CELLULAR-DISTRIBUTION OF INSULIN-DEGRADING ENZYME GENE-EXPRESSION - COMPARISON WITH INSULIN AND INSULIN-LIKE GROWTH-FACTOR RECEPTORS

Insulin-degrading enzyme (IDE) hydrolyzes both insulin and IGFs and ha s been proposed to play a role in signal termination after binding of these peptides to their receptors. In situ hybridization was used to i nvestigate the cellular distribution of IDE mRNA and to compare it wit h insulin receptor (IR) and IGF-I receptor (IGFR) gene expression in s erial thin sections from a variety of tissues in embryonic and adult r ats. IDE mRNA is highly abundant in kidney and liver, tissues known to play a role in insulin degradation. IDE and IR mRNAS are highly coexp ressed in brown fat and liver. The highest level IDE gene expression, on a per cell basis, is found in germinal epithelium. IDE and IGFR mRN As are colocalized in oocytes, while IDE is colocalized with the IGF-I I receptor in spermatocytes, suggesting that IDE may be involved with degradation of IGF-II in the testis. In summary, IDE expression demons trates 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 re ceptors and may also suggest a novel role for IDE in germ cells.