REGULATION OF GAMMA-ACTIN GENE-EXPRESSION BY INSULIN

Insulin exerts rapid effects on cellular metabolism and can cause morphological changes by inducing rearrangements of cytoskeletal components. The regulation of specific cytoskeletal genes by insulin, however, has not been studied extensively. In the present work insulin was found to rapidly, but transiently, increase transcription of the cytoskeletal gamma-actin gene in rat H411E (H4) hepatoma cells. Insulin-induced transcription of the gamma-actin gene was evident within 5 min and was maximal by 15 min at 10-fold above control levels. The stimulation of transcription was transient, with a return towards basal levels by 120 min. Transcription of gamma-actin was increased at insulin concentrations as low as 1 x 10(-11) 1 M and was maximal at 1 x 10(-9) to 1 x 10(-8) M. Transcription of several control genes (skeletal and cardiac alpha-actin and beta-tubulin) were unaltered by insulin administration. Messenger RNA (mRNA) levels for the gamma-actin gene increased, but to a lesser degree than transcription. Since the gamma-actin message is an abundant and stable mRNA, its levels would not be expected to change dramatically from a transient induction of transcription. Like insulin, phorbol esters transiently in creased transcription of the gamma-actin gene. In addition, pretreatment of cells with phorbol esters for 24 h reduced the ability of insulin to induce gamma-actin transcription. These data support our hypothesis that insulin and phorbol esters share intracellular signalling pathways in the control of transcription of specific genes. (C) 1994 Wiley-Liss, Inc.