Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, Kansas 66160-7601, USA.
J Appl Physiol (1985). 2012 Sep 1;113(5):817-26. doi: 10.1152/japplphysiol.01626.2011. Epub 2012 Jul 12.
One of the fundamental biochemical defects underlying the complications of diabetic cardiovascular system is elevation of diacylglycerol (DAG) and its effects on protein kinase C (PKC) signaling. It has been noted that exercise training attenuates poor cardiac performance in Type 1 diabetes. However, the role of PKC signaling in exercise-induced alleviation of cardiac abnormalities in diabetes is not clear. We investigated the possibility that exercise training modulates PKC-βII signaling to elicit its beneficial effects on the diabetic heart. bio-breeding diabetic resistant rats, a model reminiscent of Type 1 diabetes in humans, were randomly assigned to four groups: 1) nonexercised nondiabetic (NN); 2) nonexercised diabetic (ND); 3) exercised nondiabetic; and 4) exercised diabetic. Treadmill training was initiated upon the onset of diabetes. At the end of 8 wk, left ventricular (LV) hemodynamic assessment revealed compromised function in ND compared with the NN group. LV myocardial histology revealed increased collagen deposition in ND compared with the NN group, while electron microscopy showed a reduction in the viable mitochondrial fraction. Although the PKC-βII levels and activity were unchanged in the diabetic heart, the DAG levels were increased. With exercise training, the deterioration of LV structure and function in diabetes was attenuated. Notably, improved cardiac performance in training was associated with a decrease in myocardial DAG levels in diabetes. Exercise-induced benefits on cardiac performance in diabetes may be mediated by prevention of an increase in myocardial DAG levels.
糖尿病心血管系统并发症的基本生化缺陷之一是二酰基甘油 (DAG) 的升高及其对蛋白激酶 C (PKC) 信号的影响。已经注意到,运动训练可减轻 1 型糖尿病患者的心脏功能不良。然而,PKC 信号在运动诱导的糖尿病心脏异常缓解中的作用尚不清楚。我们研究了运动训练是否可以调节 PKC-βII 信号,以发挥其对糖尿病心脏的有益作用。生物繁殖糖尿病抵抗大鼠,一种类似于人类 1 型糖尿病的模型,被随机分为四组:1)不运动的非糖尿病组(NN);2)不运动的糖尿病组(ND);3)运动的非糖尿病组;和 4)运动的糖尿病组。糖尿病发作后开始进行跑步机训练。在 8 周结束时,左心室(LV)血流动力学评估显示 ND 组的功能受损比 NN 组。LV 心肌组织学显示 ND 组的胶原沉积增加,而电子显微镜显示存活的线粒体分数减少。尽管糖尿病心脏中的 PKC-βII 水平和活性没有改变,但 DAG 水平增加。通过运动训练,糖尿病中 LV 结构和功能的恶化得到了缓解。值得注意的是,糖尿病患者心肌 DAG 水平的降低与心脏功能的改善有关。运动对糖尿病患者心脏功能的益处可能是通过防止心肌 DAG 水平升高来介导的。