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Endocrine Abstracts (2022) 81 P382 | DOI: 10.1530/endoabs.81.P382

ECE2022 Poster Presentations Endocrine-Related Cancer (41 abstracts)

Effect of metformin on the activity of the mTORC1 complex in patients with type 2 diabetes

Tamara Vatseba 1 , Liubov Sokolova 2 , Volodymyr Pushkarev 2 , Viktor Pushkarev 2 , Olena Kovzun 2 & Mykola Tronko 2


1Ivano-Frankivsk National Medical University, Endocrinology, Ivano-Frankivsk, Ukraine; 2V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine


Introduction: The increased risk of cancer in patients with diabetes mellitus (DM) creates an interest in finding mechanisms of the possible association of antidiabetic drugs and carcinogenesis. Metformin has the most documented evidence of pleiotropic oncoprotective effects, including increased stabilization of tumour suppressor p53, inhibition of NF-κB activation, slowing of the cell cycle and inhibition of mitosis due to decreased expression of cyclin D and cyclin E, as well as the positive effect on intestinal microbiota. The study of the drug’s ability to affect the activation of insulin signalling PI3K/Akt/mTOR, which is involved in the regulation of carcinogenesis and metabolism, continues. The aim of the study was to compare the activity of PI3K/Akt/mTOR in patients with type 2 diabetes on metformin monotherapy and other antidiabetic regimens.

Methods: To assess the activation of the PI3K/Akt/mTOR pathway in patients with type 2 diabetes by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells, the content of natural inhibitor of mTORC1 - phosphorylated PRAS40 and the content of phosphorylated protein kinase p70S6K1 were determined. The amounts of phospho-PRAS40 (P-Thr246) and phospho-p70S6K1 (P-Thr389) were determined using a microplate reader of “Bio-tek Instruments” company (USA) at a wavelength of 450 nm with the diagnostic ELISA kits (KHO0421, 85-86053 respectively (Invitrogen, USA)).

Results: Significantly lower phospho-PRAS40 levels in patients with type 2 DM on metformin monotherapy compared with patients on combination therapy with sulfonylurea derivatives (SUD) and metformin (t=2.34;P<0.05); lower levels of phospho-p70S6K in patients on monotherapy with metformin in comparison to patients on combination therapy with SUD and metformin (t=4.13;P<0.05), combination therapy with SUD and insulin (t=3.76;P<0.05), combined therapy with SUD, metformin and DPP-4 inhibitors (t=4.0;P<0.05), on insulin monotherapy (t=3.85; P<0.05) were found. The decrease in the content of phospho-PRAS40 on metformin monotherapy can be explained by the ability of the drug to increase the interaction of PRAS40 with Raptor in the mTORC1 complex, which influences the phosphorylation activity of PRAS40. Decrease in the content of phospho-p70S6K (depending on the activity of the mTORC1 complex) may be explained by the ability of metformin to increase the level of AMPK, the negative regulator of mTORC1.

Conclsion: The obtained results confirm the property of metformin to inhibit the activity of the mTORC1 complex.

Key words: metformin, type 2 diabetes mellitus, PI3K/Akt/mTOR, phospho-PRAS40, phospho-p70S6K.

Volume 81

European Congress of Endocrinology 2022

Milan, Italy
21 May 2022 - 24 May 2022

European Society of Endocrinology 

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