Insulin-degrading enzyme (IDE) (IDE)

Insulin-degrading enzyme (IDE), also known as insulysin, is a highly conserved 110 kDa zinc-metallopeptidase that acts as the primary enzyme responsible for the clearance of insulin and several other bioactive peptides. It belongs to the M16 family of metalloproteases and is ubiquitously expressed in tissues such as the liver, kidney, and brain, where it localizes to the cytosol, endosomes, and mitochondria. Beyond its titular role in insulin catabolism, IDE is a critical regulator of amyloid-beta (Aβ) levels, positioning it as a key link between metabolic regulation and neurodegeneration. In the context of Type 2 diabetes mellitus, pharmacological inhibition of IDE is being investigated to prolong the half-life of insulin and improve glucose homeostasis. Conversely, in Alzheimer's disease research, activators of IDE are explored for their potential to enhance the clearance of neurotoxic amyloid plaques. However, the enzyme's broad substrate specificity—which includes glucagon, amylin, and natriuretic peptides—presents significant therapeutic challenges, as non-selective modulation can lead to adverse effects like paradoxical glucose intolerance or accelerated protein aggregation.

Other names

InsulysinInsulinaseAbeta-degrading proteaseAmyloid beta-degrading enzymeInsulin-degrading neutral proteinase

Inhibitors prolong the half-life of insulin and other substrates to enhance insulin signaling and improve glucose uptake; activators increase the rate of amyloid-beta degradation to reduce neurotoxicity and plaque formation.