Regulation of Hexokinase II Gene Transcription and Glucose Phosphorylation by Catecholamines, Cyclic AMP, and Insulin

The hexokinases, by converting glucose to glucose-6-phosphate, help maintain the downhill gradient that results in movement of glucose into cells through the facilitative glucose transporters. GLUT4 and hexokinase (HK) II are the major transporter and hexokinase isoforms in skeletal muscle,heart, and adipose tissue, wherein insulin promotes glucose utilization. To understand whether hormones influence the contribution of phosphorylation to cellular glucose utilization, we investigated the effects that catecholamines, cyclic AMP (cAMP), and insulin have on HKII gene expression incells representative of muscle (L6 cells) and brown (BFC-1B cells) and white (3T3-F442A cells) adipose tissues. Isoproterenol or the cAMP analog 8-chlorophenylthio-cAMP selectively increase HKII gene transcription in L6 cells, as does insulin (Printz RL, Koch S, Potter LP, O'Doherty RM,Tiesinga JJ, Moritz S, Granner DK: Hexokinase II mRNA and gene structure, regulation by insulin, and evolution. J Biol Chem 268:5209–5219, 1993), and cause a concentration- and time-dependent increase of HKII mRNA in both muscle and fat cell lines without changing HKI mRNA. Isoproterenol and insulin also increase the rate of synthesis of HKII protein and increase glucose phosphorylation and glucose utilization in L6 cells.