Insulinase

In 1950, Mirsky and Broh-Kahn were the first to describe an enzyme capable of degrading insulin and named it "insulinase" (Hoppe-Seyler 1967 / Flacke 1975).

The IUBMB (International Union of Biochemistry and Molecular Biology) renamed it "insulysin" in 1992 (Leal 2013).

Insulinase is an enzyme that primarily breaks down insulin. It can also break down (but more slowly than insulin):

• growth factor (IGF) I and II
• Amylin
• β-amyloid (Aβ) peptide
• Aβ-precursor protein intracellular domain (APP-AICD).
• Amyloid Bri (Abri)
• amyloid Dan (Adan)
• atrial natriuretic peptide
• β-endorphin
• Calcitonin
• chemokine ligand (CCL)3 and CCL4
• cytochrome c
• glucagon
• oxidized hemoglobin
• transforming growth factor- α (TGF- α)
• Growth hormone releasing factor (Najjar 2019).

The term "insulinase" is outdated, nowadays the term "insulysin" = IDE is increasingly used (Leal 2013).

IDE is found in all tissues, especially in liver, brain and muscle (Ciaccio 2009) . There, it is predominantly localized in the cytosol (Leissring 2021).

IDE acts up to a maximum of 39 degrees and pH 7.5 (Lohmann 1956).

Studies in pregnant women have shown that insulinase is also produced in the placenta (Lehmann 2006).

Pharmacodynamics : IDE degrades insulin on the one hand by splitting into an A and B chain and on the other hand by proteolysis (Hoffmann La Roche 2003) 931

• Hyperinsulinemia: Prolonged inhibition of IDE leads to chronic hyperinsulinemia with secondary insulin resistance and impaired insulin secretion (Najjar 2019).
• Insulin secretion: There is now evidence for type 2 diabetics of an association between low levels of IDE and lower insulin secretion. Also, studies found lower IDE- activity as well as lower insulin depletion in subcutaneous and especially visceral fat depots in pre-diabetics and type 2 di abetics compared to non-diabetics. In contrast, no change in IDE activity was found in well-controlled type 1 di abetics. The effects of obesity on IDE- levels and insulin secretion are controversial to date (Najjar 2019).
• Alzheimer's disease: Impaired clearance of amyloid beta is considered one of the main causes of Alzheimer's disease. IDE is considered a proteolytic inducer of various extracellular and intracellular beta-forming peptides (Kurochkin 2018)and is critically involved in the maintenance of amyloid- beta concentration in the brain (de Tullio 2008).

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