Int J Sports Med 2017; 38(02): 92-98
DOI: 10.1055/s-0042-116823
Physiology & Biochemistry
© Georg Thieme Verlag KG Stuttgart · New York

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

Christian Brinkmann
1   Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany
,
Alexander Metten
1   Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany
,
Philipp Scriba
1   Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany
,
Christos V. M. Tagarakis
1   Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany
,
Patrick Wahl
2   Institute of Training Science and Sport Informatics, German Sport University Cologne, Cologne, Germany
,
Jo Latsch
3   Department of Preventive and Rehabilitative Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany
,
Klara Brixius
1   Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany
,
Wilhelm Bloch
1   Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany
› Author Affiliations
Further Information

Publication History



accepted after revision 05 September 2016

Publication Date:
09 January 2017 (online)

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%O2), hypoxia (≈14 vol%O2) and during alternating hypoxia/hyperoxia (≈14 vol%O2/≈30 vol%O2, 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.

Supplementary Material

 
  • References

  • 1 Berceli SA, Jiang Z, Klingman NV, Schultz GS, Ozaki CK. Early differential MMP-2 and -9 dynamics during flow-induced arterial and vein graft adaptations. J Surg Res 2006; 134: 327-334
  • 2 Breen EC, Johnson EC, Wagner H, Tseng HM, Sung LA, Wagner PD. Angiogenic growth factor mRNA responses in muscle to a single bout of exercise. J Appl Physiol 1996; 81: 355-361
  • 3 Brown MD, Hudlicka O. Modulation of physiological angiogenesis in skeletal muscle by mechanical forces: involvement of VEGF and metalloproteinases. Angiogenesis 2003; 6: 1-14
  • 4 Calbet JA, Boushel R, Rådegran G, Søndergaard H, Wagner PD, Saltin B. Determinants of maximal oxygen uptake in severe acute hypoxia. Am J Physiol 2003; 284: R291-R303
  • 5 Colville-Nash PR, Willoughby DA. Growth factors in angiogenesis: current interest and therapeutic potential. Mol Med Today 1997; 3: 14-23
  • 6 Dandona P, Aljada A, Mohanty P, Ghanim H, Bandyopadhyay A, Chaudhuri A. Insulin suppresses plasma concentration of vascular endothelial growth factor and matrix metalloproteinase-9. Diabetes Care 2003; 26: 3310-3314
  • 7 Deininger MH, Wybranietz WA, Graepler FT, Lauer UM, Meyermann R, Schluesener HJ. Endothelial endostatin release is induced by general cell stress and modulated by the nitric oxide/cGMP pathway. FASEB J 2003; 17: 1267-1276
  • 8 dela Paz NG, Walshe TE, Leach LL, Saint-Geniez M, D’Amore PA. Role of shear-stress-induced VEGF expression in endothelial cell survival. J Cell Sci 2012; 125: 831-843
  • 9 Ferrara N, Gerber H, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003; 9: 669-676
  • 10 Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 1996; 16: 4604-4613
  • 11 Fridén J, Lieber RL. Structural and mechanical basis of exercise-induced muscle injury. Med Sci Sports Exerc 1992; 24: 521-530
  • 12 Gu JW, Gadonski G, Wang J, Makey I, Adair TH. Exercise increases endostatin in circulation of healthy volunteers. BMC Physiol 2004; 4: 2
  • 13 Gustafsson T, Puntschart A, Kaijser L, Jansson E, Sundberg CJ. Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle. Am J Physiol 1992; 276: H679-H685
  • 14 Harriss DJ, Atkinson G. Ethical Standards in Sport and Exercise Science Research: 2016 Update. Int J Sports Med 2015; 36: 1121-1124
  • 15 Heinonen IH, Kemppainen J, Kaskinoro K, Peltonen JE, Borra R, Lindroos M, Oikonen V, Nuutila P, Knuuti J, Boushel R, Kalliokoski KK. Regulation of human skeletal muscle perfusion and its heterogeneity during exercise in moderate hypoxia. Am J Physiol 2010; 299: R72-R90
  • 16 Jensen L, Bangsbo J, Hellsten Y. Effect of high intensity training on capillarization and presence of angiogenic factors in human skeletal muscle. J Physiol 2004; 557: 571-582
  • 17 Koskinen SO, Höyhtyä M, Turpeenniemi-Hujanen T, Martikkala V, Mäkinen TT, Oksa J, Rintamäki H, Löfberg M, Somer H, Takala TE. Serum concentrations of collagen degrading enzymes and their inhibitors after downhill running. Scand J Med Sci Sports 2001; 11: 9-15
  • 18 Kraus RM, Stallings HW, Yeager RC, Gavin TP. Circulating plasma VEGF response to exercise in sedentary and endurance-trained men. J Appl Physiol 2004; 96: 1445-1450
  • 19 Lillioja S, Young AA, Culter CL, Ivy JL, Abbott WG, Zawadzki JK, Yki-Järvinen H, Christin L, Secomb TW, Bogardus C. Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man. J Clin Invest 1987; 80: 415-424
  • 20 Mackenzie R, Maxwell N, Castle P, Elliott B, Brickley G, Watt P. Intermittent exercise with and without hypoxia improves insulin sensitivity in individuals with type 2 diabetes. J Clin Endocrinol Metab 2012; 97: E546-E555
  • 21 Mårin P, Andersson B, Krotkiewski M, Björntorp P. Muscle fiber composition and capillary density in women and men with NIDDM. Diabetes Care 1994; 17: 382-386
  • 22 Martin A, Komada MR, Sane DC. Abnormal angiogenesis in diabetes mellitus. Med Res Rev 2003; 23: 117-145
  • 23 Moore DP, Weston AR, Hughes JM, Oakley CM, Cleland JG. Effects of increased inspired oxygen concentrations on exercise performance in chronic heart failure. Lancet 1992; 339: 850-853
  • 24 Niebauer J, Cooke JP. Cardiovascular effects of exercise: role of endothelial shear stress. J Am Coll Cardiol 1996; 28: 1652-1660
  • 25 O’Donnell DE, D’Arsigny C, Webb KA. Effects of hyperoxia on ventilatory limitation during exercise in advanced chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 163: 892-898
  • 26 Opitz D, Lenzen E, Schiffer T, Hermann R, Hellmich M, Bloch W, Brixius K, Brinkmann C. Endurance training alters skeletal muscle MCT contents in T2DM men. Int J Sports Med 2014; 35: 1065-1071
  • 27 Prior BM, Yang HT, Terjung RL. What makes vessels grow with exercise training?. J Appl Physiol 2004; 97: 1119-1128
  • 28 Shaw J, Sicree R, Zimmet P. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010 87: 4-14
  • 29 Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992; 359: 843-845
  • 30 Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C, White RD. Physical activity/exercise and type 2 diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29: 1433-1438
  • 31 Sponder M, Sepiol K, Lankisch S, Priglinger M, Kampf S, Litschauer B, Fritzer-Szekeres M, Strametz Juranek J. Endostatin and physical exercise in young female and male athletes and controls. Int J Sports Med 2014; 35: 1138-1142
  • 32 Suhr F, Brixius K, de Marées M, Bölck B, Kleinöder H, Achtzehn S, Bloch W, Mester J. Effects of short-term vibration and hypoxia during high-intensity cycling exercise on circulating levels of angiogenic regulators in humans. J Appl Physiol 2010; 103: 474-483
  • 33 Susta D, Dudnik E, Glazachev OS. A programme based on repeated hypoxia-hyperoxia exposure and light exercise enhances performance in athletes with overtraining syndrome: a pilot study. Clin Physiol Funct Imaging 2015; [Epub ahead of print] DOI: 10.1111/cpf.12296.
  • 34 van Dieren S, Beulens JW, van der Schouw YT, Grobbee DE, Neal B. The global burden of diabetes and its complications: an emerging pandemic. Eur J Cardiovasc Prev Rehabil 2010; 17 (Suppl. 01) 3-8
  • 35 Wahl P, Schmidt A, de Marées M, Achtzehn S, Bloch W, Mester J. Responses of angiogenic growth factors to exercise, to hypoxia and to exercise under hypoxic conditions. Int J Sports Med 2013; 34: 95-100
  • 36 Yamaguchi N, Anand-Apte B, Lee M, Sasaki T, Fukai N, Shapiro R, Que I, Lowik C, Timpl R, Olsen BR. Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding. EMBO J 1999; 18: 4414-4423