Enhancement of glucose transport in response to inhibition of oxidative metabolism: pre- and posttranslational mechanisms

Addition of 5 mM sodium azide to Clone 9 cells, a rat liver cell line characterized by intracellular glucose concentrations of less than 10% that of the external medium and limited glycogen stores, results in a 50-80% reduction in cell ATP content within 20 min which then recovers to near-basal levels within 1 h and is subsequently maintained at normal levels for 24 h despite continuing the presence of the inhibitor. Associated with this adaptive response is a striking stimulation of facilitated glucose transport, mediated by the GLUT-1 transporter, that exhibits "early" and "late" phases that appear to be mechanistically different. During the early phase of the response (0-2 h), glucose transport rate is enhanced 12-fold in the absence of any change in cell GLUT-1 or GLUT-1 mRNA content. In contrast, the late phase of the response (8-24 h) is characterized by a further large stimulation of glucose transport (to 1.6 times the 2-h value) that is associated with 2- to 3- and 6- to 10-fold increments in cell GLUT-1 and GLUT-1 mRNA content, respectively. In time course studies an increase in GLUT-1 mRNA content was observed at 4 h and preceded the increment in GLUT-1 which became detectable after 8 h of exposure to azide. A marked induction of GLUT-1 mRNA by azide was also demonstrable in cells incubated in medium containing higher concentrations of glucose (10.6 mM), although the increment was approximately 20% less than when cells were incubated in standard medium (containing 5.6 mM glucose).(ABSTRACT TRUNCATED AT 250 WORDS)