Gustavo Dias Ferreira1, Ariane Germeyer2, Amanda de Barros Machado1, Tadeu Ludwig do Nascimento1, Thomas Strowitzki2, Ilma Simoni Brum1, Helena von Eye Corleta3, Edison Capp4. 1. Laboratório de Biologia Molecular Endócrina e Tumoral, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil; Laboratório de Ginecologia e Obstetrícia Molecular, Centro de Pesquisa Experimental, Departamento de Ginecologia e Obstetrícia, Hospital de Clínicas de Porto Alegre, UFRGS, Brazil. 2. Department of Gynecological Endocrinology and Reproductive Medicine, University Hospital Heidelberg, Heidelberg, Germany. 3. Laboratório de Biologia Molecular Endócrina e Tumoral, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil; Laboratório de Ginecologia e Obstetrícia Molecular, Centro de Pesquisa Experimental, Departamento de Ginecologia e Obstetrícia, Hospital de Clínicas de Porto Alegre, UFRGS, Brazil; Serviço de Ginecologia e Obstetrícia, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, RS CEP 90035-003, Brazil. 4. Laboratório de Biologia Molecular Endócrina e Tumoral, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil; Laboratório de Ginecologia e Obstetrícia Molecular, Centro de Pesquisa Experimental, Departamento de Ginecologia e Obstetrícia, Hospital de Clínicas de Porto Alegre, UFRGS, Brazil; Department of Gynecological Endocrinology and Reproductive Medicine, University Hospital Heidelberg, Heidelberg, Germany; Serviço de Ginecologia e Obstetrícia, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, RS CEP 90035-003, Brazil. Electronic address: edcapp@ufrgs.br.
Abstract
OBJECTIVE: To assess the effect of metformin on expression of Akt, ERK, PI3K and GLUT4, proteins associated with the growth factor signaling cascade, in human endometrial stromal cells after stimulation with androgen and insulin. STUDY DESIGN: Primary culture of endometrial stromal cells were stimulated in different groups with estrogen, progesterone, androgen and insulin and treated with metformin for 10min, 24h and 48h. After 14 days, proteins were extracted for Western blot analysis. RESULTS: PI3K and GLUT4 expression were increased in the insulin-treated group and further attenuated when metformin was added. The ERK protein was not affected, whereas the Akt phosphorylation was significantly decreased by the action of metformin. CONCLUSION: Metformin affects human endometrial stromal cells by acting on proteins related to growth factors, usually increasing their expression when combined with insulin. Akt phosphorylation was inhibited by metformin, possibly due to its anti-proliferative action.
OBJECTIVE: To assess the effect of metformin on expression of Akt, ERK, PI3K and GLUT4, proteins associated with the growth factor signaling cascade, in human endometrial stromal cells after stimulation with androgen and insulin. STUDY DESIGN: Primary culture of endometrial stromal cells were stimulated in different groups with estrogen, progesterone, androgen and insulin and treated with metformin for 10min, 24h and 48h. After 14 days, proteins were extracted for Western blot analysis. RESULTS: PI3K and GLUT4 expression were increased in the insulin-treated group and further attenuated when metformin was added. The ERK protein was not affected, whereas the Akt phosphorylation was significantly decreased by the action of metformin. CONCLUSION: Metformin affects human endometrial stromal cells by acting on proteins related to growth factors, usually increasing their expression when combined with insulin. Akt phosphorylation was inhibited by metformin, possibly due to its anti-proliferative action.
Authors: Jiten Patel; Jose R Torrealba; Emilio D Poggio; Jack Bebiak; Charles E Alpers; Stephanie M Grewenow; Robert D Toto; Michael T Eadon Journal: Clin J Am Soc Nephrol Date: 2021-12-15 Impact factor: 10.614
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Authors: Flavio R Palma; Bianca A Ratti; Veronica Paviani; Diego R Coelho; Rodrigo Miguel; Jeanne M Danes; Sofia V Zaichik; Andre L de Abreu; Sueli O Silva; Yiliang Chen; Roy L Silverstein; Uppal Karan; Dean P Jones; Marcelo G Bonini Journal: Oncogene Date: 2021-07-21 Impact factor: 9.867