Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/13925
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dc.contributor.advisor楊繼zh_TW
dc.contributor.advisorChi Yangen_US
dc.contributor.author張家嘉zh_TW
dc.contributor.authorChang, Chia Chiaen_US
dc.date2004zh_TW
dc.date.accessioned2014-06-06T06:51:27Z-
dc.date.available2014-06-06T06:51:27Z-
dc.identifier.urihttp://hdl.handle.net/11455/13925-
dc.description.abstract第2型糖尿病是一種代謝異常的疾病,常伴隨周圍胰島素阻抗及β細胞胰島素分泌不良的情形,而肥胖則被認為是誘發第2型糖尿病的主要風險因子,且增加發生胰島素阻抗的風險。Sulfonylureas是現今常用來治療糖尿病的降血糖藥物,其作用為關閉ATP-dependent K+ (KATP) channel,造成細胞膜的毀極化,而發生鈣離子依賴型的胰島素分泌。本實驗即是將sulfonylureas(glipizide及gliclazide)併加或不加葡萄糖灌流入正常或高脂餵飼10週的大白鼠胰臟,比較兩者間刺激胰島素分泌的情形。首先可以發現,高脂餵飼大白鼠的平均體重明顯的大於正常餵飼組(p < 0.05),且高脂餵飼組的血糖平均值較高,但與正常餵飼組間並無顯著之差異。灌流結果顯示,在高脂餵飼組中,餵食高脂飼料8週之後,胰島對葡萄糖刺激胰島素分泌的反應有逐漸下降的趨勢。而在正常餵飼組中,glipizide(1 mM)比gliclazide (1 mM)具有較佳刺激胰島素分泌的能力,且glipizide在0.01-0.1 mM的濃度下,其刺激作用呈劑量反應關係。Glipizide(0.01 mM)會增加10 mM葡萄糖刺激胰島素分泌的能力。但若glipizide 與1 mM葡萄糖併用則無法促進胰島素之分泌。而glipizide在高脂餵飼組也有類似之情形。兩者相比較,可以發現高脂餵飼組對於glipizide或glipizide併加葡萄糖灌流的反應,比起正常的老鼠,皆有下降的趨勢。但與正常老鼠單獨給予 10 mM葡萄糖刺激相比較,仍會增加促進胰島素分泌的能力。故由實驗推測高脂餵飼會降低β細胞的功能,但glipizide仍會促進整體胰島素之分泌。zh_TW
dc.description.abstractType 2 diabetes mellitus is a metabolic disorder accompanied by insulin resistance in peripheral tissues and a progressive decline in β cells function. In addition, obesity is a major risk factor for the development of insulin resistance and type 2 diabetes mellitus. Sulfonylureas are widely used in treatment of patients with non-insulin-dependent diabetes mellitus by a closure of ATP-dependent K+ channels, depolarization membrane, and stimulation Ca2+ entry through voltage-gated Ca2+ channels and induction of insulin secretion. In these studies, sulfonylureas (glipizide and gliclazide) with or without glucose were used to perfuse the pancreas of rats fed with normal diet or high fat diet for 10 weeks. The body weights of Sprague- Dowley rats fed with high fat diet were significantly heavier than the rats fed with normal diet (p<0.05). But the difference of blood glucose concentrations was not significantly between the two treatment groups. The results showed that glucose (10 mM) -induced insulin secretion was decreased after fed with high fat diet for 8 weeks. In the rats fed with normal diet, glipizide (1 μM) stimulated a higher insulin secretion than gliclazide (1 μM). In addition, glipizide from 0.01-1.0μM stimulated insulin secretion in a dose dependent manner. Glipizide at 0.01μM also potentiated the glucose (10 mM)-induced insulin secretion. However, glipizide in Krebs-Ringer bicarbonate(KRB) perfusate containing 1 mM glucose didn't enhance insulin secretion. Compared the stimulation response of glipizide or glipizide with glucose, the insulin secretion response in the rats fed with high fat diet was less than the rats fed with normal diet. But compared with normal diet rats perfused with 10 mM glucose, glipizide with 10 mM glucose still stimulated a higher insulin secretion in the rats fed with high fat diet. These results suggested that rats fed with high fat diet for 10 weeks induced a detrimental response to the β cells function in insulin secretion.en_US
dc.description.tableofcontents中文摘要 ………………………………………………………………i 英文摘要 ………………………………………………………………ii 目錄 ………………………………………………………………iv 圖次 ………………………………………………………………vi 表次 ………………………………………………………………vii 第一章 緒言…………………………………………………………… 1 第二章 文獻探討……………………………………………………… 3 第一節 糖尿病 ………………………………………………………3 第二節 糖尿病的診斷……………………………………………… 4 第三節 胰島素訊息傳導和作用…………………………………… 6 第四節 胰島素之分泌……………………………………………… 9 第五節 肥胖與胰島素阻抗 ………………………………………12 第六節 第2型糖尿病治療藥物之分類 ………………………… 19 第七節 Sulfonylureas…………………………………………… 23 第八節 糖尿病之實驗動物模式建立 ………………………… 32 第三章 材料與方法 ………………………………………………… 38 實驗動物………………………………………………………………38 體重分析………………………………………………………………39 血糖分析………………………………………………………………39 灌流系統………………………………………………………………39 灌流方法………………………………………………………………40 實驗一:Glipizide與gliclazide對正常大白鼠胰臟胰島素分泌 之影響………………………………………………………41 實驗二:不同劑量之glipizide對正常大白鼠胰臟胰島素分泌之 影響…………………………………………………………42 實驗三:Glipizide對葡萄糖刺激胰島素分泌之影響 ……………43 實驗四:葡萄糖對餵食高脂飼料之肥胖大白鼠胰臟胰島素分泌 之影響………………………………………………………44 實驗五:Glipizide對餵食高脂飼料之肥胖大白鼠胰臟胰島素 分泌之影響…………………………………………………44 實驗六:Glipizide對葡萄糖刺激餵食高脂飼料之肥胖大白鼠胰 島素分泌之影響……………………………………………45 胰島素之測定…………………………………………………………46 資料分析與統計………………………………………………………47 第四章 結果……………………………………………………………48 體重分析………………………………………………………………48 血糖分析………………………………………………………………48 實驗一:Glipizide與gliclazide對正常大白鼠胰臟胰島素分泌 之影響………………………………………………………49 實驗二:不同劑量之glipizide對正常大白鼠胰臟胰島素分泌之 影響…………………………………………………………52 實驗三:Glipizide對葡萄糖刺激胰島素分泌之影響…………… 54 實驗四:葡萄糖對餵食高脂飼料之肥胖大白鼠胰臟胰島素分泌 之影響………………………………………………………56 實驗五:Glipizide對餵食高脂飼料之肥胖大白鼠胰臟胰島素 分泌之影響…………………………………………………58 實驗六:Glipizide對葡萄糖刺激餵食高脂飼料之肥胖大白鼠胰 島素分泌之影響……………………………………………60 第五章 討論……………………………………………………………63 第六章 結論……………………………………………………………70 文獻參考 ……………………………………………………………… 71zh_TW
dc.language.isoen_USzh_TW
dc.publisher獸醫學系zh_TW
dc.subjectType 2 diabetesen_US
dc.subject第2型糖尿病zh_TW
dc.subjectHigh-fat dieten_US
dc.subjectinsulinen_US
dc.subjectSulfonylureasen_US
dc.subject高脂飼料zh_TW
dc.subject胰島素zh_TW
dc.subjectSulfonylureaszh_TW
dc.titleSulfonylureas對高脂飼料誘導肥胖大白鼠胰臟胰島素分泌之影響zh_TW
dc.titleThe effect of sulfonylureas on insulin secretion in high-fat diet induced fatty ratsen_US
dc.typeThesis and Dissertationzh_TW
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