不同昇糖指數之根莖主食類對於高血糖及胰島素阻抗大白鼠其體內胰島素敏感性及胰島素訊息傳遞路徑之影響

本論文之目的有二：第一為測定臺灣幾種常見水果及根莖主食類的昇糖指數值 (glycemic index, GI)，第二個目的是以不同GI值的根莖主食類作為食材，並分別以高血糖及胰島素阻抗之大白鼠作為動物模式，探討不同GI值的根莖主食類對於大白鼠體內胰島素訊息傳遞路徑及胰島素敏感性之影響。第一部份：測定臺灣幾種常見水果及根莖主食類之GI值，實驗食材的水果類包括: 水梨、芭樂、香蕉、黃金奇異果、葡萄、荔枝、富士蘋果、木瓜、鳳梨、芒果及龍眼；根莖主食類則包括地瓜、馬鈴薯、玉米、蓮藕、芋頭及皇帝豆六種。結果顯示，水梨、蘋果、地瓜及蓮藕GI值較低；芋頭為中GI；龍眼、芒果、玉米及馬鈴薯GI值較高。從中挑選高GI的馬鈴薯及低GI的地瓜作為動物實驗的飼料介入食材。第二部份：本研究利用Sprague-Dawley (SD)鼠，以腹腔注射streptozotocin (STZ)/ nicotinamide以誘導大鼠產生高血糖，之後餵食含地瓜粉或馬鈴薯粉的飲食四週。在實驗前後各進行一次IPGTT (intraperitoneal glucose tolerance test) 實驗，四週後犧牲大鼠取其血液及骨骼肌進行胰島素訊息傳遞路徑相關蛋白質之分析。第三部份：先餵食SD大鼠高果糖飲食將之誘導成為胰島素阻抗的狀態，之後餵食含地瓜粉或馬鈴薯粉的飲食四週。四週後在胰島素的刺激下犧牲大鼠，取其血液及骨骼肌進行adipokines, 發炎性激素及胰島素訊息傳遞路徑相關蛋白質之分析。綜合以上兩部分研究結果顯示，在動物實驗中發現餵食含地瓜粉之飲食四週後，高血糖大鼠之血糖曲線下面積顯著下降，顯示其葡萄糖耐受性及餐後血糖反應已被改善。此外，餵食含地瓜粉之飲食的大鼠其骨骼中IRS-1及GLUT4之蛋白質表現量顯著上升。在胰島素阻抗的動物模式中，發現餵食含地瓜粉之飲食四週後，大鼠之血糖及胰島素曲線下面積、胰島素阻抗指標值 (HOMA-IR) 顯著下降，血液中發炎性指標 (包括TNF-α, resistin, RBP-4, IL-6) 的濃度也顯著下降。在胰島素的刺激下，發現餵食含地瓜粉之飲食的大鼠其骨骼中phospho-Tyr-IRS-1的表現量及細胞膜上GLUT4的表現量顯著上升。結論：餵食含地瓜粉之飲食四週後，可改善高血糖及胰島素阻抗大白鼠之餐後血糖反應及胰島素敏感性，並推測其機制可能與胰島素訊息傳遞路徑的正面調控及發炎現象的改善有關。

關鍵字

昇糖指數；胰島素敏感性；胰島素訊息傳遞；發炎

並列摘要

PURPOSES: This study was to measure the GIs of several kinds of fruits and starchy foods and evaluate the effects of low GI starchy foods on the insulin signaling and insulin sensitivity in the hyperglycemic and insulin-resistant rats. METHODS: This study was divided into three parts. Part 1 study: Measure the GIs of several common kinds of fruits and starchy foods in Taiwan, including pear, Fuji apple, papaya, guava, banana, pineapple, golden kiwifruit, grape, litchi, mango, longan, sweet potato, potato, corn, lotus root, taro and lima bean. Results showed that pear, apple, sweet potato and lotus root belong to low GI; taro belongs to median GI; longan, mango, corn and potato belong to high GI. We choose sweet potato and potato to be the sources of low- and high- GI starch. Part 2 study: Hyperglycemia was induced by using STZ/nicotinamide in Sprague-Dawley (SD) rats and then fed a diet containing 575 g/kg as either sweet potato starch or potato starch for 4 weeks. We did two IPGTTs before the start and 2 days before the end of the experimental period to observe the postprandial glycemic response. After 4 weeks, blood and the skeletal muscle was collected to measure the protein expression of insulin receptor (IR), insulin receptor substract-1 (IRS-1) and glucose transporter 4 (GLUT4). Part 3 study: SD rats were feed with high-fructose diet for 6 weeks to induce insulin resistance. Then the rats were fed with a diet containing 575 g/kg as either sweet potato starch or potato starch for 4 weeks. After 4 weeks, blood and the skeletal muscle was collected under the stimulation of insulin. Blood was used to measure the levels of adipocytokines and proinflammatory cytokines; the skeletal muscle was used to measure the protein expression of phosphorylayted-insulin receptor (IR), phosphorylayted-insulin receptor substract-1 (IRS-1) and glucose transporter 4 (GLUT4). RESULTS: From part 2 study, we found that the area under curve (AUC) for blood glucose at 4th week in the sweet potato starch-fed group were significant lower than those at 0th week. This result showed that compared to the potato starch-fed group, lower-GI sweet potato starch improved the postprandial glycemic response in hyperglycemic rats. The lower-GI sweet potato starch feeding for 4 weeks upregulated the protein expression of IRS-1 and GLUT4 in the skeletal muscle of hyperglycemic rats. From part 3 study, results showed that hyperinsulinemia and insulin sensitivity was improved in low-GI starch-fed rats. The concentration of TNF-alpha, IL-6, resistin and RBP-4 (retinol binding protein-4) were significantly lower in low-GI starch-fed rats. This suggested the proinflammatory status was improved in low-GI starch-fed rats. Low-GI starch feeding for 4 weeks significantly enhanced the protein expression of phospho-Tyr-IRS-1 and improved the translocation of GLUT4 to the plasma membrane in the skeletal muscle. CONCLUSION: Our results showed low-GI starch feeding for 4 weeks could improve the postprandial glycemic response and insulin sensitivity in hyperglycemic and insulin-resistant rats and may via the ameliorating of the adipocytokines, proinflammatory status and insulin signaling.