抗壞血酸處理及胰島素刺激在脂肪細胞中降低高葡萄糖引誘之活性氧產量及粒線體失能

Ascorbic acid treatment and insulin stimulation reduced high glucose-induced ROS production and mitochondrial dysfunction in adipocytes

黃晴瑜(Ching-Yu Huang)

指導教授 ： 徐瑞洲 ； 李宜靜

國立清華大學/生命科學院/分子醫學研究所/碩士(2013年)

摘要

胰島素阻抗為第二型糖尿病之病理特徵，且伴隨著許多發病因子，如增加氧化壓力及粒線體失能。部分文獻證實出活性氧產生的壓力以及粒線體功能缺失皆參與發病過程，但其分子機制仍然不明。Glucose transporter 10，簡稱GLUT10，屬於第三類型葡萄糖運送家族，並且是由位於染色體上與糖尿病有關之20q12-13.1區域中的SLC2A10基因轉譯。 先前我們實驗室已證實在GLUT10大量表達的脂肪細胞中可藉由胰島素刺激移動至粒線體，此外，GLUT10為脫氫抗壞血酸運送子的功能可保護細胞免於由雙氧水產生之氧化壓力的傷害。在此篇研究中，我們想更加了解GLUT10和糖尿病的關係。我們使用高葡萄糖處理脂肪細胞模擬高血糖狀態。此處理不僅導致活性氧壓力增加、還會降低粒線體膜電位和耗氧量。另外，我們發現在這些脂肪細胞補充抗壞血酸不只可以降低活性氧的產生、還能增加粒線體膜功能，這些情況在加入胰島素刺激後有更大的改善。我的結果提供一個研究GLUT10和第二類型糖尿病關係的高葡萄糖壓力條件。

關鍵字

脂肪細胞

並列摘要

Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is accompanied many pathological factors, such as increased oxidative stress and mitochondrial dysfunction. Some studies evidenced that reactive oxygen species (ROS) and mitochondrial dysfunction are involving in the pathological progress, but the molecular mechanisms are still unclear. Glucose transporter 10 (GLUT10) is a member of class III glucose transporter family and encoded by SLC2A10 gene which is located on chromosome 20q12-13.1 where was an association with type 2 diabetes. Previously, our lab has reported that GLUT10 transfers to mitochondrial under insulin stimulation in adipocytes where the GLUT10 is largely expressed. In addition, GLUT10 transports L-dehydroascorbic acid (DHA) in to mitochondria and against oxidative stress under H202-induced stress condition.
In this study, we aim to understand the association between GLUT10 and T2DM. We mimic hyperglycemic condition using high glucose treating adipocytes. The treatment leads to increase ROS stress, collapse mitochondrial membrane potential, and decrease oxygen consumption rate. In addition, we found that replenishment with ascorbic acid can not only reduce the intracellular ROS production, but also increase mitochondrial function in adipocytes. Furthermore, treated these adipocytes with insulin can further improve ROS stress and mitochondrial function. My results provide a high glucose stress condition to study the correlation between GLUT10 and insulin resistance in adipocytes.

並列關鍵字

adipocytes

參考文獻

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