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2013 | 60 | 4 | 607-612
Article title

Metformin reduces NAD(P)H oxidase activity in mouse cultured podocytes through purinergic dependent mechanism by increasing extracellular ATP concentration

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EN
Abstracts
EN
Hyperglycemia affects the functioning numbers of podocytes and leads to a gradual decline of renal function. The normalization of glucose level is a principle therapeutic goal in diabetic patients and metformin is a popular hypoglycemic drug used in type 2 diabetes mellitus. Metformin activates AMP-activated kinase (AMPK) and decreases NAD(P)H oxidase activity in podocytes leading to reduction of free radical generation. Similar effects are observed after activation of P2 receptors. Therefore, we investigated whether metformin increases extracellular ATP concentration and affects the activities of NAD(P)H oxidase and AMPK through P2 receptors. Experiments were performed on cultured mouse podocytes. NAD(P)H oxidase activity was measured by chemiluminescence and changes in AMPK activity were estimated by immunoblotting against AMPKα-Thr172-P. Metformin increased extracellular ATP concentration by reduction of ecto-ATPase activity, decreased NAD(P)H oxidase activity and increased AMPK phosphorylation. A P2 receptor antagonist, suramin (300 µM), prevented metformin action on NAD(P)H oxidase and AMPK phosphorylation. The data suggests a novel mechanism of metformin action, at least in podocytes. Metformin, which increases extracellular ATP concentration leads to activation of P2 receptors and consequent modulation of the podocytes' metabolism through AMPK and NAD(P)H oxidase which, in turn, may affect podocyte functioning.
Year
Volume
60
Issue
4
Pages
607-612
Physical description
Dates
published
2013
received
2013-06-28
revised
2013-08-30
accepted
2013-09-02
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Document Type
Publication order reference
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv60p607kz
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