Exercise Training Prevents Coronary Endothelial Dysfunction in Type 2 Diabetic Mice

Abstract

Type 2 diabetes (T2D) is a leading risk factor for cardiovascular diseases including atherosclerosis and coronary heart disease. Exercise training (ET) is thought to have a beneficial effect on these disorders, but the basis for this effect is not fully understood. Because endothelial dysfunction plays a key role in the pathological events leading to cardiovascular complications in T2D, we hypothesized that the effects of ET will be evidenced by improvements in coronary endothelial function. To test this hypothesis, we assessed the effects of ET on vascular function of diabetic (db/db, Leprdb) mice by evaluating endothelial function of isolated coronary arterioles of wild-type (WT) and db/db mice with/without ET. Although dilation of vessels to the endothelial-independent vasodilator, sodium nitroprusside was not different between db/db and WT, dilation to the endothelial-dependent agonist, acetylcholine (ACh), was impaired in db/db compared to WT mice. Vasodilation to ACh was restored in db/db with ET and insulin sensitivity was improved in the db/db after ET. Exercise did not change body weight of db/db, but superoxide dismutase (SOD1 and SOD2) and phosphorylated- eNOS protein (Ser1177) expression in heart tissue was up-regulated whereas tumor necrosis factor-alpha (TNF-α) protein level was decreased by ET. Serum level of interleukin-6 (IL-6) was higher in db/db mice but ET decreased IL-6. This suggests that ET may improve endothelial function by increasing nitric oxide bioavailability as well as decreasing chronic inflammation. We suggest this connection may be the basis for the benefit of ET in T2D.

Impact of cardiac rehabilitation and exercise training programs in coronary heart disease

“…80 These molecules attenuate BP by suppressing noradrenaline and endothelin-1, and improving endothelial responsiveness and function. 81,82 ET also protects against oxidative stress, leading to lower nitric oxide scavenging by oxidation and higher nitric oxide bioavailability which have anti-hypertensive effects. 83 ET-induced improvements in managing oxidative stress help lower systemic inflammatory markers in physically active people with CHD.…”

Protective effect of crocin and voluntary exercise against oxidative stress in the heart of high-fat diet-induced type 2 diabetic rats

“…A part of the protective effect of physical exercise has been hypothesized to derive from antioxidant effects. Lee et al (29) reported that exercise training could improve coronary vascular function by suppressing oxidative stress in a type 2 diabetes. Kupai et al (26) showed the cardioprotective effect of voluntary exercise in the Goto-Kakizaki type 2 diabetic rat heart against IR injury.…”

Role of Von Willebrand Factor in Type 2 Diabetes Mellitus Patients

“…7,8,9 Endothelial dysfunction is known to occur in type 2 Diabetes Mellitus (DM), which plays a critical role in the development of atherosclerosis, a process that occurs prematurely and at an accelerated rate in diabetic patients. 10,11,12 Vascular endothelium damage is characterised by an increase in the plasma levels of endothelial markers like von Willebrand factor (vWF), Cellular Adhesion Molecules (CAD), endothelin 1 (ET1), plasminogen l activator inhibitor type-1 (PAI-1), selectin, thrombomodulin. These markers may be useful to investigate early endothelium involvement.…”