Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2012; 58(5): 56-64


Continuous adaptation of ratsto hypobaric hypoxia preventsstressor hyperglycemia andoptimizes mitochondrialrespiration under acute hypoxia

V.I. Portnichenko, V.I. Nosar, A.M. Sydorenko,A.G. Portnychenko, I.M. Mankovska

    International Centre for Astronomical, Medical and EcologicalResearch NAS of Ukraine;O.O.Bogomoletz Institute of Physiology NAS of Ukraine,Kyiv.


Abstract

Oxygen consumption, glucose blood level and liver mi-tochondrial respiration were investigated in male Wistar rats permanently living in middle altitude (2100 m, Elbrus region). The animals were characterized by reduced body oxygen consumption and blood glucose level, as well as by intensifed utilization of NAD-dependent substrates in mitochondrial respiratory chain with increasing indices of ADP-stimulated respiration in comparison with plains rats. As a result of adaptive rebuilding of oxidative metabolism in rats – inhabitants of midlands, the nature and severity of metabolic responses to acute hypoxia were also changed. After lifting in barochamber to a “height’ of 5600 m during 3 hours, plains rats transiently demonstrated hypometabolic and hyperglycemic reactions. A rapid adaptation of mitochondrial function occurred due to increase in the rate of FAD-dependent substrate oxidation accompanied by a decrease in the effectiveness of phosphorylation. In midland rats, by contrast, hypoglycemic reaction was developed, and further reduction of aerobic metabolism was limited. Rapid adaptation of mitochondrial function to acute hypoxia in those rats was more intense than in the plains animals. This was achieved by a signifcant increase in the rate of NAD-dependent substrate oxidation, especially lipids, and an improved effciency of mitochondrial respiration and an increased economy of oxygen utilization.

Keywords: high altitude hypoxia, acute hypoxia, hyperglycemia,hypoglycemia, hypometabolism, mitochondrial respiration,carbohydrate metabolism, lipid metabolism.

References

  1. Акматкулова Д.А. Уровень гликемии и результаты пробы на толерантность к глюкозе у здоровых взро­слых жителей высокогорья Памира (2400–4000 м) // Сахарный диабет в условиях климата Киргизии / Сб. научн. тр. КГМИ. – Фрунзе, 1975. – Т. 105. – С.17–23.
  2. Западнюк И.П., Западнюк В.И., Захария Е.А., Запад-нюк Б.В. Лабораторные животные. Разведение, содержание, использование в эксперименте. – К.: Вища школа, 1983. – 384 с.
  3. Комро Дж. Г., Форстер Р. Э., Дюбуа А. Б., Бриско У. А., Карлсен Э. Легкие. Клиническая физиология и функциона льные пробы / Под ред. проф. Шика Л. – М ; Медгиз, 1961. – 196 с.
  4. Лебкова Н.П. Трансформация липидов в гликоген в клетках животных и человека // Арх.патологии. – 1982. – №6. – C.68–76.
  5. Лебкова Н.П. Ультраструктурная организация мито­хондрий при гипоксии и ее регуляция // Гіпоксія: де­структивна та конструктивна дія. – 1998. – С. 117–118.
  6. Ленинджер А. Основы биохимии: В 3 т. – Т.2. – М.: Мир, 1985. –368 с.
  7. Лукьянова Л.Д. Современные проблемы гипоксии // Вестн. РАМН. – 2000. – №9. – С. 3–12.
  8. Портніченко В.І., Портниченко А.Г., Сурова О.В. Гі­поглікемія та індукція генів у міокарді і легенях щурів при гіпобаричній гіпоксії // Здобутки клін. і експерим. медицини. – 2009. – №2. – С. 65–68.
  9. 9. Ambrosini G., Nath A.K., Sierra-Honigmann M.R., Flores-Riveros J. Transcriptional activation of the hu­man leptin gene in response to hypoxia. Involvement of hypoxia-inducible factor 1 // J. Biol. Chem. – 2002. – 277. – P.34601–34609.
  10. 10. Chance B., Williams G.R. Respiratory enzymes in oxida-tive phosphorylation. Kinetics of oxygen utilization // Ibid. – 1955. – 217. – P. 383–393.
  11. Daneshrad Z., Garcia-Riera M.P., Verdys M., Rossi A. Dif­ferential responses to chronic hypoxia and dietary restriction of aerobic capacity and enzyme levels in the rat myocardium // Mol. Cell. Biochem. – 2000. – 210. – P.159–166.
  12. Epstein A.C., Gleadle J.M., McNeill L.A., Hewitson K.S., O’Rourke J., Mole D.R., Mukherji M., Metzen E., Wilson M.I., Dhanda A., Tian Y.M., Masson N., Hamilton D.L., Jaakkola P. , Barstead R., Hodgkin J., Maxwell P.H., Pugh C.W., Schofeld C.J., Ratcliffe P.J. C. elegans EGL-9 and mammalian homologs defne a family of dioxygenases that regulate HIF by prolyl hydroxylation // Cell. – 2001. – 107. – P . 43–54.
  13. Estabrook R.W. Mitochondrial respiratory control and the polarographic measurement of ADP: O Ratios // Metod Enzymol. – 1967. – 10. – P. 41–47.
  14. Gnaiger E., Renner K. High-Resolution Respirometry with Cultured Cells: A Demonstration Experiment // Mitochon-drial pathways and respiratory control / Ed. E.Chaiger. – Innsbruck. OROBOROS MiPNet Publ., 2007. – P. 62–68.
  15. Ke Chen, Yuan-Hai Li, Si-Qi Xu, Sheng-Hong Hu, Lei Zhang. Protective effects of peroxisome proliferator-Activated receptor-a agonist, Wy14643, on hypoxia/ reoxygenation injury in primary rat hepatocytes // PPAR Res. – 2012. – Р. 547980.
  16. Kennedy S.L., StanleyW.C., Panchal A.R., Mazzeo R.S. Alterations in enzymes involved in fat metabolism after acute and chronic altitude exposure // J. Appl. Physiol. – 2001. – 90. – Р. 17–22.
  17. Kondrashova M.N., Fedotcheva N.I., Saakyan I.R. Pres­ervation of native properties of mitochondria in rat liver homogenate // Mitochondrion. – 2001. – №1. – P.249–267.
  18. Krishnan J., Suter M., Windak R., Krebs T., Felley A., Montessuit C., Tokarska-Schlattner M., Aasum E., Bogdanova A., Perriard E., Perriard J.C., Larsen T., Pedrazzini T., Krek W. Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy // Cell Metab. – 2009. – 9. – P. 512–524.
  19. 19. Larsen J.J., Hansen J.M., Olsen N.V., Galbo H., Dela F. The effect of altitude hypoxia on glucose homeostasis in men // J. Physiol. – 1997. – 504. – P.241–249.
  20. 20. Miranda M., Escote X., Ceperuelo-Mallafre V., Megia A., Caubet E., Naf S., Gomez J. M., Gonzalez-Clemente J. M., Vicente V., Vendrell J. Relation between human LPIN1, hypoxia and endoplasmic reticulum stress genes in subcutaneous and visceral adipose tissue // Int. J. Obes. (London). – 2010. – 34. – P.679–686.
  21. Philp A., Macdonald A.L.,Watt P.W. Lactate – a signal coordinating cell and systemic function // J. Exp. Biol. – 2006. – 208. – P. 4561–4575.
  22. Sharma S., Taegtmeyer H., Adrogue J., Razeghi P., Sen S., Ngumbela K., Essop M.F. Dynamic changes of gene expression in hypoxia-induced right ventricular hypertro­phy // Amer. J. Physiol. Heart. Circulat. Physiol. – 2004. – 286. – P.1185–1192.
  23. Shen G.M., Zhao Y.Z., Chen M.T., Zhang F.L., Liu X.L., Wang Y., Liu C.Z., Yu J., Zhang J.W. Hypoxia inducible factor 1 (HIF1) promotes LDL and VLDL uptake through inducing VLDLR under hypoxia // Biochem. J. Immed. Public. – 2011. – October.
  24. Shen G.M., Zhang F.L., Liu X.L., Zhang J.W. Hypoxia-inducible factor 1-mediated regulation of PPP1R3C promotes glycogen accumulation in human MCF-7 cells under hypoxia // FEBS Lett. – 2010. – 584. – P.4366-4372.
  25. Van Liere E.J., Stickney J.C., Hypoxia. Chiсago; London: Univ. of Chiсago Press. –1963. – 367 p.
  26. Wada Y., Sugiyama A., Yamamoto T., Naito M., Noguchi N., Yokoyama S., Tsujita M., Kawabe Y., Kobayashi M., Izumi A., Kohro T., Tanaka T., Taniguchi H., Koyama H., Hirano K., Yamashita S., Matsuzawa Y., Niki E., Hamak-ubo T., Kodama T. Lipid accumulation in smooth muscle cells under LDL loading is independent of LDL receptor pathway and enhanced by hypoxic conditions // Arterios. Thromb. Vascular Biol. – 2002. – 22. – P.1712–1719.

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.