EFFECT OF DEXAMETHASONE ON THE ALTERNATIVE SPLICING OF THE INSULIN-RECEPTOR MESSENGER-RNA AND INSULIN ACTION IN HEPG2 HEPATOMA-CELLS

We have shown that culturing HepG2 cells in Ham's F-12 medium suppleme nted with calf serum, dexamethasone, and triiodothyronine causes an in crease in the insulin sensitivity and responsiveness for glucose incor poration into glycogen. This correlates with increased expression of t he mRNA encoding the B isoform of the insulin receptor. Of all the com ponents in the medium, we found that dexamethasone exerted the greates t effect. Dexamethasone alone could cause both a switch in expression from the A to the B isoform of the insulin receptor and also an increa se in insulin sensitivity for both glucose incorporation into glycogen and 2-deoxyglucose transport. In addition, we found that expression o f the B isoform of the insulin receptor is developmentally regulated i n the 3T3-L1 adipocyte leading to the suggestion that the alternativel y 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.