The insulin-degrading enzyme as a link between insulin and neuropeptides metabolism

We have applied a recently developed HPLC-MS enzymatic assay to investigate the cryptic peptides generated by the action of the insulin-degrading enzyme (IDE) on some neuropeptides (NPs) involved in the development of tolerance and dependence to opioids. Particularly, the tested NPs are generated fr...

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Main Authors: Dorota Wacławczyk, Jerzy Silberring, Giuseppe Grasso
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
Subjects:
Online Access:http://dx.doi.org/10.1080/14756366.2020.1850712
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author Dorota Wacławczyk
Jerzy Silberring
Giuseppe Grasso
author_facet Dorota Wacławczyk
Jerzy Silberring
Giuseppe Grasso
author_sort Dorota Wacławczyk
collection DOAJ
description We have applied a recently developed HPLC-MS enzymatic assay to investigate the cryptic peptides generated by the action of the insulin-degrading enzyme (IDE) on some neuropeptides (NPs) involved in the development of tolerance and dependence to opioids. Particularly, the tested NPs are generated from the NPFF precursor (pro-NPFF (A)): NPFF (FLFQPQRF) and NPAF (AGEGLSSPFWSLAAPQRF). The results show that IDE is able to cleave NPFF and NPAF, generating specific cryptic peptides. As IDE is also responsible for the processing of many other peptides in the brain (amyloid beta protein among the others), we have also performed competitive degradation assays using mixtures of insulin and the above mentioned NPs. Data show that insulin is able to slow down the degradation of both NPs tested, whereas, surprisingly, NPAF is able to accelerate insulin degradation, hinting IDE as the possible link responsible of the mutual influence between insulin and NPs metabolism.
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spelling doaj.art-6d5f477dd101498794ff6e43560ece512022-12-21T19:34:21ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-0136118318710.1080/14756366.2020.18507121850712The insulin-degrading enzyme as a link between insulin and neuropeptides metabolismDorota Wacławczyk0Jerzy Silberring1Giuseppe Grasso2Department of Biochemistry and Neurobiology, AGH University of Science and TechnologyDepartment of Biochemistry and Neurobiology, AGH University of Science and TechnologyDepartment of Chemical Sciences, University of CataniaWe have applied a recently developed HPLC-MS enzymatic assay to investigate the cryptic peptides generated by the action of the insulin-degrading enzyme (IDE) on some neuropeptides (NPs) involved in the development of tolerance and dependence to opioids. Particularly, the tested NPs are generated from the NPFF precursor (pro-NPFF (A)): NPFF (FLFQPQRF) and NPAF (AGEGLSSPFWSLAAPQRF). The results show that IDE is able to cleave NPFF and NPAF, generating specific cryptic peptides. As IDE is also responsible for the processing of many other peptides in the brain (amyloid beta protein among the others), we have also performed competitive degradation assays using mixtures of insulin and the above mentioned NPs. Data show that insulin is able to slow down the degradation of both NPs tested, whereas, surprisingly, NPAF is able to accelerate insulin degradation, hinting IDE as the possible link responsible of the mutual influence between insulin and NPs metabolism.http://dx.doi.org/10.1080/14756366.2020.1850712insulin-degrading enzymeneuropeptidesdiabetesopiods
spellingShingle Dorota Wacławczyk
Jerzy Silberring
Giuseppe Grasso
The insulin-degrading enzyme as a link between insulin and neuropeptides metabolism
Journal of Enzyme Inhibition and Medicinal Chemistry
insulin-degrading enzyme
neuropeptides
diabetes
opiods
title The insulin-degrading enzyme as a link between insulin and neuropeptides metabolism
title_full The insulin-degrading enzyme as a link between insulin and neuropeptides metabolism
title_fullStr The insulin-degrading enzyme as a link between insulin and neuropeptides metabolism
title_full_unstemmed The insulin-degrading enzyme as a link between insulin and neuropeptides metabolism
title_short The insulin-degrading enzyme as a link between insulin and neuropeptides metabolism
title_sort insulin degrading enzyme as a link between insulin and neuropeptides metabolism
topic insulin-degrading enzyme
neuropeptides
diabetes
opiods
url http://dx.doi.org/10.1080/14756366.2020.1850712
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