Insulin-regulated aminopeptidase inhibitors do not alter glucose handling in normal and diabetic rats

• Published in: Journal of molecular endocrinology Vol. 58; no. 4; pp. 193 - 198
• Main Authors: Albiston, Anthony L, Cacador, Mauricio, Sinnayah, Puspha, Burns, Peta, Chai, Siew Yeen
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.05.2017; Society for Endocrinology & BioScientifica Ltd
• Subjects: Adipocytes; Aminopeptidase; Animals; Biological Transport; Cell Differentiation; Cell Line; Cystinyl Aminopeptidase - antagonists & inhibitors; Cystinyl Aminopeptidase - genetics; Cystinyl Aminopeptidase - metabolism; Deoxyglucose - pharmacology; Diabetes mellitus; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - enzymology; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - pathology; Gene Expression Regulation; Glucose; Glucose - metabolism; Glucose transporter; Glucose Transporter Type 4 - genetics; Glucose Transporter Type 4 - metabolism; Homeostasis; Insulin; Insulin - metabolism; Insulin - pharmacology; Male; Myoblasts - cytology; Myoblasts - drug effects; Myoblasts - metabolism; Protease Inhibitors - pharmacology; Rats; Rats, Sprague-Dawley; Signal Transduction; Streptozocin; glucose; IRAP; GLUT4; diabetes; aminopeptidase
• ISSN: 0952-5041; 1479-6813
• DOI: 10.1530/JME-17-0033

Insulin-regulated aminopeptidase (IRAP) co-localizes with the glucose transporter 4 (GLUT4) in GLUT4 storage vesicles (GSV) in insulin-responsive cells. In response to insulin, IRAP is the only transmembrane enzyme known to translocate together with GLUT4 to the plasma membrane in adipocytes and muscle cells. Although the intracellular region of IRAP is associated with GLUT4 vesicle trafficking, the role of the aminopeptidase activity in insulin-responsive cells has not been elucidated. The aim of this study was to investigate whether the inhibition of the aminopeptidase activity of IRAP facilitates glucose uptake in insulin-responsive cells. In both in vitro and in vivo studies, inhibition of IRAP aminopeptidase activity with the specific inhibitor, HFI-419, did not modulate glucose uptake. IRAP inhibition in the L6GLUT4myc cell line did not alter glucose uptake in both basal and insulin-stimulated state. In keeping with these results, HFI419 did not affect peripheral, whole-body glucose handling after an oral glucose challenge, neither in normal rats nor in the streptozotocin (STZ)-induced experimental rat model of diabetes mellitus (DM). Therefore, acute inhibition of IRAP aminopeptidase activity does not affect glucose homeostasis.