Insulin downregulates the steady-state level of its receptor's messenger ribonucleic acid

The effects of insulin on the steady-state level of human insulin receptor (hIR) mRNA were examined in the HepG2 human liver cell line using Northern blot analysis of either total cellular or poly(A)+ RNA. In control cells, up to six (4.5, 5.2, 7.4, 8.5, 9.4 and 10.8 kb) hybridizable species of hIR mRNA were identified, with the 8.5 and 10.8 kb species being most prominent. Incubation for 18 hrs with 1 microM insulin resulted in a similar decrease (to approximately 35% of control) of all the hIR mRNA species. The insulin effect was dose-dependent and was half-maximal by 2-3 hrs and maximal by 4-6 hrs of incubation at 37 degrees C. The hIR mRNA levels remained maximally insulin suppressed for up to 18 hrs but thereafter the effect became attenuated. These results indicate that insulin downregulates the level of hIR mRNA with a biphasic time-course and that this process is most likely part of the general mechanism by which insulin maintains the homeostatic control of its cellular receptor levels.