Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/13939
標題: 5-aminoimidazole-4-carboxamide riboside(AICAR)對大白鼠胰臟分泌胰島素之研究
The Studies of 5-aminoimidazole-4-carboxamide riboside(AICAR) on Insulin
作者: 呂柏賢
Lu, Pao-Hsien
關鍵字: AICAR
胰島素
AMPK
insulin
type 2 diabetes mellitus
rosiglitazone
第二型糖尿病
出版社: 獸醫學系
摘要: Rosiglitazone(RSG)是一種新的thiazolidinedione類降血糖藥品,其作用主為促進周圍組織增加胰島素接受器,從而改善周圍組織對胰島素的阻抗性,所以能促進葡萄糖的利用,改善第二型糖尿病病人之血糖控制。過去藉由大白鼠胰臟之灌流實驗,發現RSG亦能直接促進胰島素之分泌。研究顯示glucosamine(GlcN)可經由hexosamine生化合成途徑誘發胰島素之阻抗、及抑制胰島素之分泌,因此實驗利用GlcN去敏感化以誘發擬第二型糖尿病之大白鼠,並進行胰臟灌流實驗,結果發現RSG可促進GlcN所誘發擬第二型糖尿病大白鼠胰臟胰島素之分泌,事先給予RSG亦可減輕GlcN對胰島素分泌之抑制作用。另由國外研究發現RSG可經由AMP/ATP途徑活化AMP-activated protein kinase (AMPK),從而促進骨骼肌細胞內第4型葡萄糖運輸蛋白轉移至細胞膜上,而促進葡萄糖的利用效率。因此為了探討AMPK活化對胰島素分泌之影響,實驗以AMPK活化劑AICAR (5-Amino-4- Imidazolecarboxamide Riboside)灌流正常大白鼠之胰臟,結果發現AICAR刺激胰臟胰島素之分泌,且其刺殺作用與AICAR之濃度成正比,並且促進GlcN所誘發擬第二型糖尿病大白鼠胰臟胰島素之分泌,因此RSG促進胰島素之分泌反應機轉可能與AMPK的活化有關。
Rosiglitazone(RSG) is a new antidiabetic agent of thiazolidinediones. In the previous studies, RSG increases the expression of glucose-transporters and improves insulin resistance in peripheral tissue. Subsequently, RSG increases the use of glucose and controls the blood glucose concentration in the patients with type 2 diabetes mellitus. In our previous studies, RSG also stimulated insulin secretion in perfused rat pancreas. The evidence indicated that glucosamine(GlcN) is a product of glucose flux through hexosamine biosynthetic pathway. GlcN produces insulin resistance and decreases insulin secretion. By using perfusion of rat pancreas in this study, we found that RSG also increased insulin secretion in GlcN-induced type 2 mimic diabetic rats. The results suggested RSG improved the inhibitory effect of GlcN in insulin secretion. Evidence indicated that RSG activated AMP-activated protein kinase through AMP/ATP pathway, and increased glucose transporters type 4 transformation to cell membrane in skeletal muscle, then increased the use of glucose. In order to elucidate the effect of the activation of AMP kinase on insulin secretion, we perfused rat pancreas with 5-amino-4-imidazolecarboxamine riboside(AICAR) which is a activator of AMP kinase. The results showed that AICAR stimulated insulin secretion in a dose-dependent manner, and AICAR also stimulated insulin secretion in GlcN-induced type 2 mimic diabetic rats. These results suggested that RSG probably increased insulin secretion through the activation of AMP kinase.
URI: http://hdl.handle.net/11455/13939
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