Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/52129
標題: EGCG對糖尿病患者sRAGE釋放之調控作用
Regulatory effect of EGCG on sRAGE secretion in diabetes patients
作者: 黃祥閔
Huang, Shang-Ming
關鍵字: 第2型糖尿病
EGCG
綠茶萃取物
剪切作用
ADAM10
EGCG
RAGE
S100A12
sRAGE
RAGE
sRAGE
diabetes
S100A12
ADAM10
出版社: 食品暨應用生物科技學系所
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摘要: RAGE (receptor for advanced glycation of end products)在第2型糖尿病之病理進展過程中扮演重要之角色。sRAGE (soluble form of RAGE)為RAGE之異構物,同時可以與RAGE競爭其配體 (RAGE ligand),因此對於抑制ligand-RAGE交互作用以預防第2型糖尿病病變具正面之角色。本研究目的為探討富含EGCG (epigallocatechin-3-gallate)之綠茶萃取物(Green tea extract, GTE; 300-900 mg/day)對第2型糖尿病病患血漿中sRAGE與S100A12 (RAGE ligand)含量之影響;同時探討EGCG調控sRAGE釋放之可能機轉。本試驗以光田綜合醫院新陳代謝科門診病患為研究對象,收集符合第2型糖尿病患者51人,並通過該醫院人體試驗委員會之同意後進行試驗。試驗結果顯示,EGCG可以有效促進第2型糖尿病人血漿中sRAGE之含量,同時可以有效抑制血漿中S100A12 RAGE ligand之含量。此外,EGCG促進sRAGE之釋放機轉是透過刺激ADAM10對胞外RAGE之剪切作用。本論文研究成果發現,糖尿病患者補充EGCG可以有效調控ADAM10對RAGE之剪切作用以促進sRAGE釋放並抑制S100A12-RAGE之交互作用。因此,EGCG幫助糖尿病患者控制病情,不僅來自於EGCG本身強大之抗氧化特性,同時亦是因其具有調控sRAGE釋放以抑制S100A12-RAGE之能力。此外,ADAM10剪切RAGE以促進sRAGE釋放應為未來具潛力抑制糖尿病人體內RAGE活化之重要機轉。
The receptor for advanced glycation of end products (RAGE) plays a critical role in the progression of Type 2 diabetes (T2D). Soluble RAGE (sRAGE) is one of RAGE variants, which acts as a decoy domain receptor and competes with RAGE, thus contributing to prevention of T2D. In this study, we conducted clinical trials of EGCG-rich green tea extract (300-900 mg/day) to investigate the effect of EGCG on relationship between S100A12 RAGE ligand and diverse sRAGE in T2D. Moreover, mechanism of sRAGE production also confirmed in vitro. Our data indicated that EGCG could stimulate sRAGE circulation but inhibited RAGE ligand in T2D, and ADAM10-mediated ectodomain shedding of extracellular RAGE was mainly involved in EGCG-stimulated sRAGE circulation. The present evidence indicates that EGCG has potential to block S100A12-RAGE axis by stimulating sRAGE production through ADAM10-mediated ectodomain shedding of extracellular RAGE. Therefore, EGCG contributes to nutritional strategies for diabetes, not only because of its efficient antioxidant activity to scavenge free radicals, but also because of its ability stimulating sRAGE release in the circulation. Additionally, ADAM10-induced ectodomain shedding of extracellular RAGE leading to sRAGE circulation should be a potential of passive mechanism of sRAGE production to block S100A12-RAGE axis-related pathogenesis of pro-inflammation and diabetes.
URI: http://hdl.handle.net/11455/52129
其他識別: U0005-0208201315592700
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