Cellular distribution of insulin-degrading enzyme gene expression. Comparison with insulin and insulin-like growth factor receptors

Abstract

Insulin-degrading enzyme (IDE) hydrolyzes both insulin and IGFs and has been proposed to play a role in signal termination after binding of these peptides to their receptors. In situ hybridization was used to investigate the cellular distribution of IDE mRNA and to compare it with insulin receptor (IR) and IGF-I receptor (IGFR) gene expression in serial thin sections from a variety of tissues in embryonic and adult rats. IDE mRNA is highly abundant in kidney and liver, tissues known to play a role in insulin degradation. IDE and IR mRNAs are highly coexpressed in brown fat and liver. The highest level IDE gene expression, on a per cell basis, is found in germinal epithelium. IDE and IGFR mRNAs are colocalized in oocytes, while IDE is colocalized with the IGF-II receptor in spermatocytes, suggesting that IDE may be involved with degradation of IGF-II in the testis. In summary, IDE expression demonstrates significant anatomical correlation with insulin/IGF receptors. These data are compatible with a role for IDE in degrading insulin and IGFs after they bind to and are internalized with their respective receptors and may also suggest a novel role for IDE in germ cells.