Immunohistochemical evidence of ubiquitous distribution of the metalloendoprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cell lines

Abstract

Immunohistochemical evidence for ubiquitous distribution of metalloprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cells is presented. Immunohistochemical staining was performed on a multi-organ tissue microarray (pancreas, lung, kidney, central/peripheral nervous system, liver, breast, placenta, myocardium, striated muscle, bone marrow, thymus, spleen) and on a cell microarray encompassing 31 tumor cell lines of different origin plus trophoblast cells, and normal blood lymphocytes and granulocytes. IDE protein is expressed by all of the tissues assessed and in all of the tumor cell lines except Raji and HL-60; trophoblast cells and granulocytes but not normal lymphocytes are also IDE-positive.

Insulin as an immunomodulatory hormone

“…As mentioned, inflammatory mediators may potentiate glucagon, suggesting another indirect mechanism by which inflammatory mediators may increase IDE activity. Interestingly, though IDE is ubiquitously expressed in various human tissue, it is not expressed in circulating lymphocytes but rather in other immune cells such as alveolar macrophages [113]. While IDE has diverse functions, it is not known if this expression pattern correlates with insulin removal.…”

Human proinsulin production in the milk of transgenic cattle

“…The alignments found by Protein BLAST analysis suggest, despite the mutation, that this peptide must correspond to bovine IDE since a low percentage of query cover and identity were found with peptides from other bovine proteins. In addition, IDE is present in the duct epithelia of the mammary gland of the human breast 30,31 …”

“…In addition, IDE is present in the duct epithelia of the mammary gland of the human breast. 30,31 Milk proteases hydrolyze milk proteins inside the mother's mammary gland and in the stomach of term infants, producing bioactive peptides. 32 Several proteases have been reported to be active in the human milk of preterm-delivering mothers, such as carboxypeptidase B2, kallikrein, plasmin, elastase, thrombin, and aminopeptidase.…”

Insulin-Degrading Enzyme, an Under-Estimated Potential Target to Treat Cancer?

“…The first protein expression of IDE was measured by cell microarray in more than thirty human tumor cell lines by Schmitt et al Expression of IDE was confirmed in all tested lines from solid and blood tumors, except two cell lines (Raji lymphoma cells and HL-60 leukemia cells) [ 82 , 83 ]. More interestingly, overexpression of IDE was observed by immunochemistry in malignant human breast cells [ 84 ].…”