Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/13925
標題: Sulfonylureas對高脂飼料誘導肥胖大白鼠胰臟胰島素分泌之影響
The effect of sulfonylureas on insulin secretion in high-fat diet induced fatty rats
作者: 張家嘉
Chang, Chia Chia
關鍵字: Type 2 diabetes
第2型糖尿病
High-fat diet
insulin
Sulfonylureas
高脂飼料
胰島素
Sulfonylureas
出版社: 獸醫學系
摘要: 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。
Type 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.
URI: http://hdl.handle.net/11455/13925
Appears in Collections:獸醫學系所

文件中的檔案:

取得全文請前往華藝線上圖書館



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.