What is the Origin of Insulin-Degrading Enzyme?

This enzyme was first identified and characterized in the mid-20th century due to its ability to rapidly inactivate insulin in tissue extracts. Initially termed insulinase, its broader substrate specificity and precise molecular structure were later elucidated, leading to its current nomenclature. Research into IDE remains a significant focus in endocrinology and neurobiology, exploring its dual role in metabolic regulation and neurodegenerative disease.

What is the Mechanism of Insulin-Degrading Enzyme?

IDE functions as a proteolytic enzyme, utilizing a zinc ion within its active site to hydrolyze the peptide bonds of its substrate proteins, including insulin. The enzyme's efficiency is modulated by its cellular location and the local concentration of its substrates. In the context of insulin signaling, IDE acts as a crucial negative regulator; after insulin binds to its receptor and initiates cellular glucose uptake, IDE rapidly degrades the internalized insulin molecule, ensuring a precise and transient signal duration. Variations in IDE activity can significantly impact the systemic insulin load and contribute to insulin resistance.

Insulin-Degrading Enzyme ∞ Area

Insulin-Degrading Enzyme

Meaning

Insulin-Degrading Enzyme (IDE) is a ubiquitous metalloprotease found in the cytosol of most mammalian cells, with a high concentration in the liver, kidney, and brain. Its primary physiological role is the termination of insulin signaling by cleaving the insulin peptide, thereby regulating the circulating half-life and local concentration of the hormone. Beyond insulin, IDE also degrades several other important peptide hormones and amyloidogenic proteins, including the amyloid-beta peptide implicated in Alzheimer’s disease. The enzyme’s activity is a critical determinant of insulin sensitivity and metabolic clearance.