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Effect of metformin on the long non-coding RNA expression levels in type 2 diabetes: an in vitro and clinical trial study

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Abstract

Background

It has been suggested that the anti-hyperglycemic effect of metformin could be associated with its impact on long non-coding RNA (lncRNA) expression levels. Accordingly, in the current study, we evaluated the effect of metformin on the expression of H19, MEG3, MALAT1, and GAS5 in in vitro and in vivo situations.

Methods

The effect of hyperglycemia and metformin treatment on the lncRNAs expression level was evaluated in HepG2 cells. A total of 179 age- and sex-matched subjects, including 88 newly diagnosed patients with type 2 diabetes (T2D) and 91 healthy volunteers, were included in the case–control phase of the study. Moreover, 40 newly diagnosed patients participated in the study’s open-labeled non-controlled clinical trial phase. The expression levels of lncRNA in HepG2 cells and whole blood samples were determined using QRT-PCR.

Results

In vitro results showed that hyperglycemia induced H19 and MALAT1 and decreased GAS5 expression levels. Moreover, metformin decreased H19 and increased GAS5 expression in high glucose-treated cells. Case–control study findings revealed that the circulating levels of H19, MALAT1, and MEG3 were significantly elevated in T2D patients compared to the control subjects. Finally, results showed that the level of circulating H19 levels decreased while GAS5 increased in T2D patients after taking metformin for 2 months.

Conclusion

The results of the current study provided evidence that metformin could exert its effect in the treatment of T2D by altering the expression levels of H19 and GAS5.

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Data availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

Abbreviations

BMI:

Body mass index

FBG:

Fasting blood glucose

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GAS5:

Growth arrest-specific 5

H19:

H19 imprinted maternally expressed transcript

HbA1c:

Hemoglobin A1c

HDL‐C:

High‐density lipoprotein-cholesterol

HG:

High glucose

HOMA-IR:

Homeostatic model assessment of insulin resistance

LDL-C:

Low‐density lipoprotein-cholesterol

LncRNAs:

Long non-coding RNAs

MALAT1:

Metastasis-associated lung adenocarcinoma transcript 1

MEG3:

Maternally expressed 3

MET:

Metformin

miRNAs:

MicroRNAs

ncRNAs:

Non-coding RNAs

NG:

Normal glucose

T2D:

Type 2 diabetes

TC:

Total cholesterol

TG:

Triglycerides

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Acknowledgements

The authors greatly appreciate all volunteers for their participation in the study.

Funding

This work was financially supported by a Grant (960429) from the Deputy of Research, Yasuj University of Medical Sciences.

Author information

Authors and Affiliations

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

    Seyedeh Nasrin Parvar, Ali Mirzaei & Amir Hossein Doustimotlagh

  2. Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran

    Ali Mirzaei & Amir Hossein Doustimotlagh

  3. Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ali Zare

  4. Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran

    Shekoofeh Nikooei

  5. Internal Medicine Department of Yasuj Medical School, Yasuj, Iran

    Arash Arya

  6. Iran’s National Elites Foundation, Tehran, Iran

    Behnam Alipoor

  7. Department of Laboratory Sciences, Faculty of Paramedicine, Yasuj University of Medical Sciences, Yasuj, Iran

    Behnam Alipoor

Authors
  1. Seyedeh Nasrin Parvar
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  2. Ali Mirzaei
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Contributions

Behnam Alipoor planned the studies; Behnam Alipoor and Ali Mirzaei analyzed and interpreted all experiments; Seyedeh Nasrin Parvar, Ali Zare and Shekoofeh Nikooei conducted all the experiments. Behnam Alipoor and Amir Hossein Doustimotlagh wrote the manuscript; Arash Arya monitored the treatment of patients as internal medicine.

Corresponding author

Correspondence to Behnam Alipoor.

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Parvar, S.N., Mirzaei, A., Zare, A. et al. Effect of metformin on the long non-coding RNA expression levels in type 2 diabetes: an in vitro and clinical trial study. Pharmacol. Rep 75, 189–198 (2023). https://doi.org/10.1007/s43440-022-00427-3

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  • DOI: https://doi.org/10.1007/s43440-022-00427-3

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