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 ma intain the downhill gradient that results in movement of glucose into cells through the facilitative glucose transporters. GLUT4 and hexokin ase (HK) II are the major transporter and hexokinase isoforms in skele tal muscle, heart, and adipose tissue, wherein insulin promotes glucos e utilization. To understand whether hormones influence the contributi on of phosphorylation to cellular glucose utilization, we investigated the effects that catecholamines, cyclic AMP (cAMP), and insulin have on HKII gene expression in cells representative of muscle (L6 cells) a nd brown (BFC-1B cells) and white (3T3-F442A cells) adipose tissues. I soproterenol or the cAMP analog 8-chlorophenylthio-cAMP selectively in crease 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 evol ution. J Biol Chem 268:5209-5219, 1993), and cause a concentration- an d time-dependent increase of HKII mRNA in both muscle and fat cell lin es without changing HKI mRNA. Isoproterenol and insulin also increase the rate of synthesis of Hf(TI protein and increase glucose phosphoryl ation and glucose utilization in L6 cells.