糖尿病常因胰島素的作用異常所致血糖偏高的一種新陳代謝疾病，其中，第二型糖尿病又佔了糖尿病患者的90%以上。胰島素抗阻性(insulin resistance)則是形成第二型糖尿病的原因之一，因此，藉由改善胰島素抗阻性來改善第二型糖尿病是當今重要的方向。
　　Agmatine是arginine去羧基化後的反應產物，在體內被認為是一種神經傳導物質，可和Imidazoline受體結合而產生作用。以靜脈注射Agmatine到第一型糖尿病老鼠，曾觀察到降血糖的作用；此作用是藉由活化腎上腺的I2-imidazoline受體，造成β-endorphin釋放來活化μ receptor所得到。於是，本研究想繼續探討Agmatine對胰島素抗阻性的效果，並探討其可能的機轉。
　　本項實驗使用胰島素抗阻的動物，包括：果糖誘發的胰島素抗阻性老鼠或遺傳型的肥胖老鼠(obese Zucker rat)，來進行研究。另外，使用灌流(Hyperinsulinemic euglycemic clamp)、葡萄糖耐受性試驗(Glucose tolerance test)、HOMA-IR (Homeostasis model assessment-insulin resistance) 及藥物測試(Tolbutamide test)等方法來探討Agmatine對胰島素抗阻性的改善效果。
　　首先，使用臨床常用的HOMA-IR來評估胰島素抗阻的實驗，乃將遺傳型的肥胖老鼠(obese Zucker rat)經由靜脈給與Agmatine (1mg/kg)每天三次，連續14天；分別在第零、七、十四天抽血，測其禁食狀態的血糖值(mmol/l)及胰島素濃度(μU/ml) ，再將這兩個值相乘之後，除以22.5即可得HOMA-IR指數。結果發現，在第十四天的HOMA-IR指數(8.43±1.64)比第零天(19.31±2.24)更低，且有顯著的差異(p﹤0.05)；表示Agmatine可以改善基因突變老鼠的胰島素抗阻。
　　另外，將果糖誘發胰島素抗阻性的老鼠分成四組，分別是(1) Control組(2) Agmatine (1mg/kg)組(3) Naloxonazine (2mg/kg)加上Agmatine(1mg/kg)組(4) BU224 (1mg/kg)加上Agmatine (1mg/kg)組，它們皆接受腹腔注射葡萄糖耐受性的實驗；以注射葡萄糖的時間為零點，分別於30、60、90、120分鐘抽血。結果，Agmatine (1mg/kg)組的血糖值比Control組來得低，且有顯著差異(p﹤0.05)。然而，這個作用可被Naloxonazine (2mg/kg)及BU224 (1mg/kg)所阻斷，其血糖值會恢復到接近Control組。接著，由Enzyme-linked immunosorbent assay (ELISA)得知，Agmatine會以劑量相關性增加果糖大白鼠及基因突變老鼠血中的β-endorphin含量，且將果糖大白鼠兩側的腎上腺摘除後，發現給與Agmatine最大劑量(3mg/kg)卻無法增加其血中的β-endorphin含量。因此，Agmatine具有改善胰島素抗阻性的作用，其作用機轉可能是藉由活化腎上腺I2-imidazoline受體後，促進分泌更多的β-endorphin來活化嗎啡μ型受體所產生的。除此之外，由果糖SHR老鼠實驗結果得到Agmatine會以劑量相關性去改善高血壓。因此，Agmatine不但可以改善胰島素抗阻性，同時也可改善高血壓。

　　Diabetes mellitus (DM) is a metabolic disease caused by impaired insulin action, and 90% diabetic patients belong to type Π diabetes. Because insulin resistance is a major of type Π diabetes, it is the main target to treat type Π diabetes by improving insulin resistance.
　　Agmatine is the decarboxylation product of amino acid arginine, and it is regarded as a kind of neurotransmitter exerting its effects by binding to imidazoline receptors in vivo. Previous studies showed that agmatine can lower plasma glucose in type Ι diabetic rats by intravenous injection. Also, the glucose-lowering action of agmatine is due to an activation of imidazoline receptors in adrenal gland which leads to the release of β-endorphin to activate opioid receptors. Therefore, the present study was designed to investigate the effect of agmatine on insulin resistance and discuss its possible mechanism.
　　In this experiment, we used animals expressing insulin resistance, including fructose-fed rats and genetically obese Zucker rats. In addition, we investigated the effect of agmatine on insulin resistance by using the methods of hyperinsulinemic euglycemic clamp、glucose tolerance test、HOMA-IR (Homeostasis model assessment- insulin resistance)、and tolbutamide test.
　　At first, we use the clinical HOMA-IR to evaluate insulin resistance. Then, we treated obese Zucker rats with agmatine 1mg/kg three times a day for 14 days by continuous intravenous injections, and drew blood to measure the fasting plasma glucose (mmol/l) and plasma insulin (μU/ml) on the 0th、7th、14th day, respectively. Then, we obtained HOMA-IR index from the two parameters in a formula. As a result, we found that the HOMA-IR index on the 14th day is lower than that on the 0th day, and it showed obvious difference between them (P<0.05). The data indicate that agmatine can improve insulin resistance in genetically obese Zucker rats from homeostasis model assessment-insulin resistance (HOMA-IR).
　　Moreover, in the experiment of glucose tolerance test, we divided fructose-fed rats into 4 groups: (1) control group (2) agmatine (1mg/kg) group (3) naloxonazine (2mg/kg)+agmatine (1mg/kg) group (4) BU224 (1mg/kg) +agmatine (1mg/kg) group. We found that plasma glucose and insulin in the agmatine group were lower than those in the control group, and it showed obvious difference between them (P<0.05). However, the action of agmatine in fructose-fed rats in the intraperitoneal glucose tolerance test could be reversed by intravenous injection of naloxonazine (2mg/kg) and BU224 (1mg/kg). In addition, we found that agmatine increased plasma β-endorphin in fructose-fed rats and obese Zucker rats in a dose-dependent manner, but not in adrenalectomised rats. In conclusion, the obtained results indicate that agmatine plays an important role in improving insulin resistance, and this mechanism is mediated by activating I2-imidazoline receptors in adrenal gland, stimulating the release of more β-endorphin to activate opioid μ-receptors. In addition, agmatine can lower blood pressure of fructose-fed SHR rats in a dose-dependent manner. Therefore, this means that agmatine improves not only insulin resistance but also hypertension.

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