SpringerLink
Log in

Intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats

  • Original Paper
  • Published:
Cell Stress and Chaperones Aims and scope

Abstract

Increasing studies have shown protective effects of intermittent hypoxia on brain injury and heart ischemia. However, the effect of intermittent hypoxia on blood glucose metabolism, especially in diabetic conditions, is rarely observed. The aim of this study was to investigate whether intermittent hypoxia influences blood glucose metabolism in type 1 diabetic rats. Streptozotocin-induced diabetic adult rats and age-matched control rats were treated with intermittent hypoxia (at an altitude of 3 km, 4 h per day for 3 weeks) or normoxia as control. Fasting blood glucose, body weight, plasma fructosamine, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), pancreas β-cell mass, and hepatic and soleus glycogen were measured. Compared with diabetic rats before treatment, the level of fasting blood glucose in diabetic rats after normoxic treatment was increased (19.88 ± 5.69 mmol/L vs. 14.79 ± 5.84 mmol/L, p < 0.05), while it was not different in diabetic rats after hypoxic treatment (13.14 ± 5.77 mmol/L vs. 14.79 ± 5.84 mmol/L, p > 0.05). Meanwhile, fasting blood glucose in diabetic rats after hypoxic treatment was also lower than that in diabetic rats after normoxic treatment (13.14 ± 5.77 mmol/L vs. 19.88 ± 5.69 mmol/L, p<0.05). Plasma fructosamine in diabetic rats receiving intermittent hypoxia was significantly lower than that in diabetic rats receiving normoxia (1.28 ± 0.11 vs. 1.39 ± 0.11, p < 0.05), while there were no significant changes in body weight, plasma insulin and β-cell mass. HOMA-IR in diabetic rats after hypoxic treatment was also lower compared with diabetic rats after normoxic treatment (3.48 ± 0.48 vs. 3.86 ± 0.42, p < 0.05). Moreover, intermittent hypoxia showed effect on the increase of soleus glycogen but not hepatic glycogen. We conclude that intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats and its regulation on muscular glycogenesis may play a role in the underlying mechanism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Anderson J, Honigman B (2011) The effect of altitude-induced hypoxia on heart disease: do acute, intermittent, and chronic exposures provide cardioprotection? High Alt Med Biol 12:45–55

    Article  PubMed  Google Scholar 

  • Azevedo JJ, Carey J, Pories W, Morris P, Dohm G (1995) Hypoxia stimulates glucose transport in insulin-resistant human skeletal muscle. Diabetes 44:695–698

    Article  CAS  PubMed  Google Scholar 

  • Brooks G et al (1991) Increased dependence on blood glucose after acclimatization to 4,300 m. J Appl Physiol 70:919–927

    Article  CAS  PubMed  Google Scholar 

  • Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625

    Article  CAS  PubMed  Google Scholar 

  • Burtscher M et al (2009) Intermittent hypoxia increases exercise tolerance in patients at risk for or with mild COPD. Respir Physiol Neurobiol 165:97–103

    Article  CAS  PubMed  Google Scholar 

  • Cartee G, Douen A, Ramlal T (1991) Stimulation of glucose transport in skeletal muscle by hypoxia. J Appl Physiol 70:1593–1600

    CAS  PubMed  Google Scholar 

  • DeFronzo R, Jacot E, Jequier E, Maeder E, Wahren J, Felber J (1981) The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 30:1000–1007

    Article  CAS  PubMed  Google Scholar 

  • Dill R, Chadan S, Li C, Parkhouse W (2001) Aging and glucose transporter plasticity in response to hypobaric hypoxia. Mech Ageing Dev 122:533–545

    Article  CAS  PubMed  Google Scholar 

  • Drager L, Jun J, Polotsky V (2010) Metabolic consequences of intermittent hypoxia: relevance to obstructive sleep apnea. Best Pract Res Clin Endocrinol Metab 24:843–851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finegood D, McArthur M, Kojwang D, Thomas M, Topp B, Leonard T, Buckingham R (2001) Beta-cell mass dynamics in Zucker diabetic fatty rats. Rosiglitazone prevents the rise in net cell death. Diabetes 50:1021–1029

    Article  CAS  PubMed  Google Scholar 

  • Galle A, Jones N (2012) The neuroprotective actions of hypoxic preconditioning and postconditioning in a neonatal rat model of hypoxic-ischemic brain injury. Brain Res. doi:10.1016/j.brainres.2012.12.026

    PubMed  Google Scholar 

  • Gamboa J, Garcia-Cazarin M, Andrade F (2011) Chronic hypoxia increases insulin-stimulated glucose uptake in mouse soleus muscle. Am J Physiol Regul Integr Comp Physiol 300:R85–R91

    Article  CAS  PubMed  Google Scholar 

  • Hamamoto Y et al (2001) Recovery of function and mass of endogenous beta-cells in streptozotocin-induced diabetic rats treated with islet transplantation. Biochem Biophys Res Commun 287:104–109

    Article  CAS  PubMed  Google Scholar 

  • Holmes B, Kurth-Kraczek E, Winder W (1999) Chronic activation of 5′-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle. J Appl Physiol 87:1990–1995

    CAS  PubMed  Google Scholar 

  • Klein R, Klein B, Moss S (1996) Relation of glycemic control to diabetic microvascular complications in diabetes mellitus. Ann Intern Med 124:90–96

    Article  CAS  PubMed  Google Scholar 

  • Lal C, Strange C, Bachman D (2012) Neurocognitive impairment in obstructive sleep apnea. Chest 141:1601–1610

    Article  PubMed  Google Scholar 

  • Lee E et al (2013) Time-dependent changes in glucose and insulin regulation during intermittent hypoxia and continuous hypoxia. Eur J Appl Physiol 113:467–478

    Article  CAS  PubMed  Google Scholar 

  • Lindgärde F, Ercilla M, Correa L, Ahrén B (2004) Body adiposity, insulin, and leptin in subgroups of Peruvian Amerindians. High Alt Med Biol 5:27–31

    Article  CAS  PubMed  Google Scholar 

  • Lippl F, Neubauer S, Schipfer S, Lichter N, Tufman A, Otto B, Fischer R (2010) Hypobaric hypoxia causes body weight reduction in obese subjects. Obesity (Silver Spring) 18:675–681

    Article  Google Scholar 

  • Liu J et al (2012) Intrauterine growth retardation increases the susceptibility of pigs to high-fat diet-induced mitochondrial dysfunction in skeletal muscle. PLoS One 7:e34835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mackenzie R, Maxwell N, Castle P, Brickley G, Watt P (2011) Acute hypoxia and exercise improve insulin sensitivity (S(I) (2*)) in individuals with type 2 diabetes. Diabetes Metab Res Rev 27:94–101

    Article  CAS  PubMed  Google Scholar 

  • Mackenzie R, Maxwell N, Castle P, Elliott B, Brickley G, Watt P (2012) Intermittent exercise with and without hypoxia improves insulin sensitivity in individuals with type 2 diabetes. J Clin Endocrinol Metab 97:E546–E555

    Article  CAS  PubMed  Google Scholar 

  • Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  CAS  PubMed  Google Scholar 

  • McCoy M, Proietto J, Hargreaves M (1996) Skeletal muscle GLUT-4 and postexercise muscle glycogen storage in humans. J Appl Physiol 80:411–415

    CAS  PubMed  Google Scholar 

  • Perseghin G et al (1996) Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects. N Engl J Med 335:1357–1362

    Article  CAS  PubMed  Google Scholar 

  • Pescador N et al (2010) Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1. PLoS One 5:e9644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prabhakar N, Semenza G (2012) Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2. Physiol Rev 92:967–1003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rafacho A, Gonçalves-Neto L, Ferreira F, Protzek A, Boschero A, Nunes E, Zoccal D (2013) Glucose homoeostasis in rats exposed to acute intermittent hypoxia. Acta Physiol (Oxf). doi:10.1111/apha.12118

    Google Scholar 

  • Roberts A, Reeves J, Butterfield G, Mazzeo R, Sutton J, Wolfel E, Brooks G (1996) Altitude and beta-blockade augment glucose utilization during submaximal exercise. J Appl Physiol 80:605–615

    CAS  PubMed  Google Scholar 

  • Roglic G et al (2005) The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care 28:2130

    Article  PubMed  Google Scholar 

  • Ruzzin J, Jensen J (2005) Contraction activates glucose uptake and glycogen synthase normally in muscles from dexamethasone-treated rats. Am J Physiol Endocrinol Metab 289:E241–E250

    Article  CAS  PubMed  Google Scholar 

  • **a Y, Warshaw J, Haddad G (1997) Effect of chronic hypoxia on glucose transporters in heart and skeletal muscle of immature and adult rats. Am J Physiol 273:1734–1741

    Google Scholar 

  • Youn J, Gulve E, Holloszy J (1991) Calcium stimulates glucose transport in skeletal muscle by a pathway independent of contraction. Am J Physiol 260:C555–C561

    CAS  PubMed  Google Scholar 

  • Young A, Evans W, Cymerman A, Pandolf K, Knapik J, Maher J (1982) Sparing effect of chronic high-altitude exposure on muscle glycogen utilization. J Appl Physiol 52:857–862

    CAS  PubMed  Google Scholar 

  • Yu S et al (2008) Hypoxic preconditioning up-regulates glucose transport activity and glucose transporter (GLUT1 and GLUT3) gene expression after acute anoxic exposure in the cultured rat hippocampal neurons and astrocytes. Brain Res 1211:22–29

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Lian B, Cui F (2008) Effect of FeSO4 treatment on glucose metabolism in diabetic rats. Biometals 21:685–691

    Article  CAS  PubMed  Google Scholar 

  • Zhou J et al (2009) Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Eur J Pharmacol 606:262–268

    Article  CAS  PubMed  Google Scholar 

  • Zhu L et al (2005) Neurogenesis in the adult rat brain after intermittent hypoxia. Brain Res 1055:1–6

    Article  CAS  PubMed  Google Scholar 

  • Zhu X et al (2010) Intermittent hypoxia promotes hippocampal neurogenesis and produces antidepressant-like effects in adult rats. J Neurosci 30:12653–12663

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Basic Research Programs of China (2011CB910800 and 2012CB518200).

Author information

Authors and Affiliations

  1. Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, No.27 Tai** Road, Bei**g, 100850, People’s Republic of China

    **aofei Chen, Tong Zhao, **n Huang, Liying Wu, Kuiwu Wu, Ming Fan & Lingling Zhu

  2. Department of Ophthalmology, Chinese PLA General Hospital, No. 28 Fuxing Road, Bei**g, 100853, People’s Republic of China

    **aofei Chen

Authors
  1. **aofei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tong Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. **n Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liying Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kuiwu Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ming Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lingling Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ming Fan or Lingling Zhu.

Ethics declarations

All treatments were approved by the Institutional Animal Care and Use Committee of the Academy of Military Medical Sciences.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, X., Zhao, T., Huang, X. et al. Intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats. Cell Stress and Chaperones 21, 515–522 (2016). https://doi.org/10.1007/s12192-016-0679-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12192-016-0679-3

Keywords

Search

Navigation