Stimulation of GLUT1 glucose transporter expression in response to inhibition of oxidative phosphorylation: role of reduced sulfhydryl groups

Role of 5′-AMP-activated protein kinase in stimulation of glucose transport in response to inhibition of oxidative phosphorylation

“…We also found that an imposed presumed increase in cell GSH-to-GSSG ratio was associated with an increase in the rate of glucose transport. However, and surprisingly, the stimulation of transport following inhibition of oxidative phosphorylation by azide was not inhibited by the addition of NAC, an intracellular reducing agent that counteracts ROS, or diamide, an intracellular sulfydryl oxidizing agent (3,33). The results indicate that whereas exposure to azide, ethanol, or lactate increases cell NADH-to-NAD ϩ ratio and stimulates ROS generation, the stimulation of glucose transport does not appear to be mediated by increased ROS generation.…”

“…In previous studies (9,18) we demonstrated that inhibition of oxidative phosphorylation by a variety of inhibitors and uncouplers leads to a stimulation of glucose transport. Moreover, the NADH-to-NAD ϩ ratio estimated by the ratio of lactate to pyruvate was increased under these conditions (3). We therefore tested whether an imposed increase in the above redox ratio produced by conditions not involving inhibition of oxidative phosphorylation is also associated with a stimulation of glucose transport.…”

“…*P Ͻ 0.05 compared with basal values. tive phosphorylation and that the effect is associated with a rise in cell NADH-to-NAD ϩ ratio estimated by an increase in intraand extracellular lactate-to-pyruvate ratio (3). An increase in NADH-to-NAD ϩ ratio is to be expected after inhibition of oxidative phosphorylation because the rise in the ratio helps sustain ATP synthesis through "anaerobic" glycolysis and lactate production (18,26).…”

“…Profound changes that occur after inhibition of oxidative phosphorylation by cyanide or azide include 1) a rapid fall in cell ATP level that returns to normal within an hour despite the continuous presence of the inhibitors (18,30), with ATP synthesis occurring by a marked stimulation of glucose transport and glycolysis (13,17,18); 2) an important change that occurs universally and sustains the enhanced rate of glycolysis, the changed redox state, with an increase in cytosolic NADHto-NAD ϩ ratio (3,16,32); and 3) stimulation of 5Ј-AMPactivated protein kinase (AMPK), which results from the associated changes in cell AMP-to-ATP ratio (1,10). However, whether any of the above changes is necessary and sufficient for the observed stimulation of glucose transport remains unknown.…”

Critical role of 5′-AMP-activated protein kinase in the stimulation of glucose transport in response to inhibition of oxidative phosphorylation

“…with stimulation of glucose transport and lactate production (5,14). More prolonged exposure to azide or CoCl 2 (a stimulator of the hypoxia-responsive pathway) results in an increase in Glut1 mRNA expression and subsequent enhanced Glut1 expression; however, this effect occurs only after ϳ4 h of exposure (6,11,23,24).…”