胰島素與過氧化氫對人類神經瘤母細胞葡萄糖攝入訊息路徑的影響

Effects of insulin and hydrogen peroxide on glucose uptake signaling in human neuroblastoma cells

陳曼文(Man-Wen Chen)

指導教授 ： 林士祥

臺北醫學大學/公共衛生暨營養學院/保健營養學研究所/碩士(2011年)

摘要

全世界許多國家已邁入老年化社會，神經退化性疾病的盛行率也日漸上升，其中阿茲海默症 (Alzheimer’s disease, AD) 是最普遍的一種。由於AD的病程漫長且受到許多因子的影響，延緩病程的發展是首要目標。流行病學研究指出糖尿病病患出現認知異常的頻率較高且罹患AD的相對危險率增加30-65%，其中胰島素抗性與氧化壓力可能扮演重要角色。氧化壓力會干擾胰島素訊息傳遞進而使AD的病理蛋白質生成量增加，同時會對神經細胞造成氧化傷害並誘發凋亡反應。目前許多研究探討治療糖尿病能否延緩AD的病徵，需要利用胰島素抗性的神經細胞作為實驗模式。過去有文獻利用膽固醇或神經醯胺誘發神經細胞之胰島素抗性，然並非以氧化壓力的角度切入。本實驗以人類神經瘤母細胞株SHSY5Y作為模式，並利用氧化壓力誘發其胰島素抗性。結果發現H2O2介入下會降低未分化SHSY5Y細胞中胰島素誘發之葡萄糖類似物攝入量，且會降低分化SHSY5Y細胞磷酸化Akt/總Akt比值。顯示H2O2可能會干擾人類神經瘤母細胞的胰島素反應，然而仍需進一步的實驗以建立此模式。

關鍵字

氧化壓力 ； 人類神經瘤母細胞 ； 葡萄糖攝入

並列摘要

Alzheimer’s disease (AD) is the most common neurodegeneration disease and dementia. There are many factors involved in the progression of AD, including aging, type 2diabetes mellitus (T2DM) and oxidative stress. Epidemiologic studies have indicated an increased relative risk for dementia in T2DM patients, and insulin resistance and oxidative stress might affect the underlying mechanisms. In order to investigate the relationship within oxidative stress, insulin resistance and AD, we aimed to establish the model for oxidative stress-induced insulin resistance in neuron cell. The results showed that H2O2 treatment might reduce insulin-induced glucose analog uptake in undifferentiated SHSY5Y cells and inhibit pAkt/Akt ratio in differentiated SHSY5Y cells, which indicated H2O2 could attenuate the insulin effect in human neuroblastoma cell. However, further experiments should be done for establishing the model.

並列關鍵字

oxidative stress ； human neuroblastoma cell ； glucose uptake

參考文獻

2. Hardy J, D. A: Amyloid deposition as the central event in the aetiology of Alzheimer's disease Trends Pharmacol Sci 1991, 12:383-388.

3. Swerdlow R: Mitochondria in cybrids containing mtDNA from persons with mitochondriopathies. J Neurosci Res 2007, 85:3416-3428.

4. Wolfe M: When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/ Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Rep 2007, 8: 136-140.

5. Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, DeTure M, Ramsden M, McGowan E et al: Tau suppression in a neurodegenerative mouse model improves memory function. Science 2005, 309(5733):476-481.

6. Oddo S, Vasilevko V, Caccamo A, Kitazawa M, Cribbs DH, LaFerla FM: Reduction of soluble Abeta and tau, but not soluble Abeta alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. J Biol Chem 2006, 281(51):39413-39423.