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  • 學位論文

七層塔在正常及糖尿病小鼠降血糖作用

Antihyperglycemic effect of Ocimum gratissimum L. in normal and diabetic mice

指導教授 : 紀宗呈

摘要


糖尿病為現今常見的代謝性疾病,如何有效預防與治療都為研究的主要方向,例如:能有效維持血糖的恆定,增加血液中葡萄糖的利用率,及改善胰島素敏感性。七層塔(Ocimum gratissimum L.)根據文獻指出具有抗發炎,保護肝等功效。 本論文研究在探討七層塔在動物實驗及細胞實驗中,改善糖尿病之作用機制。 研究中利用兩種誘導糖尿病小鼠的模式:(1)靜脈注射鏈脲佐菌素STZ 70 mg/kg,誘導第一型糖尿病小鼠;(2)高油高糖飲食誘導4週的第二型糖尿病小鼠;另外進一步去探討七層塔在C2C12肌母細胞中,所參與的醣類代謝機制。 結果表明七層塔在口服給予0.1 mg/kg、0.5 mg/ kg和1 mg/ kg劑量下,隨著劑量相關性的增加,具有改善高血糖的效果;而在空腹葡萄糖耐受性試驗(IPGTT)中,給予口服1 mg/kg,顯著增加葡萄糖的利用率;另外,口服七層塔1 mg/kg,對於糖尿病小鼠具有顯著增加肝醣的合成;在持續4週的治療下,七層塔能增加骨骼肌GLUT4蛋白的表現量。進一步研究也發現,在C2C12肌母細胞中,給予0.1 μg/ml、1μg/ml 和 10 μg/ml劑量下,隨著劑量相關性的增加,GLUT4蛋白具有顯著的表現量,另外在10 μg/ml劑量下AMPK顯著的增加表現量,而在AMPK抑制劑的存在下,確實阻斷掉了AMPK的表現。 本研究證實七層塔具有降血糖的作用,並且能增加糖尿病小鼠葡萄糖的利用率,以及肝醣合成能力,在C2C12細胞中活化AMPK,增加GLUT4蛋白的表現量,因此七層塔也許可做為具有改善糖尿病的天然藥草或新藥的開發。

並列摘要


Diabetes mellitus (DM) is a common metabolic disorder in nowadays. prevention and treatment, mainly include to maintain blood glucose levels and increase plasma glucose utilization rates, improvement insulin sensitivity. According to the reported Ocimum gratissimum L. (OG) has anti-inflammatory and protect the liver effect. We study aimed to investigate OG ameliorating effect of diabetes mellitus in vivo and vitro. Study induce diabetes models of type 1 and type 2 diabetes mice. The type 1 diabetes mice were intravenous injection of streptozotocin (STZ) 70 mg/kg and type 2 diabetes mice were feeding high-fat diet for 4 week. Further investigate in C2C12 cells OG was involved glucose uptake potential mechanisms . The study show that OG ameliorates hyperglycemia effect in dose-dependent 0.1 (mg/kg/p.o.) 0.5 (mg/ kg/p.o.) and 1 (mg/kg/p.o.) were significantly lowered the plasma glucose levels. However in intraperitoneal glucose tolerance test (IPGTT) with OG 1 (mg/kg) significantly increased glucose utilization rates. Further investigations in skeletal muscle of diabetes mice. OG 1 (mg/kg) significantly increased glycogen synthesis. In long-term treatment olar 1 (mg/kg/bid) for 4 week. OG increase skeletal muscle Glut4 expression. In C2C12 cells OG concentration-dependent 0.1 (μg/ml) 1 (μg/ml) and 10 (μg/ml) increased glut4 expression. Furthermore in C2C12 cells OG 1 (mg/kg) significant increase AMPK expression. This study proved OG in vitro increase skeletal muscle glucose uptake and glycogen synthesis. In vivo C2C12 cell activation of the AMPK pathway and GLUT4 expression. Therefore OG perhaps as a natural herb with improved diabetes Or the development of new drugs.

參考文獻


44. Chang, H.C., et al., Herbal supplement attenuation of cardiac fibrosis in rats with CCl(4)-induced liver cirrhosis. Chin J Physiol, 2014. 57(1): p. 41-7.
1. Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet, 2011, 378(9785):31–40.
2. WHO (2013) Diabetes Fact Sheet.
3. ZENG, Xiao-Yi, et al. Oleanolic Acid Reduces Hyperglycemia beyond Treatment Period with Akt/FoxO1-Induced Suppression of Hepatic Gluconeogenesis in Type-2 Diabetic Mice. PLoS One, 2012, 7.7: e42115.
4. Moller DE (2001) New drug targets for type 2 diabetes and the metabolic syndrome. Nature 414: 821–827.

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