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Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients

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Abstract

Purpose

Intermittent hypoxia training/treatment (IHT) is an emerging therapeutic approach to alleviate chronic diseases, such as diabetes. The present study investigated the effects of IHT on blood leucocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and its relationship with the changes in blood insulin level.

Methods

Seven adult healthy volunteers and 11 prediabetic patients participated in this study. A 3-week course of IHT consisted of a 40-min session of 4 cycles of 5-min 12% O2 and 5-min room air breathing per day, 3 sessions per week for 3 weeks (i.e., total 9 sessions of IHT). Plasma insulin levels and leukocyte PDK-1 mRNA expression were determined at various time points either under fasting condition or following oral glucose tolerance test (OGTT). Correlation between the IHT-induced changes in PDK-1 mRNA and insulin or glucose levels in the same serological samples was analyzed.

Results

At pre-IHT baseline, PDK-1 mRNA expression was two times higher in prediabetes than control subjects. IHT resulted in significant augmentation in PDK-1 mRNA expression (> twofold) in prediabetes at the end of 3-week IHT and remained elevated 1 month after IHT, which was correlated with a significantly reduced insulin release and lower blood glucose after glucose loading with OGTT.

Conclusion

IHT can trigger beneficial effects in normalizing blood insulin levels in prediabetic patients under oral glucose load, which were closely correlated with an enhanced mRNA expression of PDK-1 in leukocytes. Further clinical trials are warranted to validate the utility of IHT as a non-invasive complementary therapy against diabetes-associated pathologies.

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Abbreviations

ANOVA:

Analysis of variance

GLUT:

Glucose transporter

HIF-1α:

Hypoxia inducible factor 1α

IHT:

Intermittent hypoxia training/treatment

INSR:

Insulin receptor

OGTT:

Oral glucose tolerance test

PDH:

Pyruvate dehydrogenase

PDK:

Pyruvate dehydrogenase kinase

PDK-1:

Pyruvate dehydrogenase kinase 1

R:

Correlation coefficient

SD:

Standard Deviation

TCA:

Tricarboxylic acid cycle

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Acknowledgements

The authors like to thank Valentina Chizhova for clinical examination of the subjects and Tetiana I. Drevytska for performing gene expression analysis.

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Authors and Affiliations

  1. Bogomoletz Institute of Physiology, Kiev, 01024, Ukraine

    Tetiana V. Serebrovska, Alla G. Portnychenko & Vladimir I. Portnichenko

  2. ICAMER, National Academy of Sciences of Ukraine, Kiev, 03680, Ukraine

    Alla G. Portnychenko & Vladimir I. Portnichenko

  3. Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7-020C, Richmond, VA, 23298, USA

    Lei Xi

  4. School of Sports Medicine and Health, Chengdu Sport University, Chengdu, 610041, China

    Lei Xi

  5. CELLGYM Technologies GmbH, 10623, Berlin, Germany

    Egor Egorov

  6. D.F. Chebotarev State Institute of Gerontology, Kiev, 04114, Ukraine

    Ivanna Antoniuk-Shcheglova, Svitlana Naskalova & Valeriy B. Shatylo

Authors
  1. Tetiana V. Serebrovska
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  2. Alla G. Portnychenko
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  3. Vladimir I. Portnichenko
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  4. Lei Xi
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  5. Egor Egorov
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  6. Ivanna Antoniuk-Shcheglova
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  7. Svitlana Naskalova
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  8. Valeriy B. Shatylo
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Contributions

All authors participated in the design and interpretation of the studies, data analysis, review, and final approval of the manuscript. TVS designed the study and wrote the manuscript. TVS, AGP, VIP, EE, IAS, SN, and VBS elaborated the study protocols and performed statistical analyses of the results. LX critically edited and final-assembled the manuscript. VBS provided the enrollment and clinical examination of the subjects as well as general research management.

Corresponding authors

Correspondence to Tetiana V. Serebrovska or Lei Xi.

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Conflict of interest

LX is a co-founder of Xiamen Innovo Medical Technology Co. Ltd., Xiamen, China and EE is an owner of CellGym Technologies GmbH, Berlin, Germany. All other authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article.

Ethical approval

The research protocols, patient health information and informed consent forms were approved by the Ethics Committee of Chebotarev Institute of Gerontology, Kiev, Ukraine. This human study was performed in accordance with the ethical standards according to the 1964 Declaration of Helsinki.

Informed consent

Informed consent was obtained from all individual participants included in this study.

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Communicated by Guido Ferretti.

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Serebrovska, T.V., Portnychenko, A.G., Portnichenko, V.I. et al. Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients. Eur J Appl Physiol 119, 813–823 (2019). https://doi.org/10.1007/s00421-019-04072-2

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