Insulin-inducible changes in insulin receptor mRNA splice variants.

Alternative splicing of insulin receptor pre-mRNA has been shown to be regulated in a tissue-specific and developmental manner. We investigated whether the receptor ligand might regulate the relative distribution of alternatively spliced mRNA in insulin-sensitive cells and found that changes in the relative expression of the two alternatively spliced insulin receptor RNA isotypes expressed in hepatocytes are regulated by insulin. In addition, we observed significant differences (p < or = 0.001) in insulin receptor isotype expression in subjects who were hyperinsulinemic and insulin-resistant versus subjects who were insulin-sensitive. These results support a role for insulin in the regulation of the relative expression of alternatively spliced mRNA expressed in insulin-responsive cells and tissues.