摘要
糖尿病的原因通常可被分成兩類：第一類主要是「第一型糖尿病」由於胰島素無法順利分泌所致；第二類主要是「第二型糖尿病」與胰島素分泌無關，主要由於身體對胰島素敏感度下降所致，過去曾稱為「成年型糖尿病」，但亦可發生於年輕人。此類型雖有部分病人胰島素的分泌減少，但大多數患者分泌胰島素的能力尚可。此外，本類型的病人大多會伴隨胰島素抗阻性（insulin resistance）的出現。胰島素抗阻性的形成主要是因胰臟蘭氏小島的β細胞過度地分泌胰島素（hyperinsulinemia），造成骨骼肌、脂肪組織及肝臟等周邊組織對胰島素的敏感性（insulin sensitivity）降低。因此，減低了組織對葡萄糖的利用率，而造成高血糖的現象。 有文獻指出，刺五加具降血糖作用，欲進一步了解刺五加的降血糖機轉與是否具有胰島素抗性改善作用，故使用刺五加主要成分之一:紫丁香?(Syringin)進行實驗。 為了有效地評估紫丁香?是否可直接改善胰島素抗性，於是利用紫丁香?在葡萄糖耐受性試驗 (Glucose tolerance test) 對glucose-insulin index的影響，發現在果糖誘發的胰島素抗性大白鼠身上，紫丁香?會以劑量相關性降低血糖及血中胰島素的含量。另外，在 glucose-insulin index，隨著紫丁香?劑量的增加，該指標也會隨之遞減。由此可知，紫丁香?對果糖誘發的胰島素抗性大白鼠具有改善作用。 紫丁香?原本降低的glucose-insulin index會因嗎啡?型受體阻斷劑Naloxone的投予所解消。表示嗎啡?型受體的活化可以緩解胰島素抗性的現象。為了研究活化?型受體來改善胰島素抗性可能的作用機轉。於是，進一步確認胰島素訊息路徑的改變。由西方點墨分析法，發現紫丁香?可提高果糖大白鼠骨骼肌之IRS-1 (Tyr)，PI-3 kinase (p85?)，Akt (Ser473) 磷酸化的表現量。 選擇小鼠骨骼肌細胞株 (mouse myoblast cell line) 的C2C12肌母細胞來進行葡萄糖吸回的實驗 結果發現，隨著紫丁香?濃度的遞增，C2C12肌母細胞對葡萄糖的吸入作用也隨之增強，呈現劑量相關性。以嗎啡?型受體阻斷劑(naloxone或是naloxonazine)前處理C2C12 ，可完全解消紫丁香?刺激C2C12肌母細胞的作用。 紫丁香?在TNF-?引致的胰島素抗性C2C12肌母細胞對葡萄糖吸入作用之影響，紫丁香?對TNF-?引致的胰島素抗性也有改善的效果。以嗎啡?型受體阻斷劑(naloxone或是naloxonazine)前處理TNF-?處理C2C12肌母細胞，可完全解消紫丁香?刺激TNF-? 引致的胰島素抗性C2C12細胞的作用。 紫丁香?在胰島素抗性的C2C12肌母細胞對胰島素訊息路徑及葡萄糖轉運蛋白 GLUT4 的影響，發現紫丁香?可提高胰島素抗性的C2C12肌母細胞之IRS-1 (Tyr)，PI-3 kinase (p85?)，Akt (Ser473) 磷酸化的表現量；同時，也增強下游GLUT4蛋白的表現量。 綜合以上的結果，無論在體內或體外的試驗，紫丁香?皆可使胰島素抗性獲得有效地緩解。
並列摘要
There are two types of diabetes mellitus(DM): Type 1 DM is IDDM( insulin dependent DM) that is due to failure of insulin secretion of the pancreatic β-cell. Type 2 DM is NIDDM( non-insulin dependent DM) that can be characterized by a diminished ability of insulin sensitivity. Type II DM is so-called adult-type DM because the disease usually develops in the patients elder than 40 years old, but it can develop in the young persons. The ability of insulin secretion is normal in most Type 2 DM patients ; besides, it always accompanies with insulin resistance. The key feature of insulin resistance is oversecretion of pancreatic β-cell, leading to hyperinsulinemia that can diminish insulin sensitivity in target tissues, such as skeletal muscle, fatty tissue and liver. Therefore, it shows a significant decrease of glucose uptake and leads to hyperglycemia. Eleutherococcus senticosus that has the physiologic effect of treating hyperglycemia has been reported in the literature.In order to understand the mechanisms of treating hyperglycemia of Eleutherococcus senticosus and it’s effect of treating insulin resistance, we use one of the major component of Eleutherococcus senticosus “ Syringin” to carry out our experiments. Syringin was obtained for glucose tolerance tests and evaluated the effects of glucose-insulin index.In fructose-induced insulin resistance rats, we found that syringin can lower the plasma glucose and insulin level in the association of dose dependence. Besides, the higher concentrations of the syringin was added , the lower glucose-insulin index was obtained. Therefore, we can concluded that syringin has the physiologic effect to treat insulin resistance in fructose-induced insulin resistance rats. The lowered glucose-insulin index will be blocked when we give naloxone (antagonist of opioid β-receptor). The results presented that activation of opioid β-receptor can diminish the effect of insulin resistance. In order to realize the possible mechanisms, Western blotting was employed to detect the amounts of IRS-1( Tyr ), PI-3 kinase( p85α ), and Akt( Ser473 ) phosphorylation to nuderstand the insulin signal pathways.The results showed that syringin can elevate the protein expression of IRS-1( Tyr ), PI-3 kinase( p85α ), and Akt( Ser473 ) phosphorylation in fructose-induced insulin resistance rats. We selected mouse myoblast cell line C2C12 to undergo the test of glucose uptake.We found that the more concentration of Syringin was added, the stronger effect of glucose uptake of the C2C12 cell line was obtained. However, the effect disappeared when we pretreated the C2C12 cell line with naloxone or naloxonazine. When we added syringin in TNF-α induced insulin resistance C2C12 cell line, glucose uptake level increased markedly. However, the effect disappeared when we pretreat the C2C12 cell line with naloxone or naloxonazine. Syringin can elevate the protein expression of IRS-1( Tyr ), PI-3 kinase( p85α ), and Akt( Ser473 ) phosphorylation in insulin resistant C2C12 cell. Besides, syringin can increase protein expression of GLUT4. Thus, the present study found that syringin can improve insulin resistance both in vivo or in vitro.
參考文獻
延伸閱讀
- 牛河山（2010）。紫丁香苷的降血糖作用之研究〔博士論文，臺北醫學大學〕。華藝線上圖書館。https://doi.org/10.6831/TMU.2010.00228
- 劉咸君（2006）。綠茶表沒食子酸酯型唲茶素酸酯對胰島素刺激前脂肪細胞增生的抑制〔碩士論文，國立中央大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0031-0207200917335186
- 張巧俐（2011）。粉紅種蓮霧幼果水萃物減輕以腫瘤壞死因子 (TNF-α) 處理之小鼠肝臟細胞 (FL83B) 胰島素阻抗及改善醣類代謝之研究〔碩士論文，國立臺灣大學〕。華藝線上圖書館。https://doi.org/10.6342/NTU.2011.02843
- 吳昀軒（2016）。檜木醇抑制3T3-L1脂肪細胞分化及增加胰島素在脂肪細胞的功效〔碩士論文，中山醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0003-2107201613521100
- Muscogiuri, G., Palomba, S., Laganà, A. S., & Orio, F. (2016). Inositols in the Treatment of Insulin-Mediated Diseases. International Journal of Endocrinology, 2016(), 366-381-041. https://doi.org/10.1155/2016/3058393