Effects of pharmacological inhibition of AMP-activated protein kinase on GLUT3 expression and the development of ischemic tolerance in astrocytes

Abstract

Ischemic tolerance resulting from preconditioning ischemia is a neuroprotective mechanism. In cultured astrocytes, its development depends on regulation of the expression of glucose transporter 3 (GLUT3) by the stress sensor/effector AMP-activated protein kinase (AMPK). Here we demonstrate that GLUT3 is upregulated during preconditioning and then downregulated during recovery. We also found that, although AMPK inhibition during preconditioning initially suppressed the upregulation of GLUT3 as shown previously, this was followed by a period of GLUT3 upregulation, enhanced glycogen accumulation, and enhanced tolerance to a subsequent ischemic challenge. These results reveal that AMPK has a complex influence on ischemic tolerance.