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Circulating TRB3 and GRP78 levels in type 2 diabetes patients: crosstalk between glucose homeostasis and endoplasmic reticulum stress

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Abstract

Purpose

Endoplasmic reticulum (ER) stress is implicated in the development of type 2 diabetes mellitus (T2DM) and insulin resistance. Tribbles homolog 3 (TRB3) is a pseudokinase upregulated by ER stress and hyperglycemia. Glucose-regulated protein 78 (GRP78) is an ER stress protein that is overexpressed under ER stress conditions. The current study aimed to investigate serum levels of TRB3 and GRP78, as an ER stress marker, in T2DM patients and their correlations with the metabolic profile.

Methods

Fifty-seven patients with type 2 diabetes and 23 healthy control subjects were evaluated for serum concentrations of TRB3, GRP78, and AGEs by enzyme-linked immunosorbent assay (ELISA). Fasting plasma glucose (FPG), HbA1c, lipid profile, TNF-α and insulin were also measured, and insulin resistance was calculated using a homeostasis model assessment of insulin resistance (HOMA-IR).

Results

Serum concentrations of TRB3, GRP78, AGEs, and TNF-α were significantly higher in T2DM patients compared to the healthy controls. Moreover, a statistically significant positive correlation was observed between plasma concentrations of TRB3 and FPG, HbA1c, HOMA-IR, and AGE. GRP78 levels were positively correlated with HbA1c and AGEs. There was also a positive correlation between GRP78 and TRB3. AGEs levels were positively correlated with the levels of FPG, HbA1c, HOMA-IR, and TNF-α.

Conclusion

The current findings suggest that TRB3 and GRP78 may contribute to the pathogenesis of T2DM and might be considered as a therapeutic targets for the treatment of this disease.

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Acknowledgements

This study was financially supported by a grant from Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences (grant number 1396-02-97-2170) and a grant from Iran University of Medical Science (grant number 33203).

Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

    M. Nourbakhsh, N. Heydari & H. Zarrinnahad

  2. Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    M. Nourbakhsh & S. Ezzati-Mobasser

  3. Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Iran University of Medical Sciences, 1449614535, Tehran, Iran

    R. Sharifi

  4. Hazrat Aliasghar Children’s Hospital, Iran University of Medical Sciences, Tehran, Iran

    M. Nourbakhsh

  5. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    S. Ezzati-Mobasser

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  1. M. Nourbakhsh
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Contributions

RS conducted and supervised the study design and contributed to the writing of the manuscript. M.N. conducted the study and edited the manuscript. NH and MN contributed to sample collection and preparation SEM and HZ performed the immunoassay experimental work. All authors read and approved the final manuscript.

Corresponding author

Correspondence to R. Sharifi.

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Conflict of interests

The authors declare that they have no competing interests.

Ethical approval

This study was performed in compliance with the ethical standards of the Declaration of Helsinki and Iran University of Medical Sciences. The study was approved by Ethics Committee of Iran University of Medical Sciences and Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences.

Informed consent

All subjects gave their written informed consent before participating in the study.

Data availability statement

The data and analysis of the present study are available from the corresponding author on reasonable request.

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Nourbakhsh, M., Sharifi, R., Heydari, N. et al. Circulating TRB3 and GRP78 levels in type 2 diabetes patients: crosstalk between glucose homeostasis and endoplasmic reticulum stress. J Endocrinol Invest 45, 649–655 (2022). https://doi.org/10.1007/s40618-021-01683-5

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  • DOI: https://doi.org/10.1007/s40618-021-01683-5

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