第四型介白素於肌肉分化及葡萄糖運送中扮演之角色

Role of Interleukin-4 in myogenesis and Glucose transport.

鄭欣怡(Hsin-Yi Cheng)

指導教授 ： 張懿欣

中山醫學大學/醫學科技學院/醫學檢驗暨生物技術學系碩士班/碩士(2010年)

https://doi.org/10.6834/CSMU.2010.00061

摘要

糖尿病為常見的代謝性疾病，主要特徵為高血糖。一般依其病因及病理學可區分為第一型糖尿病及第二型糖尿病。已知第二型糖尿病為一種慢性發炎性的疾病，病患血漿中interleukin-1 (IL-1)、interleukin-6 (IL-6)及tumour necrosis factor-α (TNF-α)等Th2細胞所分泌的發炎激素表現量會增加。本實驗室先前的研究中發現第二型糖尿病病患體內IL-4分泌量較高，且患者與健康個體之IL-4基因啟動子多型性(promoter gene polymorphism)也有顯著差異。動物實驗發現，IL-4分泌量較高的老鼠經由單次注射低劑量STZ誘發第二型糖尿病的病程進展較快速且症狀較為嚴重。基於上述結果，本實驗之目標為利用老鼠的肌纖維母細胞C2C12為實驗模式，進一步探討IL-4對胰島素目標細胞之肌肉細胞的影響，同時探究IL-4在第二型糖尿病中所扮演的角色。實驗結果發現IL-4會促進肌纖維母細胞分化為成熟肌細胞的肌肉分化過程(myogenesis)；包括myosin heavy chain (MyHC)、myogenin、muscle-restricted coiled-coil protein (MURC)等肌細胞分化標記蛋白(marker)的表現量都會上升。此外，IL-4可促進成熟肌細胞的胰島素訊息傳遞，其主要訊息傳遞之蛋白Akt磷酸化有上升的情形，而成熟肌細胞的培養環境中同時加入IL-4及胰島素時，肌細胞攝取葡萄糖能力與葡萄糖轉運蛋白(glucose transporter 4 [GLUT-4])轉移(translocation)到細胞膜的蛋白表現量都會增加。由上述實驗結果可以推測，IL-4可以調控肌肉細胞的分化，並且也可與胰島素一起調控成熟肌肉細胞的葡萄糖攝取能力。

關鍵字

第四型介白素 ； 肌肉分化 ； 葡萄糖運送

並列摘要

Diabetes mellitus (DM) is a common metabolic disease with hyperglycemia as the major characteristics. According to the etiology and pathgenesis, DM can be classified as type 1 and type 2 diabetes (T2DM). Evidence has indicated that T2DM is a chronic inflammatory condition. Circulatory Th2 cytokines levels in patients with T2DM are elevated, such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). Our previous study demonstrated that individuals with genotypes of higher interleukin-4 (IL-4)-secreting ability were more susceptible to diabetic development. In this context, the present study aimed at investigating the possible role and regulation of IL-4 to the metabolism of muscle cells using murine myoblast C2C12 as an experimental model. Our results showed that the expression levels of myogenic makers, including myocin heavy chain (MyHC) and myogenin, were upregulated in the presence of IL-4 treatment. Levels of phosphorylated Akt, a major mediator of insulin signaling pathway, was up-regulated in mature myocyte by IL-4 treatment. The glucose uptake ability and glucose transpotor-4 (GLUT-4) translocation were enhanced under IL-4 and insulin treatment. The above results suggested that IL-4 may promote myogenesis and up-regulate glucose uptake in the presence of insulin.

並列關鍵字

interleukin-4 ； myogenesis ； glucose transport

參考文獻

American Diabetes Association. http://www.diabetes.org/index.jsp

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