Insulin induction of c-Ki-ras in rat liver and in cultured normal rat hepatocytes.

1. Insulin administration in neonatal rats causes a dramatic accumulation of the major c-Ki-ras transcript. 2. The level of c-Ki-ras transcript is greatly reduced in alloxan-induced diabetic rats. 3. Injection of insulin in alloxan-induced diabetic rats is able to restore almost completely the level of c-Ki-ras transcript found in insulin-induced normal rats. 4. Results from nuclear run-off experiments reveal that the inductive effect of insulin is at the level of transcription of the c-Ki-ras gene. 5. As in whole animals, insulin is also able to induce the expression of c-Ki-ras in cultured normal hepatocytes. 6. This inductive effect of insulin is markedly reduced in hepatocytes which have been previously treated with the tumour promoter, 12-O-tetradecanoylphorbol-13 acetate for 24 hr, a result suggesting that at least part of the effect of insulin is mediated via protein kinase C.