Insulin-degrading Enzyme (IDE)

Abstract

Background: Insulin-degrading enzyme (IDE) is a highly conserved metallopeptidase initially described because of its ability to degrade insulin. Results: (i) IDE expression is stress-inducible; (ii) IDE concentration is up-regulated in some CNS tumors; (iii) IDE downregulation impairs SHSY5Y cell proliferation/viability. Conclusion: IDE is a multifunctional protein.Significance: IDE is a novel HSP with important implications in cell growth regulation.

Targeting Insulin-Degrading Enzyme to Treat Type 2 Diabetes Mellitus

“…IDE is expressed in all tissues and its levels can be modulated by many signals, including cellular stress, glucagon, and free fatty acids [4, 8, 9]. It is localized in the cytosol and growing evidence indicates that its proteolytic activity is subjected to complicated regulation inside cells.…”

Loss of renal SNX5 results in impaired IDE activity and insulin resistance in mice

“…lysosomes), as reported in the liver [13, 14]. Protein disulfide isomerase and cathepsin D are involved in insulin metabolism but IDE is the major enzyme responsible for degrading insulin [15, 16]; Ide null mice display hyperinsulinaemia and glucose intolerance [17]. …”

“…Treatment of hippocampal neurons with the phosphoinositide 3-kinase inhibitors wortmannin and LY 294002 blunts the upregulation of IDE caused by insulin [18]. By contrast, all trans -retinoic acid decreases IDE expression and activity in several neuroblastoma cell lines [16]. However, the renal mechanisms involved in the regulation of IDE expression are not known.…”

Metabolism of Cryptic Peptides Derived from Neuropeptide FF Precursors: The Involvement of Insulin-Degrading Enzyme

“…Moreover, the transgenic overexpression of IDE results in lowered Aβ levels and reduced or completely prevented the plaque formation observed in AD [ 21 ]. More recently, it has been reported that IDE, apart from regulating insulin [ 22 ] and Aβ peptides levels [ 23 ], is overexpressed in vivo in tumors of the CNS, and a novel role for IDE as a heat shock protein has also been proposed [ 24 ].…”