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?

• Published in: Endocrine Vol. 75; no. 3; pp. 804 - 813
• Main Authors: Jensterle, Mojca, Kravos, Nika Aleksandra, Dolžan, Vita, Goričar, Katja, Herman, Rok, Rizzo, Manfredi, Janež, Andrej
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-03-2022; Springer Nature B.V
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Biopsy; Body fat; Diabetes; Endocrinology; Female; Gene expression; Glucose Transport Proteins, Facilitative - metabolism; Glucose transporter; Humanities and Social Sciences; Humans; Insulin; Internal Medicine; Medicine; Medicine & Public Health; Metformin; Metformin - pharmacology; Metformin - therapeutic use; multidisciplinary; Original Article; Polycystic Ovary Syndrome - metabolism; RNA, Messenger - metabolism; Science; Subcutaneous Fat - metabolism; PCOS; Adipose tissue; Metformin; GLUT-4 mRNA
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-021-02934-4

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.