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標題: 胰島素對基因缺陷及高脂飼料餵食小鼠Akt活性之影響
Effects of Insulin on Akt Activities in Gene Deficient and High-Fat Diet Fed Mice
作者: 邱宜昕
Chiu, Yi-Shin
關鍵字: Akt
insulin resistance
high-fat diet
gene deficient
出版社: 獸醫學系暨研究所
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摘要: Akt是胰島素訊息路徑中的重要一環,位於PI 3-kinase下游,直接影響標的器官的葡萄糖運輸,缺乏Akt或Akt活性降低的臨床表現為胰島素阻抗,一旦出現胰島素阻抗,將有引發第二型糖尿病及心血管疾病等代謝症候群的高度危險性,而肥胖與胰島素阻抗又息息相關,其中以遺傳因子及飲食所導致的肥胖最為重要。本研究利用C57BL/6JNarl mice,餵飼一般飼料及高脂飼料六週,在給予一針胰島素(2 IU/kg)後犧牲,探討飲食造成的肥胖與胰島素阻抗之間的關聯性。結果顯示,經高脂飲食誘導之C57BL/6JNarl小鼠,禁食體重及血糖與一般飼料組沒有明顯差異,但高脂飼料組具有葡萄糖耐受性不良及胰島素敏感性不良之情形,且犧牲後高脂飲食組副睪脂肪總重顯著高於一般飼料組 ( P < 0.05);而在胰島素刺激後ㄧ小時的胰島素訊息路徑中, Akt總量及Akt磷酸化Thr308在肝臟、肌肉皆與一般飼料組沒有差異,然而在脂肪,不論是Akt總量或磷酸化Thr308,高脂飲食組皆顯著高於一般飼料組,故推測高脂飲食誘導肥胖初期,胰島素阻抗情形不嚴重,並且在脂肪會代償性的增加Akt總量及磷酸化Thr308的活性,以利胰島素訊息傳遞的進行;本研究亦利用B6.V-Lepob/J及BKS.Cg-+ Leprdb /+ Leprdb/J小鼠,餵飼ㄧ般飼料,探討遺傳因子與胰島素阻抗的關連性,結果顯示兩者禁食體重及血糖皆顯著高於C57BL/6JNarl小鼠 ( P < 0.001 );在胰島素刺激後ㄧ小時的胰島素訊息路徑中,兩者在肝臟、肌肉及脂肪的Akt總量表現不一致,而Akt磷酸化Thr308表現量在肝臟、肌肉及脂肪皆顯著低於C57BL/6JNarl小鼠(P < 0.05),顯示B6.V-Lepob/J及BKS.Cg-+ Leprdb /+ Leprdb/J小鼠在主要代謝器官中胰島素刺激之Akt訊息低下,與高脂飲食誘導C57BL/6JNarl小鼠胰島素阻抗初期的訊息表現不盡相同。因此,選擇適當的代謝症候群動物模式,有助於肥胖及第二型糖尿病機制之深入研究。
Insulin resistance is a common factor in type 2 diabetes, obesity and cardiovascular disease, which results from genetic background and/or environmental factors (especially diet). Akt stands as the furthest known downstream component of the insulin-signaling pathway that direct leads to glucose transport. In this study, C57BL/6JNarl (B6) mice were fed with high fat diet for 6 weeks. Mice were sacrificed an hour after acute insulin (2 IU/kg) administration. Mice fed with high fat diet showed impaired glucose tolerance. However, the levels of Akt and Akt-phosphorylated Thr308 in epididymis adipose tissue increased significantly. These results indicated that the expression of Akt increased in adipose tissue may act to compensate insulin resistance. Insulin signaling of B6.V-Lepob/J (ob/ob) and BKS.Cg-+ Leprdb /+ Leprdb/J (db/db) mice fed with normal diet were also examined. The fasting body weight and blood glucose in ob/ob and db/db mice were significantly higher than B6 mice. After insulin stimulation, the levels of Akt-phosphorylated Thr308 in liver, muscle and adipose tissue were significantly decreased compared with B6 mice. These results indicated that the pattern of Akt expression and activation in ob/ob and db/db mice are different from high-fat diet fed B6 mice. Therefore, it is important to select an appropriate animal model to study insulin resistance and metabolic syndrome.
其他識別: U0005-1707200715572200
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