A potential mechanism of metformin-mediated regulation of glucose homeostasis: inhibition of Thioredoxin-interacting protein (Txnip) gene expression

Cellular Signalling
Tin Fan ChaiFa-Xing Yu

Abstract

Metformin (dimethylbiguanide) is widely used among diabetic patients to lower the blood sugar level. Although several mechanisms have been proposed, its mode of action in enhancing peripheral glucose uptake and inhibiting hepatic glucose production is not fully understood. Thioredoxin-interacting protein (Txnip) is known to play important roles in glucose metabolism by inhibiting cellular glucose uptake and metabolism and promoting hepatic gluconeogenesis. The expression of the gene encoding Txnip is regulated in a glucose dependent manner via the Mondo:MLX transcription factor complex. In the present study, we report that Txnip mRNA as well as protein expression in cultured cells is markedly reduced upon metformin administration. The binding of Mondo:MLX to the Txnip gene promoter is reduced, suggesting that the transcription of the Txnip gene is repressed by metformin. Moreover, we show that the effect of metformin on Txnip gene transcription is due to the inhibition of mitochondrial complex I and increased glycolysis, and is partially mediated by the AMP activated kinase (AMPK). These observations prompt us to propose that the novel action of metformin on the Txnip gene expression may contribute to its therapeutic effects in...Continue Reading

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Citations

Nov 7, 2015·Journal of Diabetes Investigation·Kyu Yeon Hur, Myung-Shik Lee
Mar 14, 2014·Redox Biology·Moshe Cohen-KutnerDaphne Atlas
Oct 20, 2018·International Journal of Molecular Sciences·Katarzyna E Skórzyńska-DziduszkoBożena Leszczyńska-Gorzelak
Jan 23, 2018·Current Opinion in Endocrinology, Diabetes, and Obesity·Lance Thielen, Anath Shalev
Jul 3, 2019·International Journal of Molecular Sciences·Hans-Juergen Schulten, Sherin Bakhashab
Mar 23, 2021·IScience·Benedicte NobletCatherine Postic
Apr 4, 2021·International Journal of Molecular Sciences·Naila QayyumSangdun Choi
Apr 10, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Xiaomin XieXiaoyan Zou
Jan 5, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Michela MassolloGianmario Sambuceti

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