急性游泳运动对糖尿病大鼠脂肪组织—胰岛轴的影响及其中枢机理初探
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摘要
糖尿病是一种常见的有遗传倾向的代谢内分泌疾病。1 型糖尿病约占糖尿病患者总数的10％，常发生于儿童和青少年，严重危害人类健康。随着人们生活水平的提高和体力活动的减少，糖尿病患者逐年增加，糖尿病日益成为继肿瘤和心血管疾病之后威胁人健康的第三杀手。因此，防治糖尿病成为提高身体健康的重要研究课题。运动是治疗和预防糖尿病的有效手段之一，可以改善糖尿病能量代谢紊乱的症状，但是国内1型糖尿病患者运动治疗开展非常有限，相关研究尚属空白。本研究观察了急性游泳运动对糖尿病大鼠血Leptin、胰岛素和下丘脑Leptin受体表达的影响，来探讨运动对糖尿病大鼠脂肪组织—胰岛轴的影响以及对可能的中枢调控机制进行初步探讨。
实验动物为雄性Sprague-Dawley大鼠96只，分为正常组和糖尿病组，每一组又分为对照非运动组、运动后即刻组、运动后1小时组、运动后3小时组、运动后6小时和运动后12小时组。以60mg/kg体重剂量腹腔注射链脲佐菌素(STZ)复制1型糖尿病模型。运动方式为一次性60分钟游泳运动，尾部负重3％体重。血糖浓度用自动生化分析仪测定，血清胰岛素和Leptin浓度用放免法测定，下丘脑做免疫组化冰冻切片染色观察。
研究结果：①STZ诱导的糖尿病大鼠血清胰岛素水平、血清Leptin浓度与正常大鼠比显著性下降(p＜0.05)，血糖显著性升高(p＜0.05)。②急性游泳运动对正常大鼠和STZ糖尿病大鼠血清胰岛素
急性游泳运动对糖尿病大鼠脂肪组织一胰岛轴的影响及其中枢机理初探王海英
水平影响的趋势相同，在运动后1小时下降最快(正常组p<0 .05，糖
尿病组p<0.01);运动后12小时均恢复到了对照组水平。将血胰岛素、
血LePtin进行百分比比较，发现急性游泳运动对STZ糖尿病大鼠血胰
岛素、血LePtin影响变化较大，但是对脂肪组织一胰岛轴的调节能力
影响不大。提示运动可以部分改善血胰岛素和L即tin的相互调节作用。
③对STZ糖尿病大鼠运动后血清胰岛素浓度和LePtin浓度、血清胰岛
素浓度和下丘脑LePtin受体表达、血清LePtin浓度和下丘脑Lept in
受体表达进行相关分析，发现大鼠血清胰岛素浓度和LePtln浓度呈显
著中度正相关((R=0.61，P二0.019正常大鼠;R=0.59，P=0.022糖尿病大
鼠);血清胰岛素浓度和下丘脑Lept in受体表达负相关(正常大鼠
r=一0.84，p=0.033;糖尿病大鼠r==一0.34，p=0.049)。
主要结论:①在STz诱导的糖尿病状态下，胰岛素分泌减少，生理功
能下降，血糖升高。急性有氧游泳运动可以提高正常大鼠和糖尿病大鼠的
胰岛素敏感指数，充分发挥胰岛素降血糖的生理功能。②急性游泳运动
可以降低正常大鼠和STZ糖尿病大鼠血胰岛素、血LePtin水平，血胰岛
素是影响血LePtin的主要因素。急性游泳运动对脂肪组织一胰岛轴的调
节能力影响不大。③急性游泳运动可以提高大鼠下丘脑L即tin受体的表
达，运动可能促进血L即tin向下丘脑转运，L即tin与下丘脑受体结合
后间接影响脂肪组织一胰岛轴。④急性游泳运动对糖尿病大鼠脂肪缉织
一胰岛轴的改善作用有时相性的变化，要想通过运动改善糖尿病症状，
必须持之以恒、坚持科学的锻炼。
Diabetes is a disease in which the body does not produce or properly use insulin. As many as 10% of people with diabetes is Type 1 diabetes. Type 1 diabetes is usually diagnosed in children and young adults, and was previously known as juvenile diabetes. Diabetes can damage the kidneys , heart, eyes and skin. At present, the incidence of diabetes are increasing year by year, and it is becoming one of the most common human health problem in the world. Diabetes mellitus is called the third killer following cardiovascular disease and cancer. As a method to treat and prevent diabetes, aerobic exercise has been accepted extensively. The purpose of the present study is to investigate the effect of acute aerobic exercise on insulin , letpin and leptin-receptor in hypothalamus of STZ rats , probing the ameliorate of acute aerobic exercise on adipo-insular axle and the possible central mechanism.
In a randomized, 96 male SD rats were divided into 2 groups : diabetes and control. Blood samples were collected after exercise. Insulin and leptin were measured by radioimmunoassay and leptin-receptor expression in hypothalamus were measured by immuohistochemistry.
Results: (1) The STZ rats showed low plasma glucose, high insulin and leptin contrasting the control rats. (2) Plasma insulin and leptin were reduced after exercise, but resumed to the control level after 12 hours of exercise.?we fund that plasma insulin and leptin is remarkable positive relevance and plasma insulin and leptin receptor expression in hypothalamus is negative relevance.
Conclusion: (1)Acute aerobic exercise can up-regulate insulin sensitive index. (2) Acute aerobic exercise can down-regulate plasma insulin and leptin ,and plasma insulin is the important influence factor for plasma letpin. (3)Acute aerobic exercise have periodic up-regulation effect on hypothalamus leptin-receptor expression during exercise. Therefore we speculate that hypothalamus might regulate adipo-insular axle by adjusting leptin-receptor expression level.
实验动物为雄性Sprague-Dawley大鼠96只，分为正常组和糖尿病组，每一组又分为对照非运动组、运动后即刻组、运动后1小时组、运动后3小时组、运动后6小时和运动后12小时组。以60mg/kg体重剂量腹腔注射链脲佐菌素(STZ)复制1型糖尿病模型。运动方式为一次性60分钟游泳运动，尾部负重3％体重。血糖浓度用自动生化分析仪测定，血清胰岛素和Leptin浓度用放免法测定，下丘脑做免疫组化冰冻切片染色观察。
研究结果：①STZ诱导的糖尿病大鼠血清胰岛素水平、血清Leptin浓度与正常大鼠比显著性下降(p＜0.05)，血糖显著性升高(p＜0.05)。②急性游泳运动对正常大鼠和STZ糖尿病大鼠血清胰岛素
急性游泳运动对糖尿病大鼠脂肪组织一胰岛轴的影响及其中枢机理初探王海英
水平影响的趋势相同，在运动后1小时下降最快(正常组p<0 .05，糖
尿病组p<0.01);运动后12小时均恢复到了对照组水平。将血胰岛素、
血LePtin进行百分比比较，发现急性游泳运动对STZ糖尿病大鼠血胰
岛素、血LePtin影响变化较大，但是对脂肪组织一胰岛轴的调节能力
影响不大。提示运动可以部分改善血胰岛素和L即tin的相互调节作用。
③对STZ糖尿病大鼠运动后血清胰岛素浓度和LePtin浓度、血清胰岛
素浓度和下丘脑LePtin受体表达、血清LePtin浓度和下丘脑Lept in
受体表达进行相关分析，发现大鼠血清胰岛素浓度和LePtln浓度呈显
著中度正相关((R=0.61，P二0.019正常大鼠;R=0.59，P=0.022糖尿病大
鼠);血清胰岛素浓度和下丘脑Lept in受体表达负相关(正常大鼠
r=一0.84，p=0.033;糖尿病大鼠r==一0.34，p=0.049)。
主要结论:①在STz诱导的糖尿病状态下，胰岛素分泌减少，生理功
能下降，血糖升高。急性有氧游泳运动可以提高正常大鼠和糖尿病大鼠的
胰岛素敏感指数，充分发挥胰岛素降血糖的生理功能。②急性游泳运动
可以降低正常大鼠和STZ糖尿病大鼠血胰岛素、血LePtin水平，血胰岛
素是影响血LePtin的主要因素。急性游泳运动对脂肪组织一胰岛轴的调
节能力影响不大。③急性游泳运动可以提高大鼠下丘脑L即tin受体的表
达，运动可能促进血L即tin向下丘脑转运，L即tin与下丘脑受体结合
后间接影响脂肪组织一胰岛轴。④急性游泳运动对糖尿病大鼠脂肪缉织
一胰岛轴的改善作用有时相性的变化，要想通过运动改善糖尿病症状，
必须持之以恒、坚持科学的锻炼。
Diabetes is a disease in which the body does not produce or properly use insulin. As many as 10% of people with diabetes is Type 1 diabetes. Type 1 diabetes is usually diagnosed in children and young adults, and was previously known as juvenile diabetes. Diabetes can damage the kidneys , heart, eyes and skin. At present, the incidence of diabetes are increasing year by year, and it is becoming one of the most common human health problem in the world. Diabetes mellitus is called the third killer following cardiovascular disease and cancer. As a method to treat and prevent diabetes, aerobic exercise has been accepted extensively. The purpose of the present study is to investigate the effect of acute aerobic exercise on insulin , letpin and leptin-receptor in hypothalamus of STZ rats , probing the ameliorate of acute aerobic exercise on adipo-insular axle and the possible central mechanism.
In a randomized, 96 male SD rats were divided into 2 groups : diabetes and control. Blood samples were collected after exercise. Insulin and leptin were measured by radioimmunoassay and leptin-receptor expression in hypothalamus were measured by immuohistochemistry.
Results: (1) The STZ rats showed low plasma glucose, high insulin and leptin contrasting the control rats. (2) Plasma insulin and leptin were reduced after exercise, but resumed to the control level after 12 hours of exercise.?we fund that plasma insulin and leptin is remarkable positive relevance and plasma insulin and leptin receptor expression in hypothalamus is negative relevance.
Conclusion: (1)Acute aerobic exercise can up-regulate insulin sensitive index. (2) Acute aerobic exercise can down-regulate plasma insulin and leptin ,and plasma insulin is the important influence factor for plasma letpin. (3)Acute aerobic exercise have periodic up-regulation effect on hypothalamus leptin-receptor expression during exercise. Therefore we speculate that hypothalamus might regulate adipo-insular axle by adjusting leptin-receptor expression level.
引文
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[2]. Zhang YY et al. Positional .cloning of the mouse obese gene and its human homoloue [J].Nature, 1994,372:425-432.
[3]. Caro JF, Madhur KS,Jezzy WK,et al. Leptin: the tale of an obesity gene Diabets, 1996,45:1455-62.
[4]. Collins S. Role of leptin in fat regulation. Nature, 1996,380:677-81.
[5]. Collins S,Surwit RS. Pharmacologic Manipulation of ob Expression in a Dietary Model of Obesity .Bio Chem, 1996,271:9437-40.
[6]. Friedman JM, Halas JL. Leptin and the regulation of body weight in mammals. Nature 1998,395: 763.
[7]. White DW. Tartaglia LA. Leptin and OB-R :body weight regulation by a cytokine receptor .Cytokine Growth Factor Rev ,1996,7(4):303-9.
[8]. YJ Lee, JH Park, et al.Leptin receptor isoform expression in rat osteoblasts and their functional analysis.FEBS Lett, 2002, 528(1-3): 43-7.
[9]. KW Nowak, P Kaezmarek,et al. Rat thyroid gland expresses the long form of leptin receptors, and leptin stimulates the function of the gland in euthyroid non-fasted animals.J Mol Med, 2002, 9(1): 31-4.
[10]. Loatao,M.P.,et al.Presenee of leptin-receptor in rat small intestine and leptin effect on sugar absorption,FEBS Lett., 1998,423(3):302-306.
[11]. Agata J,Masuda A, et al. High plasma immunoreactive leptin level in essential hypertension. [J].Am J Hypertens, 1997, 10:1171-1174.
[12]. Hirose H, Saito I,et al.The obese gene product,leptin:possible role in obesity-related hypertension inadolescents.[J]. Hypertens, 1998, 16:2007-2012.
[13]. Muller G,Ertl J, Gerl M. Leptin Impairs Metabolic Actions of Insulin in Isolated Rat Adipoeytes [J]. J Biol Chem, 1997,272:10585-10593.
[14]. Leyva F, Godsl and IF, et al. Hyperleptinemia as a Component of a Metabolic Syndrome of Cardiovascular Risk.[J].Arterioseler Thromb Vssc Biod, 1998,18:928-933.
[15]. LeroyP, Expression ofob Gene in Adipose Cells, Dessolin S,Villageois
P, et al.[J] Biol Chem, 1996,271:2365-2368.
[16]. Kolaczynski JW, Nyce MR, Considine RV et al. Acute and chronic effects of insulin on leptin production in humans: studies in vivo and in vitro. Diabetes, 1996,45:699-701.
[17]. Flier JS. Leptin expression and action: new experimental paradigms. Proc Natl Acad Sci USA ,1997,94:4242-4245.
[18]. Considine, RV, Nyce MR, et al.Dexamethasone stimulates leptin release from human adipocytes: unexpected inhibition by insulin. [J]. Cell Biochem, 1997,65: 254-258.
[19]. Taragalia LA,Dembski M,Weng X et al. Identification and expression cloning of a leptin receptor, OB-R.Cell, 1995,83:1269-1271.
[20]. Russell, CD, Petersen RN, et al.Leptin expression in adipose tissue from obese humans: depot-specific regulation by insulin and dexamethasone. Am J Physiol Endocrinol Metab 1998,275:E507-E515.
[21]. Halleux, CM, Servais I,et al. Multihormonal control of ob gene expression and leptin secretion from cultured human visceral adipose tissue: increased responsiveness to glucocorticoids in obesity. J Clin Endocrinol Metab, 1998,83:902-910.
[22]. Bradley, RL, and Cheatham B. Regulation of ob gene expression and leptin secretion by insulin and dexamethasone in rat adipocytes. Diabetes, 1999,48: 272-278.
[23]．高维纬．运动对糖、脂代谢的影响，[J]现代康复，2001，5(1)：11-13．
[24]. D Dunger, L Ahmed, and K Ong .Growth and body composition in type 1 diabetes mellitus.Horm Res, January 1, 2002; 58 Suppl 1:66-71..
[25]. Wabitsch M,Blum WF, Muehe R, et al.Contdbution od androgens to the gender diffrence in leptin production in obese children and adolescents .J Clin Invest, 1997,100:808.
[26]. Saad MF. Changes in plasma leptin during the menstrual cycle.Eur J Endocrinol. 1998,139(5):528-31.
[27]. Levin N, Nelson C. Decreased food intake does not completely account
for adiposity reduction after ob protein infusion. Proc Natl Acad Sci U S A, 1996,20(4): 1726-1730.
[28]. Eriksson KF, Lindgarde F. Prevention of Type Ⅱ (non-insulin dependendent) diabetes mellitus by diet and physical exercise:the 6-year Malmo feasibility study [J]. Diabetolgy, 1991,(34):891.
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