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Decreased Sestrin levels in patients with type 2 diabetes and dyslipidemia and their association with the severity of atherogenic index

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Abstract

Purpose

We earlier reported that Sestrin2 regulates monocyte activation and atherogenic events through AMPK-mTOR nexus under high-glucose and dyslipidemic conditions. However, the statuses of Sestrins in diabetes and dyslipidemia are not known. We report here on the status of Sestrins and their association with diabetic dyslipidemia and atherosclerosis.

Methods

Individuals with normal glucose tolerance (NGT) (n = 46), dyslipidemia (n = 42), and patients with Type 2 diabetes with (n = 41) and without dyslipidemia (n = 40) were recruited from a tertiary diabetes centre, Chennai, India to study the mRNA expression levels of Sestrins (1, 2, and 3) in monocytes by RT-qPCR. Serum levels of Sestrins were measured using ELISA. Atherogenic index of plasma was calculated as log (triglyceride/HDL).

Results

mRNA expressions of Sestrin1 and Sestrin3 were significantly reduced in monocytes under dyslipidemic conditions but not in diabetes condition. Interestingly, Sestrin2 mRNA expression was significantly reduced in all disease conditions including dyslipidemia, and diabetes with and without dyslipidemia. Sestrin2 mRNA levels were negatively correlated with glycemic and lipid parameters and plasma atherogenic index. Furthermore, circulatory Sestrin2 was also found to be significantly decreased in dyslipidemia (415.2 ± 44.7 pg/ml), diabetes (375 ± 45 pg/ml), and diabetes with dyslipidemia (319.2 ± 26.3 pg/ml) compared to NGT (706.3 ± 77 pg/ml) and negatively correlated with glycemic, lipid parameters, and plasma atherogenic index.

Conclusion

We report for the first time that Sestrins levels are significantly decreased in diabetes and dyslipidemic conditions. More strikingly, Sestrin2 had a strong association with atherogenic risk factors and severity of atherogenic index and we suggest that Sestrin2 may be used as a biomarker for assessing atherogenesis.

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Acknowledgements

The study is supported by a research grant from the Department of Biotechnology (DBT, Ref.No. BT/PR6550/GBD/27/451/2012) and Mr. Saravanakumar Sundararajan acknowledges ICMR for the fellowship (2017-2773/CMB-BMS)

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Authors and Affiliations

  1. Department of Vascular Biology, Madras Diabetes Research Foundation and ICMR Centre for Advanced Research On Diabetes, Chennai, India

    S. Sundararajan, I. Jayachandran, B. Venkatesan & N. Manickam

  2. Clinical Epidemiology, Madras Diabetes Research Foundation, Chennai, India

    S. C. Subramanian

  3. Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialities Centre, Who Collaborating Centre for Non-Communicable Diseases Prevention and Control, Chennai, India

    R. M. Anjana & V. Mohan

  4. Department of Cell and Molecular Biology, Madras Diabetes Research Foundation, Chennai, India

    M. Balasubramanyam

  5. Science and Engineering Research Board, New Delhi, India

    B. Venkatesan

Authors
  1. S. Sundararajan
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  2. I. Jayachandran
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  3. S. C. Subramanian
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  4. R. M. Anjana
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  5. M. Balasubramanyam
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  6. V. Mohan
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  7. B. Venkatesan
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  8. N. Manickam
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Contributions

NM and BV conceptualized and designed the study; drafted the manuscript; reviewed and revised the manuscript. SS carried out the experiments and drafted the initial manuscript. SS, IJ, and SCS were involved in the subject recruitment and data collection. NM, SS, and IJ were involved in sample and data analysis. RMA, MB, and VM were involved in the critical reviewing of data analysis and manuscript writing.

Corresponding authors

Correspondence to B. Venkatesan or N. Manickam.

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The authors declare that there is no duality of interest associated with this manuscript.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all patients for being included in the study.

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Sundararajan, S., Jayachandran, I., Subramanian, S.C. et al. Decreased Sestrin levels in patients with type 2 diabetes and dyslipidemia and their association with the severity of atherogenic index. J Endocrinol Invest 44, 1395–1405 (2021). https://doi.org/10.1007/s40618-020-01429-9

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  • DOI: https://doi.org/10.1007/s40618-020-01429-9

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