Effect of dexamethasone on the alternative splicing of the insulin receptor mRNA and insulin action in HepG2 hepatoma cells.

We have shown that culturing HepG2 cells in Ham's F-12 medium supplemented with calf serum, dexamethasone, and triiodothyronine causes an increase in the insulin sensitivity and responsiveness for glucose incorporation into glycogen. This correlates with increased expression of the mRNA encoding the B isoform of the insulin receptor. Of all the components in the medium, we found that dexamethasone exerted the greatest effect. Dexamethasone alone could cause both a switch in expression from the A to the B isoform of the insulin receptor and also an increase in insulin sensitivity for both glucose incorporation into glycogen and 2-deoxyglucose transport. In addition, we found that expression of the B isoform of the insulin receptor is developmentally regulated in the 3T3-L1 adipocyte leading to the suggestion that the alternatively spliced B isoform of the insulin receptor may play an important role in signal transduction in insulin target tissues such as liver, fat, and muscle.