Multiple functions of insulin-degrading enzyme: a metabolic crosslight?

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Tundo GR, Sbardella D, Ciaccio C, Grasso G, Gioia M, Coletta A, Polticelli F, Di Pierro D, Milardi D, Van Endert P, Marini S, Coletta M

Multiple functions of insulin-degrading enzyme: a metabolic crosslight?

Crit Rev Biochem Mol Biol. 2017 Oct;52(5):554-582. doi: 10.1080/10409238.2017.1337707. Epub 2017 Jun 21.

PubMed ID

28635330 [ View in PubMed

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Abstract

Insulin-degrading enzyme (IDE) is a ubiquitous zinc peptidase of the inverzincin family, which has been initially discovered as the enzyme responsible for insulin catabolism; therefore, its involvement in the onset of diabetes has been largely investigated. However, further studies on IDE unraveled its ability to degrade several other polypeptides, such as beta-amyloid, amylin, and glucagon, envisaging the possible implication of IDE dys-regulation in the "aggregopathies" and, in particular, in neurodegenerative diseases. Over the last decade, a novel scenario on IDE biology has emerged, pointing out a multi-functional role of this enzyme in several basic cellular processes. In particular, latest advances indicate that IDE behaves as a heat shock protein and modulates the ubiquitin-proteasome system, suggesting a major implication in proteins turnover and cell homeostasis. In addition, recent observations have highlighted that the regulation of glucose metabolism by IDE is not merely based on its largely proposed role in the degradation of insulin in vivo. There is increasing evidence that improper IDE function, regulation, or trafficking might contribute to the etiology of metabolic diseases. In addition, the enzymatic activity of IDE is affected by metals levels, thus suggesting a role also in the metal homeostasis (metallostasis), which is thought to be tightly linked to the malfunction of the "quality control" machinery of the cell. Focusing on the physiological role of IDE, we will address a comprehensive vision of the very complex scenario in which IDE takes part, outlining its crucial role in interconnecting several relevant cellular processes.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Zinc acetate	Insulin-degrading enzyme	Protein	Humans	Unknown	Ligand	Details
Zinc chloride	Insulin-degrading enzyme	Protein	Humans	Unknown	Cofactor	Details
Zinc sulfate, unspecified form	Insulin-degrading enzyme	Protein	Humans	Unknown	Cofactor	Details