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系統識別號 U0026-0812200914261180
論文名稱(中文) 長期運動訓練與胰島素治療對第一型糖尿病鼠由胰島素及類胰島素生長因子-1所媒介之血管功能的影響
論文名稱(英文) Effects of Long-term Exercise Training and Insulin Treatment on Insulin- and Insulin-like Growth Factor-1-mediated Vascular Function in Type 1 Diabetic Rats
校院名稱 成功大學
系所名稱(中) 物理治療研究所
系所名稱(英) Department of Physical Therapy
學年度 96
學期 2
出版年 97
研究生(中文) 傅耕業
研究生(英文) Keng-Yeh Fu
電子信箱 t6604108@mail.ncku.edu.tw
學號 t6694108
學位類別 碩士
語文別 英文
論文頁數 81頁
口試委員 指導教授-楊艾倫
口試委員-林尊湄
口試委員-李信達
中文關鍵字 運動訓練  第一型糖尿病  類胰島素生長因子-1  胰島素 
英文關鍵字 Insulin  IGF-1  exercise training  type 1 diabetes mellitus 
學科別分類
中文摘要 背景及目的:目前已知胰島素(insulin)與類胰島素生長因子-1 (insulin-like growth factor-1, IGF-1)可經由內皮細胞產生一氧化氮(nitric oxide, NO)而達到血管舒張的作用。許多研究顯示,運動訓練與胰島素治療皆可藉由增加體內一氧化氮的生物可用性(bioavailability)改善血管的功能,然而,長期運動訓練與胰島素治療對於第一型糖尿病由胰島素與類胰島素生長因子-1所誘發之血管功能的影響,至今仍舊未知。因此,本篇研究利用第一型糖尿病動物模式,探討長期運動訓練與胰島素治療對於胰島素與類胰島素生長因子-1所誘發血管功能的影響及其潛在機制。
方法:將雄性Wistar大鼠隨機分為控制組(Con)、糖尿病組(DM)、糖尿病加運動訓練組(DM+Ex)、及糖尿病加胰島素治療組(DM+IT)。本篇研究利用濃度為六十五毫克/公斤的streptozocin (STZ),經由股靜脈注射來誘發第一型糖尿病。誘發成功後,將糖尿病加運動訓練組置於跑步機上進行八週中度運動訓練,每週五天,每天持續六十分鐘;而糖尿病加胰島素治療組則接受每天一次的胰島素治療,治療濃度為二十至四十單位/公斤/天,亦為期八週。待實驗過程結束後,將每組大鼠的胸主動脈取下,分別測量血管對於胰島素、類胰島素生長因子-1、乙醯膽鹼(acetylcholine, ACh)、以及sodium nitroprusside (SNP)的血管舒張反應。此外,我們藉由phosphatidylinositol 3-kinase (PI3-K)及endothelial nitric oxide synthase (eNOS)抑制劑的介入,探討這兩種酶在其中所扮演的角色。
結果:我們發現:一)在糖尿病組中,由胰島素與類胰島素生長因子-1所誘發之血管舒張反應明顯較控制組為差(P<0.05);二)經由八週的運動訓練和胰島素治療,皆可顯著地改善糖尿病鼠由胰島素與類胰島素生長因子-1所誘發血管舒張反應較差的情形(P<0.05);三)各組中胰島素與類胰島素生長因子-1所誘發血管舒張反應的差別,主要是透過改變PI3-K與eNOS的活性來調節;四)在糖尿病組中,由乙醯膽鹼所誘發之血管舒張反應明顯較控制組為差,而八週運動訓練與胰島素治療皆可有效地改善糖尿病鼠血管舒張反應較差的情形,此部分結果與先前的研究結論一致;五)由SNP所誘發之血管舒張反應在各組間無顯著差別。
結論:以上結果顯示,第一型糖尿病鼠體內由胰島素與類胰島素生長因子-1所誘發的血管舒張反應明顯較正常鼠為差,經由長期的運動訓練和胰島素治療皆可有效地增進血管功能;而此二者治療的效果主要是透過PI3-K與eNOS活性的改變來調節。
英文摘要 Background and Purpose: Insulin and insulin-like growth factor-1 (IGF-1) have potent vasorelaxation effect via the production of endothelium-derived nitric oxide (EDNO). Accumulating evidences have indicated that both exercise training and insulin treatment improve vascular function by increasing EDNO bioavailability. However, few studies focus on the effects of these interventions on vascular responses mediated by insulin and IGF-1 in type 1 diabetic status. Therefore, the aim of the present study was to investigate the effects of long-term exercise training and insulin treatment on insulin- and IGF-1-mediated vascular function in type 1 diabetic status.
Methods: Male Wistar rats were randomly divided into the non-diabetic control (Con), the diabetic (DM), the diabetes with exercise training (DM+Ex), and the diabetes with insulin treatment (DM+IT) groups. Type 1 diabetes mellitus was induced by the intravenous injection of streptozotocin (65 mg/kg). The DM+Ex group performed an 8-week, moderate-intensity treadmill exercise program for 60 min/day, 5 day/week. The DM+IT group received a daily insulin treatment for 8 weeks with the gradually increased dose from 20 to 40 U/kg/day. At the end of experiments, the vasorelaxation responses to insulin, IGF-1, acetylcholine (ACh), and sodium nitroprusside (SNP) in thoracic aortas were evaluated among four groups. In addition, the roles of phosphatidylinositol 3-kinase (PI3-K) and endothelial NO synthase (eNOS) in the vasorelaxation responses were examined.
Results: We found that 1) insulin- and IGF-1-mediated vasorelaxation was significantly impaired in the DM group compared with that in the Con group (P<0.05); 2) both exercise training and insulin treatment significantly ameliorated these impaired vascular responses to insulin and IGF-1 in the DM+Ex and the DM+IT groups (P<0.05); 3) the alternations of vascular responses to insulin and IGF-1 were mainly due to the altered activities of PI3-K and eNOS; 4) consistent with previous studies, ACh-mediated vasorelaxation was impaired in the DM group, whereas exercise training and insulin treatment reversed the impaired vascular response in the DM+Ex and the DM+IT groups; 5) no significant difference was found in SNP-mediated vasorelaxation among four groups.
Conclusions: Our results indicated that insulin- and IGF-1-mediated vasorelaxation responses were impaired in type 1 diabetic status; whereas the exercise training and insulin treatment effectively reversed these vascular impairments. The benefits of both interventions were mainly due to the increased release of PI3-K and eNOS in the NO-dependent pathway.
論文目次 Abstract ------------------------------------------- 1
Abstract in Chinese ------------------------------- 3
Introduction -------------------------------------- 5
Materials ----------------------------------------- 15
I. Preparation of drugs ------------------------ 15
Methods ------------------------------------------- 20
I. Experimental animals --------------------- 20
II. Induction of diabetes mellitus ----------- 20
III. Exercise training protocol --------------- 21
IV. Insulin treatment ------------------------ 22
V. Measurement of blood glucose level ------- 23
VI. Assay of citrate synthase activity ------- 23
VII. Preparation of vessels ------------------- 25
VIII. Measurement of vasorelaxation ------------ 26
IX. Statistical analysis --------------------- 27
Results ------------------------------------------- 29
I. Body weight and blood glucose level ------ 29
II. Citrate synthase activity ---------------- 29
III. Acute effect of insulin treatment on glycemic
control ---------------------------------- 30
IV. Concentrate-dependent responses to insulin and
IGF-1 ------------------------------------ 30
V. Concentrate-dependent responses to ACh --- 31
VI. Roles of PI3-K and eNOS in the vasorelaxation
responses mediated by insulin and IGF-1 -- 32
VII. Roles of PI3-K and eNOS in the vasorelaxation
responses mediated by ACh ---------------- 33
VIII. SNP-mediated vasorelaxation -------------- 34
Discussion ---------------------------------------- 36
Tables -------------------------------------------- 47
Figures ------------------------------------------- 48
References ---------------------------------------- 64
Appendix ------------------------------------------ 79
Biographic note ----------------------------------- 81
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