Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/13984
標題: Rosiglitazone對glucosamine去敏感化大白鼠胰臟胰島素分泌之研究
The Studies of Rosiglitazone on Insulin Secretion in Glucosamine-Induced Desensitization Rat Pancreas
作者: 何威成
Ho, Wei-Cheng
關鍵字: non-insulin-dependent diabetes mellitus
非胰島素依賴型糖尿病
NIDDM
insulin resistance
胰島素抗性
出版社: 獸醫學系
摘要: 胰臟β細胞分泌胰島素之功能、及胰島素接受器的作用有缺損為造成非胰島素依賴型糖尿病(non-insulin-dependent diabetes mellitus, NIDDM)的兩大主因。目前的研究指出hexosamine生化合成途徑所產生之代謝產物glucosamine為造成胰島素抗性(insulin resistance)之發生、及減弱葡萄糖刺激胰臟β細胞胰島素分泌的主要因素。為誘發一良好的擬糖尿病大白鼠模式,以利於糖尿病治療藥物之研究,實驗將不同濃度的glucosamine(5、10及20 mM)灌流入大白鼠胰臟,結果發現glucosamine可直接抑制大白鼠胰臟β細胞基礎胰島素之分泌,且其抑制作用與glucosamine之濃度成正比。Rosiglitazone為新一代的抗高血糖thiazolidinedione類藥物,其主要的作用主為活化核內接受器(peroxisome proliferator-activated receptor γ, PPAR-γ)而增加肝臟、肌肉、及脂肪組織對胰島素的敏感性,促進胰島素之作用而降低血糖。本實驗室於2001年報告rosiglitazone可直接刺激健康大白鼠之胰臟而促進胰島素之分泌,因此,為了探討rosiglitazone對glucosamine所誘發出的擬第2型糖尿病之影響,實驗先以藥物glucosamine活體灌流大白鼠胰臟,以誘發擬第2型糖尿病的大白鼠,再灌流以4.5 mM之rosiglitazone,並收集由肝門靜脈流出之灌流液後,以競爭性放射性免疫法(radio-immunoassay)測定胰島素之濃度,結果發現rosiglitazone可以增加glucosamine所誘發不敏感化大白鼠基礎胰島素之分泌,而且加強葡萄糖刺激胰島素之分泌。
Type 2 (non-insulin-dependent) diabetes mellitus is a metabolic disorder resulting from lowered pancreatic insulin secretion or insulin action. Recently, the evidence indicated that glucosamine was a product of glucose flux through hexosamine biosynthetic pathway. Glucosamine decreased glucose-induced insulin secreation and produced insulin resistance. In order to obtain a good diabetic animal model for the research of new antidiabetic agents. We perfused rat pancreas with glucosmine(5、10、20 mM). The perfusate collected from portal vein was assayed for deteriming insulin concentration by using radioimmunoassay. The data showed that glucosamine decreased basal insulin secretion and glucose-induced insulin secreation with a dose-dependent manner. The new potent antidiabetic agent rosiglitazone activated peroxisome proliferator-activated receptor γ(PPAR-γ), increased the sensitivity of skeletal muscle, liver and adipose tissue to insulin, and reduced plasma glucose levels. Our paper published in Diabetes showed that rosiglitazone stimulated insulin secretion and potentiated glucose-induced insulin secreation in normal Sprague-Dawley rats. In order to elucidate the direct effect of rosiglitazone on glucosamine-induced mimic type 2 diabetes. Glucosamine-induced type 2 mimic diabetic rats was perfused with 4.5 mM rosiglitazone. The data showed that rosiglitazone enhanced glucose- induced insulin secretion in glucosamine-induced desensitization rat pancreas.
URI: http://hdl.handle.net/11455/13984
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