Hypoxia and Hyperoxia Affect Serum Angiogenic Regulators in T2DM Men during Cycling

Abstract

Exercise-induced transient increases in pro-angiogenic regulators can promote angiogenesis.This pilot study aims to analyze the potential of exercise to positively affect angiogenic regulators in patients with type 2 diabetes mellitus (T2DM), who often exhibit abnormal angiogenesis, under different environmental conditions. 9 overweight/obese men with uncomplicated T2DM (8 took anti-diabetic drugs) performed submaximal cycling for 40 min in normoxia (≈21 vol%O), hypoxia (≈14 vol%O) and during alternating hypoxia/hyperoxia (≈14 vol%O/≈30 vol%O, 5-min intervals) (3×3 crossover design). Serum pro-angiogenic vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-9 and anti-angiogenic endostatin were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Non-parametric statistical tests (Wilcoxon, Friedman analysis of variance) were applied. VEGF increased significantly from pre- to post-exercise with hypoxia and hypoxia/hyperoxia. MMP-2 increased significantly in all experimental runs, while MMP-9 only increased significantly with hypoxia and hypoxia/hyperoxia. Endostatin increased significantly with normoxia and hypoxia. However, the magnitude of changes did not differ significantly between conditions. Capillary blood lactate was significantly lower following cycling with hypoxia/hyperoxia than with hypoxia alone. Although differences in subjective ratings of perceived exertion failed significance, 7 subjects were less exerted with hypoxia/hyperoxia than with hypoxia. Submaximal cycling with hypoxia or alternating hypoxia/hyperoxia may induce a more reliable up-regulation of pro-angiogenic regulators compared with normoxia, while hypoxia/hyperoxia may be better tolerated than hypoxia alone.

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].…”

“…The study by Zebrowska et al [29] showed that shorttime hypoxia (FiO₂ = 15.1 %) combined with graded exercise allowed more effective glycaemia control in T1D patients when compared with the exercise in normoxia. Submaximal exercise with hypoxia (FiO₂ = 14.0 %) may induce up-regulation of serum pro-angiogenic regulators compared to normoxia in T2D [23].…”

Oxygen Supplementation Ameliorates Tibial Development via Stimulating Vascularization in Tibetan Chickens at High Altitudes

“…Brinkmann et al . indicated that alternating hypoxia/hyperoxia may induce a more reliable pro-angiogenic regulators up-regulation compared with normoxia 11 . Furthermore, several studies have been reported that high oxygen concentrations can modulate mRNA expression of several genes and related protein secretion including hypoxia inducible factor (HIF)-1α (a master oxygen sensitive transcriptional regulator), vascular endothelial growth factor-A (VEGFA), and interleukin (IL)-8 15 , 19 - 21 .…”

“…Numerous studies have been found that O 2 supplementation as a treatment has some beneficial effects for several diseases, such as chronic cardiopulmonary disease, diabetes and ischemia wounds 8 - 11 . Although increased O 2 supply has already been demonstrated that it has beneficial effects including improve action on tissue oxygenation via increased the amount of dissolved O 2 in blood, promote angiogenesis and improve wound healing 12 , 13 .…”

“…Furthermore, several studies have been reported that high oxygen concentrations can modulate mRNA expression of several genes and related protein secretion including hypoxia inducible factor (HIF)-1α (a master oxygen sensitive transcriptional regulator), vascular endothelial growth factor-A (VEGFA), and interleukin (IL)-8 15 , 19 - 21 . Particularly VEGFA, VEGF receptor-1 (VEGFR1/Flt-1) and VEGFR2 (KDR/Flk-1) are the critical pro-angiogenic factor for vascular formation 11 , 22 , 23 . Kendall et al .…”