Published in:
Open Access
01-12-2015 | Research
A possible role for AMP-activated protein kinase activated by metformin and AICAR in human granulosa cells
Authors:
Yufuko Kai, Yasushi Kawano, Hanae Yamamoto, Hisashi Narahara
Published in:
Reproductive Biology and Endocrinology
|
Issue 1/2015
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Abstract
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.