CARDIAC FUNCTION IN DIABETES: EFFECTS OF EXERCISE

众所周知，人和动物中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 被认为是导致心肌梗死人数下降的主要因素 糖尿病患者心脏的收缩能力。实际机制(S) 然而，对这些代谢和功能缺陷负有责任的是 不清楚。这项建议的假设是运动条件反射 会阻止或限制心脏功能的进行性衰退 通过影响特定的代谢适应来保护糖尿病动物 心肌的功能状态。通过确定受益的 在运动糖尿病动物中发生的代谢适应，它将是 有可能找出发生在 糖尿病心脏，导致进行性收缩功能障碍 心肌。从拟议研究中获得的结果也将是 分析评价运动训练的潜在可取性 糖尿病患者。 将对四组大鼠进行研究：安静对照组、训练对照组、 久坐的糖尿病患者和训练有素的糖尿病患者。静脉注射会诱发糖尿病。 链脲佐菌素(50 mg/kg)。老鼠将被训练成一只 跑步机跑8周。糖尿病和运动训练对糖尿病的影响 将通过测量活体心脏来研究心脏的收缩能力 收缩性，并通过构建Frank-Starling曲线 灌流的工作心脏。孤立的灌流心脏的脆弱性 也将对全球缺血进行评估。我的心将会充满 葡萄糖和游离脂肪酸的浓度是In的特征 活体状态。高能磷酸盐代谢产物的动态变化将是 使用p31-核磁共振波谱进行测量。中的更改 这些代谢物将与脂肪酸和葡萄糖相关。 长链酰基肉碱和组织浓度的利用和组织浓度 辅酶A酯。 初步数据显示，糖尿病会导致心脏压抑 缺血后心输出量的功能和恢复减退 再灌流，相对于对照心脏。运动训练对对照组大鼠的影响 被证明可以提高心脏功能。锻炼过的心脏 大鼠心脏肉碱水平升高，而糖尿病心脏 缺乏肉碱的。肉碱对糖尿病大鼠的治疗显示 预防肉碱缺乏症，促进心输出量恢复 缺血再灌流后。尽管新陈代谢因素 导致糖尿病患者的功能障碍 心脏尚未明确阐明，肉碱代谢异常 而异常的底物利用可能是作用的部位。

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.