INSULIN INDUCTION OF PIP-92, CL-6, AND NOVEL MESSENGER-RNA IN RAT HEPATOMA-CELLS

Insulin directly affects many aspects of cellular metabolism. An addit ional, poorly studied effect of insulin is the regulation of multiple genes whose products are important in many cellular functions. Using d ifferential screening techniques, we identified insulin-regulated gene s induced in insulin-treated rat H4IIE (H4) hepatoma cells. Two of the mRNAs identified were homologous to the previously characterized mous e pip 92 and rat CL-6 immediate-early genes. The pip 92 clone was init ially isolated from mitogen-stimulated mouse Balb/c 3T3 fibroblasts, w hereas the CL-6 clone was first isolated from regenerating rat liver. In this article, we demonstrated that in rat H4 cells, the transcripti on rates of both pip 92 and CL-6 are induced by insulin alone. Additio nally, we showed that the transcription rates of two other genes, whos e sequences are not homologous to any other sequences in gene bank ('' novel genes''), were rapidly and transiently induced by insulin. These results demonstrate that insulin regulates the expression of several novel genes with a time-course similar to members of the immediate-ear ly response gene family.