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Chronic intermittent hypoxia leads to insulin resistance and impaired glucose tolerance through dysregulation of adipokines in non-obese rats

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Abstract

Background and objectives

The aim of this study was to determine whether chronic intermittent hypoxia (CIH) could affect the secretion of adipokines, such as resistin, leptin, and adiponectin, in non-obese rats and to investigate the potential mechanisms.

Methods

An established rodent model of CIH was utilized, in which rats were exposed to varying oxygen levels (7–21 %) respectively over a period of 5 weeks. The area under the curve (AUCG) and the insulin resistance index (homeostasis model of assessment for insulin resistance index, HOMA-IR) were calculated. The levels of several secretory factors in the blood were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expression in adipose tissues was measured by reverse transcription-polymerase chain reaction (RT-PCR).

Results

Glucose tolerance and the levels of adiponectin in non-obese rats were decreased in the CIH group both in the serum and adipose tissue compared with the controls, while the insulin resistance index and the levels of resistin and leptin were increased. Moreover, the expressions of hypoxia inducible factor-1α and lactate dehydrogenase A were significantly higher in chronic intermittent hypoxia rats than in control rats, suggesting the presence of adipose tissue hypoxia.

Conclusions

These results show that CIH leads to insulin resistance (IR) and impaired glucose tolerance (IGT) in a non-obese rodent model of obstructive sleep apnea-hypopnea syndrome, and these effects may be due to the dysregulation of adiponectin, resistin, and leptin.

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Acknowledgments

This study was funded by Shanghai Committee of Science and Technology (No. 13430720500), Shanghai Leading Academic Discipline Project (No. B115), and National Natural Science Foundation of China (No. 81472175).

Conflict of interest

There is no financial or personal relationship with other people or organizations that could inappropriately influence this work.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The manuscript does not contain clinical studies or patient data. All animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1975 Declaration of Helsinki, as revised in 1983.

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    Authors and Affiliations

    1. Department of Respiratory Medicine, Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China

      Cuiping Fu, Fen Zhu, Zilong Liu, Wenjing Li, Hong Jiang & Shanqun Li

    2. Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China

      Liyan Jiang

    3. Division of Endocrinology, Hua Shan Hospital, Fudan University, Shanghai, China

      Hongying Ye

    4. Stanford University Sleep Clinic and Center for Human Sleep Research, Redwood City, CA, USA

      Clete A. Kushida

    5. Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Fenglin Road 180, Xuhui District, Shanghai, 200032, People’s Republic of China

      Shanqun Li

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    1. Cuiping Fu
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    Correspondence to Hongying Ye, Clete A. Kushida or Shanqun Li.

    Additional information

    Cuiping Fu and Liyan Jiang contributed equally to this work.

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    Fu, C., Jiang, L., Zhu, F. et al. Chronic intermittent hypoxia leads to insulin resistance and impaired glucose tolerance through dysregulation of adipokines in non-obese rats. Sleep Breath 19, 1467–1473 (2015). https://doi.org/10.1007/s11325-015-1144-8

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    • DOI: https://doi.org/10.1007/s11325-015-1144-8

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