The University of Southampton
University of Southampton Institutional Repository

Stimulation of lactate production in human granulosa cells by metformin and potential involvement of adenosine 5' monophosphate-activated protein kinase

Richardson, Malcolm C., Ingamells, Susan, Simonis, Chantal D., Cameron, Iain T., Sreekumar, Rajiv, Vijendren, Ananth, Sellahewa, Luckni and Coakley, Stephanie (2009) Stimulation of lactate production in human granulosa cells by metformin and potential involvement of adenosine 5' monophosphate-activated protein kinase Journal of Clinical Endocrinology and Metabolism, 94, (2), pp. 670-677. (doi:10.1210/jc.2008-2025). (PMID:19001513).

Record type: Article

Abstract

Context: production of 3-carbon units (as lactate) by granulosa cells (GCs) is important in follicular and oocyte development and may be modulated by metformin.

Objective: the aim of the study was to examine the action of metformin on GC lactate production and potential mediation via AMP-activated protein kinase (AMPK).

Design: GCs were prepared from follicular aspirates. After exposure to metformin and other potential modulators of AMPK in culture, aspects of cellular function were examined.

Setting: the study was conducted in a private fertility clinic/university academic center.

Patients: women undergoing routine in vitro fertilization participated in the study.

Interventions: all agents were added in culture.

Main outcome measures: lactate output of GCs was measured. Cell extracts were prepared after culture, and phosphorylated forms of AMPK and acetyl CoA carboxylase (ACC) were assayed using Western analysis.

Results: metformin led to a rapid increase in lactate production by GCs [minimum effective dose, 250 mu M; maximum dose studied, 1 mM (1.22-fold; P < 0.01)]. This dose range of metformin was similar to that required for stimulation of phospho-AMPK in GCs [minimum effective dose, 250 mu M; maximum effect, 500 mu M (2.01-fold; P < 0.001)]. Increasing phospho-ACC, as a representative downstream target regulated by AMPK, was apparent over a lower range (minimum effective dose, 31 mu M; maximum effect, 250 mu M; P < 0.001). A level of metformin (125 mu M) insufficient for the stimulation of lactate output when used alone potentiated the effects of suboptimal doses of insulin on lactate production. Adiponectin (2.5 mu g/ml) had a small but significant effect on lactate output.

Conclusions: metformin activates AMPK in GCs, stimulating lactate production and increasing phospho-ACC. Metformin also enhances the action of suboptimal insulin concentrations to stimulate lactate production. (J Clin Endocrinol Metab 94: 670-677, 2009

PDF AMPk_metformin_granulosa_cells_2009.pdf - Accepted Manuscript
Download (143kB)

More information

Published date: February 2009
Organisations: Dev Origins of Health & Disease

Identifiers

Local EPrints ID: 72698
URI: http://eprints.soton.ac.uk/id/eprint/72698
ISSN: 0021-972X
PURE UUID: 5eb96b25-4370-40a4-ae74-8f250582b658
ORCID for Iain T. Cameron: ORCID iD orcid.org/0000-0002-4875-267X

Catalogue record

Date deposited: 22 Feb 2010
Last modified: 18 Jul 2017 23:53

Export record

Altmetrics

Contributors

Author: Malcolm C. Richardson
Author: Susan Ingamells
Author: Chantal D. Simonis
Author: Iain T. Cameron ORCID iD
Author: Rajiv Sreekumar
Author: Ananth Vijendren
Author: Luckni Sellahewa

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×