肌少症 (Sarcopenia)是指肌肉質量下降與肌肉功能流失的一種疾病，為老年人口中相當普遍的疾病。肌少症患者的跌倒率、住院率，甚至是死亡率，都會比正常人高出許多。先前的研究發現患有第二型糖尿病 (Type 2 diabetes mellitus)的患者是肌少症的高風險族群，第二型糖尿病患者不僅具有較差的肌肉強度 (muscle strength)與肌肉質量 (muscle mass)，更具有較差的骨骼肌指數 (Skeletal muscle index)。因此為了探討肌少症與第二型糖尿病之間的關係，我們利用高脂飲食 (high fat diet)建立第二型糖尿病的動物模型。由此研究發現，與正常飼料組相比，第二型糖尿病動物不僅具有較差的骨骼肌指數，更具有較差的肌肉強度，而肌束的橫切面面積也較正常飼料組小。進一步利用RNA微陣列分析 (microarray)，我們發現在第二型糖尿病肌少症的動物中，myozenin-1 (MYOZ1)不僅具有較高的基因表現，也會與肌肉細胞的分化以及骨骼肌的葡萄糖代謝有關。而透過臨床試驗，我們分析出受試者血液中MYOZ1的表現量，與肌肉強度、骨骼肌指數以及糖化血色素之間的相關性。MYOZ1是主要存在於骨骼肌中的一種核蛋白 (nuclear protein)，主要參與調節鈣調節磷酸 (Calcineurin)的訊號傳遞，同時也會參與肌纖維 (myofibril)中Z線 (Z-line)的維持與第二型肌纖維的生長。而有研究發現過氧化體增殖活化受體-γ2 (Peroxisome proliferator-activated receptor-γ2, PPAR-γ2)基因上的啟動子 (promoter)具有MYOZ1的結合位置。PPAR-γ2對於調控骨骼肌的葡萄糖代謝 (glucose metabolism)與胰島素敏感性 (insulin sensitivity)是相當重要的。我們發現在糖尿病肌少症小鼠的骨骼肌中，MYOZ1具有較高的mRNA與蛋白表現量，並發現MYOZ1會促進L6肌肉纖維母細胞的分化，然而在L6細胞中，MYOZ1會促進PPAR-γ2與第四型葡萄糖轉運蛋白 (Glucose transporter 4, GLUT4)的表現，最後會增加L6細胞的葡萄糖攝取。此外，高糖 (High glucose)會增加MYOZ1在L6細胞中的表現量。但是在HFD小鼠的骨骼肌中，PPAR-γ2的表現是受到抑制的，而高脂肪酸會抑制PPAR-γ2的表現。總結以上我們認為MYOZ1不僅能促進骨骼肌的葡萄糖代謝，也能在第二型糖尿病肌少症中，扮演一個補償肌肉分化較差的角色。

MYOZ1, a nuclear protein, exclusively expressed in skeletal muscle which was involved in remodeling and growth of type-II fibers. It promotes the expression of peroxisome proliferator-activated receptor-γ2 (PPAR-γ2), and important for regulating glucose metabolism and insulin sensitivity of skeletal muscle. Sarcopenia is defined as a reduction of muscle mass and muscle strength. In addition to aging, type 2 diabetes is another important risk factor for sarcopenia. Type 2 diabetic patients were regularly accompanied with a serious loss of muscle mass and muscle strength. In order to investigate the relationship between type 2 diabetes and sarcopenia, we established high fat diet (HFD)-induced diabetes animal model to clarify this issue. Comparing with normal chow group, we found that HFD mice had a worse Skeletal muscle index and muscle strength. Moreover, we found that the expression of myozenin 1 (MYOZ1) was significantly increased in the muscle of HFD diabetic mice using microarray analysis. In clinical trials, we found that the correlation between the expression of MYOZ1 in blood and muscle strength, SMI and HbA1c. Overall, we speculated that MYOZ1 plays an important role in type 2 diabetic sarcopenia.

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