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CARDIAC FUNCTION IN DIABETES: EFFECTS OF EXERCISE

糖尿病患者的心脏功能：运动的影响

基本信息

批准号：
3446256
负责人：
DENNIS J PAULSON
金额：
$ 4.87万
依托单位：
CHICAGO COLLEGE OF OSTEOPATHIC MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-20 至 1988-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3446256
关键词：
bioenergetics carnitine exercise fatty acid metabolism glucose metabolism heart contraction high energy compound myocardium nuclear magnetic resonance spectroscopy perfusion radiotracer

项目摘要

It is well established that insulin-dependent diabetes in man and animals alters myocardial energy metabolism. These metabolic disturbances are believed to be major factors contributing to the decline in myocardial contractility that occurs in the diabetic heart. The actual mechanism(s) responsible for these metabolic and functional deficits, however, are unclear. The hypothesis of this proposal is that exercise-conditioning will prevent or limit the progressive functional decline of hearts from diabetic animals by effecting specific metabolic adaptations that preserve the functional status of the myocardium. By identifying the beneficial metabolic adaptations that occur in exercised diabetic animals, it will be possible to identify the critical metabolic changes that occur in the diabetic heart which lead to the progressive contractile dysfunction of the myocardium. The results obtained from the proposed studies will also be analyzed to evaluate the potential advisability of exercise-training for diabetic patients. Four groups of rats will be studied: sedentary control, trained control, sedentary diabetic and trained diabetic. Diabetes will be induced by i.v. administration of streptozotocin (50 mg/kg). Rats will be trained on a treadmill for 8 wk. The effects of diabetes and exercise training on cardiac contractility will be studied by measuring in vivo cardiac contractility, and by constructing Frank-Starling curves from isolated perfused working hearts. The vulnerability of the isolated perfused heart to global ischemia will also be assessed. Hearts will be perfused with concentrations of glucose and free fatty acids which characterize the in vivo state. Dynamic changes in high energy phosphate metabolites will be measured using P31-nuclear magnetic resonance spectroscopy. Changes in these metabolites will be correlated to both fatty acid and glucose utilization and tissue concentrations of long-chain acyl carnitine and coenzyme A esters. Preliminary data demonstrated that diabetes results in depressed cardiac function and decreased recovery of cardiac output after ischemia and reperfusion, relative to control hearts. Exercise training of control rats was shown to increase cardiac performance. Hearts from exercise trained rats had elevated cardiac carnitine levels, while diabetic hearts were deficient in carnitine. Carnitine therapy to diabetic rats was shown to prevent the carnitine deficiency and improve the recovery of cardiac output after ischemia and reperfusion. Although the metabolic factors that contribute to the functional disturbances which develop in the diabetic heart have not been elucidated unequivocally, abnormal carnitine metabolism and aberrant substrate utilization implicated as probably sites of action.

众所周知，人类和动物的胰岛素依赖型糖尿病改变心肌能量代谢。这些代谢紊乱是被认为是导致心肌缺血的主要因素。糖尿病患者心脏的收缩性。实际机制然而，导致这些代谢和功能缺陷的是不清楚这一建议的假设是，将防止或限制心脏功能的进行性衰退，糖尿病动物通过影响特定的代谢适应，心肌的功能状态。通过识别有益的运动的糖尿病动物中发生的代谢适应，将是可以确定发生在心脏中的关键代谢变化，糖尿病性心脏病，导致进行性收缩功能障碍，心肌从拟议的研究中获得的结果也将分析了运动训练的潜在可行性，糖尿病患者将研究四组大鼠：久坐对照组、训练对照组、久坐型糖尿病患者和受过训练的糖尿病患者。糖尿病将通过i. v. 链脲佐菌素（50 mg/kg）给药。老鼠将在一个运动训练8 wk。糖尿病和运动训练对糖尿病患者的影响将通过测量体内心脏收缩力来研究心脏收缩力收缩性，并通过构建Frank-Starling曲线从孤立的灌注工作的心脏。离体灌注心脏的脆弱性还将评估对全脑缺血的影响。心中充满了葡萄糖和游离脂肪酸的浓度，其特征在于活体状态高能磷酸盐代谢物的动态变化将是使用P31-核磁共振光谱测量。变化这些代谢物将与脂肪酸和葡萄糖相关长链酰基肉毒碱的利用和组织浓度，辅酶A酯。初步数据表明，糖尿病导致心脏功能低下，缺血后心功能和心输出量恢复减少，再灌注，相对于对照心脏。对照组大鼠运动训练可以提高心脏功能锻炼出的心脏大鼠心脏肉毒碱水平升高，而糖尿病心脏缺乏肉毒碱卡尼汀治疗糖尿病大鼠显示，预防肉毒碱缺乏，促进心输出量恢复缺血再灌注后。虽然代谢因素，导致糖尿病患者的功能紊乱心脏尚未明确阐明，肉毒碱代谢异常和异常的底物利用可能是作用位点。