDA in lipid peroxidation.
In conclusion, vescalagin and gallic acid from pink wax apple fruit may decrease blood glucose level via their anti-inflammation and anti-oxidation stress abilities, therefore subsequently ameliorate the insulin resistance and carbohydrate metabolism in high fructose diet-induced prediabetic rats.

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