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, Lepr(db)) 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.