Influence of intermittent hypoxia interval training on exercise-dependent erythrocyte NOS activation and blood pressure in diabetic patients

Abstract

NOS-activation in erythrocytes (eryNOS) is impaired in patients suffering from type 2 diabetes. We investigated the effect of physical exercise on eryNOS activation and whether 6 week hypoxia interval training may alter this process. Male patients with diabetes mellitus type 2 (NIDDM, n = 12; age, 61.3 ± 8.4 years; BMI, 29.8 ± 3.7 kg/m(2)) underwent physical exercise training before and after 6 week hypoxia interval training. Training was conducted 4 times per week for 90 min at 15.4-12.7 Vol% of inspired oxygen. Vital parameters were recorded. Before hypoxia intervention, eryNOS phosphorylation at serine(1177) decreased significantly during exercise (basal 17.4 ± 12.0 compared with exercise 8.4 ± 9.2 arbitrary grey values (arGV); P < 0.05). After 6 weeks of hypoxia intervention, eryNOS-pSer(1177) (2.2 ± 2.5 arGV) was significantly lower at baseline. Ergometry showed an increase (7.6 ± 3.0 arGV; P < 0.05) followed by a decrease to almost baseline levels after 30 min (3.8 ± 1.5 arGV). Maximal exercise capacity and O(2)-uptake ([Formula: see text] max) increased significantly. The effects were independent from exercise-induced elevation of blood pressure. Exercise-dependent eryNOS phosphorylation at serine(1177) was increased similar to that described for the endothelium in diabetic patients. EryNOS dysregulation was partially restored after intermittent hypoxia training.

Effects of Hypoxia during Continuous and Intermittent Exercise on Glycaemic Control and Selected Markers of Vascular Function in Type 1 Diabetes

“…Recent studies of T2D patients have shown that combining physical exercise with exposure to hypoxia (Hx) (FiO₂ = 14.7 %), a powerful glucose transport stimulator [20][21][22], improves moderate-term (up to 48 h) glycaemic control and insulin sensitivity [20,23]. Moreover, exercise and hypoxia have been shown to increase the activity of erythrocytes' NO synthase (ery-NOS) and to reduce the expression of proinflammatory cytokine -tumor necrosis factor alpha (TNF-α) [24]. Consequently, enhanced NO release, hence vasodilation, and decreased inflammation may preserve or restore vascular function in diabetes [25].…”

Physical exercise associated with NO production: signaling pathways and significance in health and disease

“…Physical exercise enhances NO synthesis in blood vessels through increases in eNOS availability and activity (Brinkmann et al, 2011 ). In patients with type 2 diabetes, 6-week training (90-min exercises 4 times per week) partially restores NOS activity in the erythrocytes (Ladage et al, 2012 ).…”

Moderate intensity exercise in hypoxia increases IGF-1 bioavailability and serum irisin in individuals with type 1 diabetes

“…Ex has been considered to be the main factor stimulating the synthesis of myokine; nevertheless, inflammation and autoimmunity, the factors characterising T1D, may also play a role. 38,52,55 Previous studies have shown that irisin promotes glucose uptake in skeletal muscle, thus improving glucose metabolism. 19,48 In the present study, Exand Hyp-induced increases in serum irisin were observed in parallel with significant BG decrease in T1D patients and considered as a positive observation.…”

“…37 A study by Hall et al demonstrated that 40 min of continuous Ex at moderate intensity (50% lactate threshold: LAT), as well as high intensity (120% LAT) intermittent (4 × 5 min intermittent with 5 min rest) Ex during Hyp, improved glycaemia and had beneficial effects on the concentrations of selected markers of vascular function in patients with T1D. 34 Furthermore, Ex with Hyp contributed to reducing serum levels of proinflammatory cytokine tumour necrosis factor alpha (TNF-α), 34,38 and increased the activity of erythrocytes NO synthase levels in patients with T1D, 38 potentially leading to beneficial changes in skeletal muscle oxygen capacity. These benefits were also observed in animal studies, where the exposure of rats with streptozotcin-induced T1D to hypobaric Hyp increased capillarity, reduced tissue injury and helped maintain glucose homeostasis.…”