Insulin-Regulated Aminopeptidase

Siew Yeen Chai, Ruani Fernando, Siying Ye, Grantley R. Peck, Anthony L Albiston

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Although insulin-regulated aminopeptidase (IRAP) was first described as a marker protein for specialized vesicles containing the insulin-responsive glucose transporter, GLUT4, the protein has subsequently been shown to be identical to oxytocinase or the AT4 receptor. In insulin responsive tissues, IRAP is almost exclusively co-localized with GLUT4, being retained in intracellular compartments in the basal state or translocating with GLUT4 to the plasma membrane under insulin stimulation. The function of IRAP in these tissues has not been elucidated — the protein is thought to be involved in the tethering of GLUT4 vesicles to intracellular compartments. In the placenta, IRAP was isolated as the enzyme that degrades oxytocin and is therefore thought to play a role in the prevention of premature labour and maintenance of an adequate blood flow to the uterus. Potentially the most exciting physiological role attributed to IRAP is the involvement of the enzyme in memory processing. AT4 ligands, upon binding to the catalytic site of IRAP, enhance spatial learning, facilitate memory retention and retrieval and reverse amnesia. We postulate that the AT4 ligands act via either one of these mechanisms: (1) The peptides bind to the catalytic site of IRAP and inhibit its enzymatic activity thereby prolonging the half-life of its neuropeptide substrates with memory-enhancing properties or (2) Upon binding to IRAP, the AT4 ligands regulate the level of GLUT4 expressed at the cell surface resulting in an increase in glucose uptake into neurones.
Original languageEnglish
Title of host publicationAminopeptidases in Biology and Disease
EditorsNigel M. Hooper, Uwe Lendeckel
Place of PublicationNew York, NY
Number of pages21
ISBN (Electronic)9781441988690
ISBN (Print)9781461346982
Publication statusPublished - 2004
Externally publishedYes

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