Metformin induces up-regulation of blood-brain barrier functions by activating AMP-activated protein kinase in rat brain microvascular endothelial cells.

Fuyuko Takata, Shinya Dohgu, Junichi Matsumoto, Takashi Machida, Shuji Kaneshima, Mai Matsuo, Shinya Sakaguchi, Yuki Takeshige, Atsushi Yamauchi, Yasufumi Kataoka

Index: Biochem. Biophys. Res. Commun. 433(4) , 586-90, (2013)

Full Text: HTML

Abstract

Blood-brain barrier (BBB) disruption occurs frequently in CNS diseases and injuries. Few drugs have been developed as therapeutic candidates for facilitating BBB functions. Here, we examined whether metformin up-regulates BBB functions using rat brain microvascular endothelial cells (RBECs). Metformin, concentration- and time-dependently increased transendothelial electrical resistance of RBEC monolayers, and decreased RBEC permeability to sodium fluorescein and Evans blue albumin. These effects of metformin were blocked by compound C, an inhibitor of AMP-activated protein kinase (AMPK). AMPK stimulation with an AMPK activator, AICAR, enhanced BBB functions. These findings indicate that metformin induces up-regulation of BBB functions via AMPK activation.Copyright © 2013 Elsevier Inc. All rights reserved.