苦瓜蛋白調整血糖機制及其應用之研究(II)

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题名:	苦瓜蛋白調整血糖機制及其應用之研究(II)
其它题名:	Research and Application of Protein Components from Bitter Gourd on the Regulation of Glucose Metabolism (II)
作者:	項千芸;陳清助;侯庭鏞;吳世祿
贡献者:	中國醫藥大學微生物學科
日期:	2008-12
上传时间:	2010-09-05 15:22:19 (UTC+8)
摘要:	苦瓜已經用來作為糖尿病的替代療法，臨床試驗也已證實苦瓜可降低糖尿病病患的血糖值，然而，目前對於苦瓜的降血糖機制及其活性成分仍不清楚。本研究的主要目標是分析苦瓜種子水萃取液之組成份，並評估苦瓜種子萃取液在第二型糖尿病動物模式中的降血糖效應，進一步藉由DNA微陣列的分析方法探討苦瓜種子萃取液的降血糖機制。經由連續波長掃描及蛋白質體學分析，我們發現苦瓜種子萃取液中的組成以蛋白質為主，利用2D-LC/MS/MS進行功能性蛋白質成分之鑑定，發現inhibitor against trypsin 及napin-like protein large chain為主要組成份。動物試驗中發現口服苦瓜種子萃取液可明顯降低第二型糖尿病小鼠的血糖值，進一步我們選擇與葡萄糖代謝有關的組織，包括肌肉、脂肪組織、肝、腎，進行DNA微陣列分析，結果顯示表現最有差異的基因與胰島素訊息傳遞途徑相關，而且peroxisome proliferator activated receptor gamma (PPAR-γ) 在苦瓜種子萃取液降血糖的機制中扮演重要的角色。另外，我們利用免疫組織化學染色方法證實口服苦瓜種子萃取液的小鼠其肌肉、脂肪、肝、腎組織中 glucose transporter-4的表現明顯上升，此外苦瓜種子萃取液確實可明顯地活化細胞中PPAR-γ的活性。總結上述，我們的研究證實苦瓜種子萃取液可藉由調節PPAR-γ的活性，達到降血糖的效果。 Momordica charantia is used primarily as an alternative therapy for diabetes. Clinical trial has shown that M. charantia lowers blood glucose levels in patients with diabetes mellitus. However, the hypoglycemic mechanism and active constituents of M. charantia are still unclear so far. The aim of present study was to analyze the constituents in the aqueous extract of M. charantia seeds (MCSE), evaluate the hypoglycemic effect of MCSE in type 2 diabetic mice, and study the hypoglycemic mechanism of MCSE by oligonucleotide microarray approach. By sequential wavelength scanning and proteomic analysis, we found that the major components of MCSE were proteins and the major constituents were inhibitor against trypsin and napin-like protein large chain. Oral administration of MCSE significantly lowered the blood glucose levels in ob/ob mice. Microarray analysis of muscles, adipose tissues, liver, and kidney showed that most differentially expressed genes were connected with the insulin signaling pathway and that peroxisome proliferator activated receptor gamma (PPAR-) played a central role in the hypoglycemic mechanisms of MCSE. Furthermore, the expression of glucose transporter 4 was strongly increased in muscle, adipose tissue, liver, and kidney of the MCSE-treated mice. Moreover, MCSE significantly activated the PPAR- activity in cells. In conclusion, our study suggested that MCSE was a novel PPAR- modulator that exhibited the potent anti-diabetic effects.
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