第四型介白素在第二型糖尿病之致病角色

Role of Interleukin-4 in the Pathogenesis of Type 2 Diabetes Mellitus

盧思宏(Si-Hong Lu)

指導教授 ： 張懿欣

中山醫學大學/醫學院/免疫學研究所/碩士(2008年)

https://doi.org/10.6834/CSMU.2008.00030

摘要

糖尿病依照病因及病理學上的不同主要可區分為第一型與第二型兩種，各自有著獨特的病因及臨床表現。第二型糖尿病患者在臨床上會表現高血糖以及較低的胰島素分泌量。近來有文獻指出在第二型糖尿病患者體內有慢性發炎反應，患者血漿中會含有較多由第一型介白素(interleukin-1, IL-1)、第六型介白素(interleukin-6, IL-6)與甲型腫瘤壞死因子(tumor necrosis factor-α, TNF-α)等細胞激素作用而產生的急性發炎反應相關物質。因此，第二型糖尿病被認為是一種慢性發炎疾病，許多調控TH1 以及TH2淋巴球免疫反應的細胞激素在血液中濃度會受到影響。本實驗室先前研究中發現，利用低劑量STZ誘導第四型介白素(interleukin-4, IL-4)分泌量較高的BALB/c小鼠，糖尿病發病的速度會比IL-4分泌量較低的C57BL/6小鼠較快，症狀表現也較明顯。為了進一步證實IL-4與第二型糖尿病的關係，我們使用高脂肪餵食以及低劑量STZ誘導IL-4分泌量較高的BALB/c小鼠產生第二型糖尿病，並在過程中利用IL-4單株抗體中和IL-4作用，以觀察IL-4與第二型糖尿病發病的關係。結果發現，在所有誘發為第二型糖尿病的BALB/c小鼠之葡萄糖耐受性試驗過程中，在第120分鐘時可持續觀察到高血糖現象，而其中使用IL-4單株抗體降低體內IL-4濃度的小鼠之葡萄糖耐受性試驗的血糖濃度則明顯較高。因此，在誘導BALB/c小鼠產生第二型糖尿病的過程中降低體內IL-4濃度，會使得葡萄糖的耐受性更差，並且加重第二型糖尿病的症狀與病程，顯示IL-4在第二型糖尿病中似乎扮演著保護的角色。

關鍵字

第二型糖尿病 ； 第四型介白素 ； 高脂肪餵食 ； 酵素免疫分析

並列摘要

Diabetes mellitus (DM) is mainly classified into type 1 and type 2 diabetes (T2DM) based on its etiology and pathophysiology, with respective unique clinical and etiological features. T2DM is characterized by abnormally high blood glucose resulting from a relative deficiency of insulin. Recent finding suggested T2DM is an inflammatory condition characterized by elevated concentrations of acute phase inflammatory reactants in the plasma, which are stimulated by cytokines, mainly interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Consequently, T2DM is a chronic-phase disease and can influence many TH1 and TH2 cytokines. Our preliminary study demonstrated that under STZ induction, BALB/c mice with higher IL-4 secreting ability developed diabetes more rapidly and prominently than low IL-4 secreting C57BL/6 mice. In this context, this study investigated the correlation between IL-4 and T2DM by observing the T2DM onset and development in antibody neutralization test in high fat diet (HFD) feeding and streptozotocin (STZ) inducing T2DM male BALB/c mice. In the glucose tolerance test, the blood glucose concentration in the IL-4 antibody treated mice was significantly higher. The glucose tolerance and the progression of T2DM were deteriorated, by decreasing the IL-4 concentration during T2DM induction in BALB/c mice. The above results suggested that IL-4 may played a protective role in T2DM.

並列關鍵字

type 2 diabetes mellitus ； IL-4 ； high fat diet ； ELISA

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