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Glucose transporter 4 mRNA expression in subcutaneous adipose tissue of women with PCOS remains unchanged despite metformin withdrawal: is there a cellular metabolic treatment legacy effect?

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Abstract

Purpose

Metformin induces GLUT-4 mRNA expression in insulin target tissues in PCOS. It is unclear how long this impact is sustained after withdrawal of metformin. We aimed to compare the effect of metformin withdrawal on GLUT-4 mRNA expression in subcutaneous adipose tissue after prior short (ST, 1 year, N = 11) and long term (LT, at least 3 years, N = 13) treatment in obese PCOS women.

Methods

At baseline and 6 months after withdrawal, biopsy of subcutaneous adipose tissue followed by quantitative PCR analysis was performed to determine GLUT-4 mRNA expression.

Results

We found no time/effect differences in GLUT-4 mRNA expression in ST (2-dCt at baseline 0.42 (0.16–0.48) vs 2-dCt after 6 months 0.31 (0.22–0.56), p = 0.594) and no time/effect difference in LT group (2-dCt at baseline 0.24 (0.14–0.39) vs 2-dCt after 6 months 0.25 (0.20–0.38), p = 0.382). There was also no difference in GLUT-4 mRNA expression between both groups at baseline and after 6 months.

Conclusions

In summary, 6 months after metformin withdrawal, GLUT-4 mRNA expression in subcutaneous adipose tissue remained stable, regardless of the prior treatment duration.

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Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the study participants. We appreciate the assistance of Mirela Ozura, Elizabeta Stepanovic and Melita Dolenc, RNs. We wish to acknowledge Mrs. Savica Soldat, B.S., for her expert technical assistance with RNA isolation and assist. Tanja Blagus, B.S. for gene expression analyses.

Funding

This research was funded by Slovenian Research Agency, grant numbers #P3-0298 and P1-0170.

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Authors and Affiliations

  1. Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, Ljubljana, 1000, Slovenia

    Mojca Jensterle, Nika Aleksandra Kravos, Rok Herman & Andrej Janež

  2. Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, 1000, Slovenia

    Mojca Jensterle, Nika Aleksandra Kravos, Rok Herman & Andrej Janež

  3. Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, 1000, Slovenia

    Vita Dolžan & Katja Goričar

  4. Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Palermo, 90133, Italy

    Manfredi Rizzo

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Conceptualization: A.J. and M.J.; methodology: K.G., M.J., V.D.; formal analysis: K.G., M.J., N.A.K.; writing—original draft preparation: M.J., N.A.K., R.H.; writing—review and editing: A.J., M.R., V.D. All authors have read and agreed to the published version of the paper.

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Correspondence to Andrej Janež.

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Conflict of interest

The authors declare that the current research was conducted independently. Mojca Jensterle has given lectures, received honoraria and participated in conferences, advisory boards sponsored by pharmaceutical companies including Amgen, Pfeizer, Novo Nordisk, Novartis. Andrej Janez has given lectures, received honoraria and research support, and participated on Speakers Bureaus, advisory boards and clinical trials sponsored by pharmaceutical companies including AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Medtronic and Sanofi. Manfredi Rizzo is a full-time Professor of Internal Medicine at the University of Palermo, Italy, and currently Medical Director in Novo Nordisk Eastern Europe; he has given lectures, received honoraria and research support, and participated in conferences, advisory boards and clinical trials sponsored by many pharmaceutical companies including Amgen, AstraZeneca, Boehringer Ingelheim, Kowa, Eli Lilly, Meda, Mylan, Merck Sharp & Dohme, Novo Nordisk, Novartis, Roche Diagnostics, Sanofi and Servier. None of the above had any role in this article, which has been written independently, without any financial or professional help, and reflects only the opinion of the authors, without any role of the industry.

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All subjects were informed of the study aims and provided written consent to participate in a study and have their data published in a journal article.

Ethical approval

The study was conducted according to the guidelines of the Declaration of Helsinki and its later amendment and was approved by the National Ethical Committee (protocol code 0120101/2018/18).

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Jensterle, M., Kravos, N.A., Dolžan, V. et al. Glucose transporter 4 mRNA expression in subcutaneous adipose tissue of women with PCOS remains unchanged despite metformin withdrawal: is there a cellular metabolic treatment legacy effect?. Endocrine 75, 804–813 (2022). https://doi.org/10.1007/s12020-021-02934-4

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