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A possible role for AMP-activated protein kinase activated by metformin and AICAR in human granulosa cells

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are generally insulin- resistant and are consequently often treated with metformin. We investigated the effect of metformin and AICAR on the AMP-activated protein kinase (AMPK) pathway. METHODS: We evaluated the effects of 5-amino-imidazole-4-c...

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Detalles Bibliográficos
Autores principales: Kai, Yufuko, Kawano, Yasushi, Yamamoto, Hanae, Narahara, Hisashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397678/
https://www.ncbi.nlm.nih.gov/pubmed/25889494
http://dx.doi.org/10.1186/s12958-015-0023-2
Descripción
Sumario:BACKGROUND: Women with polycystic ovary syndrome (PCOS) are generally insulin- resistant and are consequently often treated with metformin. We investigated the effect of metformin and AICAR on the AMP-activated protein kinase (AMPK) pathway. METHODS: We evaluated the effects of 5-amino-imidazole-4-carboxyamide-1- beta-D-ribofuranoside (AICAR) and metformin on tumor necrosis factor (TNF)-alpha- stimulated chemokine production in human granulosa cells. The phosphorylations of AMPK, I-kappaB, 4E-BP-1, p70S6K were analyzed by western immunoblotting. RESULTS: AICAR and metformin markedly reduced the IL-8 and GROalpha production induced by TNF-alpha. AICAR and metformin also reduced the TNF-alpha-induced phosphorylation of I-kappaB. The phosphorylations of I-kappaB, 4EBP-1, p70S6K were inhibited via an AMPK-dependent signal transduction. CONCLUSIONS: These results suggest that metformin promotes granulosa cell function by reducing a TNF-alpha- and chemokine-mediated inflammatory reaction through an AMPK-dependent pathway. These finding may have implications for metformin’s actions during the treatment of PCOS with metformin.