Development and characterisation of a peptidergic N-and C-terminally stabilised mammalian NPY1R agonist which protects against diabetes induction.
Identifieur interne : 000112 ( Main/Exploration ); précédent : 000111; suivant : 000113Development and characterisation of a peptidergic N-and C-terminally stabilised mammalian NPY1R agonist which protects against diabetes induction.
Auteurs : Ryan A. Lafferty [Royaume-Uni] ; Neil Tanday [Royaume-Uni] ; Peter R. Flatt [Royaume-Uni] ; Nigel Irwin [Royaume-Uni]Source :
- Biochimica et biophysica acta. General subjects [ 1872-8006 ] ; 2020.
Descripteurs français
- KwdFr :
- Agents protecteurs (composition chimique), Agents protecteurs (usage thérapeutique), Animaux (MeSH), Cellules à insuline (effets des médicaments et des substances chimiques), Cellules à insuline (métabolisme), Diabète expérimental (métabolisme), Diabète expérimental (prévention et contrôle), Diabète expérimental (traitement médicamenteux), Hypoglycémiants (composition chimique), Hypoglycémiants (usage thérapeutique), Insuline (métabolisme), Lignée cellulaire (MeSH), Mâle (MeSH), Peptides (composition chimique), Peptides (usage thérapeutique), Petromyzon (MeSH), Protéines de poisson (composition chimique), Protéines de poisson (usage thérapeutique), Récepteur neuropeptide Y (agonistes), Récepteur neuropeptide Y (métabolisme), Souris (MeSH).
- MESH :
- agonistes : Récepteur neuropeptide Y.
- composition chimique : Agents protecteurs, Hypoglycémiants, Peptides, Protéines de poisson.
- effets des médicaments et des substances chimiques : Cellules à insuline.
- métabolisme : Cellules à insuline, Diabète expérimental, Insuline, Récepteur neuropeptide Y.
- prévention et contrôle : Diabète expérimental.
- traitement médicamenteux : Diabète expérimental.
- usage thérapeutique : Agents protecteurs, Hypoglycémiants, Peptides, Protéines de poisson.
- Animaux, Lignée cellulaire, Mâle, Petromyzon, Souris.
English descriptors
- KwdEn :
- Animals (MeSH), Cell Line (MeSH), Diabetes Mellitus, Experimental (drug therapy), Diabetes Mellitus, Experimental (metabolism), Diabetes Mellitus, Experimental (prevention & control), Fish Proteins (chemistry), Fish Proteins (therapeutic use), Hypoglycemic Agents (chemistry), Hypoglycemic Agents (therapeutic use), Insulin (metabolism), Insulin-Secreting Cells (drug effects), Insulin-Secreting Cells (metabolism), Male (MeSH), Mice (MeSH), Peptides (chemistry), Peptides (therapeutic use), Petromyzon (MeSH), Protective Agents (chemistry), Protective Agents (therapeutic use), Receptors, Neuropeptide Y (agonists), Receptors, Neuropeptide Y (metabolism).
- MESH :
- chemical , agonists : Receptors, Neuropeptide Y.
- chemical , chemistry : Fish Proteins, Hypoglycemic Agents, Peptides, Protective Agents.
- drug effects : Insulin-Secreting Cells.
- drug therapy : Diabetes Mellitus, Experimental.
- metabolism : Diabetes Mellitus, Experimental, Insulin, Insulin-Secreting Cells, Receptors, Neuropeptide Y.
- prevention & control : Diabetes Mellitus, Experimental.
- chemical , therapeutic use : Fish Proteins, Hypoglycemic Agents, Peptides, Protective Agents.
- Animals, Cell Line, Male, Mice, Petromyzon.
Abstract
BACKGROUND
PYY (1-36) peptides from phylogenetically ancient fish, such as sea lamprey, have previously been shown to function as specific neuropeptide Y1 receptor (NPYR1) agonists. Although, sea lamprey PYY (1-36) is N-terminally stable, we reveal in this study that the peptide is subject to endopeptidase mediated C-terminal dipeptide degradation. In an attempt to prevent this, (d-Arg
METHODS
In vitro bioassays assessed enzymatic stability, insulinostatic activity as well as beta-cell anti-apoptotic actions of (d-Arg
RESULTS
(d-Arg
CONCLUSION
We present (d-Arg
GENERAL SIGNIFICANCE
Enzymatically stable, long-acting PYY (1-36) peptides highlight the therapeutic benefits of sustained activation of NPYR1's in diabetes.
DOI: 10.1016/j.bbagen.2020.129543
PubMed: 32007578
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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<term>Cell Line (MeSH)</term>
<term>Diabetes Mellitus, Experimental (drug therapy)</term>
<term>Diabetes Mellitus, Experimental (metabolism)</term>
<term>Diabetes Mellitus, Experimental (prevention & control)</term>
<term>Fish Proteins (chemistry)</term>
<term>Fish Proteins (therapeutic use)</term>
<term>Hypoglycemic Agents (chemistry)</term>
<term>Hypoglycemic Agents (therapeutic use)</term>
<term>Insulin (metabolism)</term>
<term>Insulin-Secreting Cells (drug effects)</term>
<term>Insulin-Secreting Cells (metabolism)</term>
<term>Male (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Peptides (chemistry)</term>
<term>Peptides (therapeutic use)</term>
<term>Petromyzon (MeSH)</term>
<term>Protective Agents (chemistry)</term>
<term>Protective Agents (therapeutic use)</term>
<term>Receptors, Neuropeptide Y (agonists)</term>
<term>Receptors, Neuropeptide Y (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Agents protecteurs (composition chimique)</term>
<term>Agents protecteurs (usage thérapeutique)</term>
<term>Animaux (MeSH)</term>
<term>Cellules à insuline (effets des médicaments et des substances chimiques)</term>
<term>Cellules à insuline (métabolisme)</term>
<term>Diabète expérimental (métabolisme)</term>
<term>Diabète expérimental (prévention et contrôle)</term>
<term>Diabète expérimental (traitement médicamenteux)</term>
<term>Hypoglycémiants (composition chimique)</term>
<term>Hypoglycémiants (usage thérapeutique)</term>
<term>Insuline (métabolisme)</term>
<term>Lignée cellulaire (MeSH)</term>
<term>Mâle (MeSH)</term>
<term>Peptides (composition chimique)</term>
<term>Peptides (usage thérapeutique)</term>
<term>Petromyzon (MeSH)</term>
<term>Protéines de poisson (composition chimique)</term>
<term>Protéines de poisson (usage thérapeutique)</term>
<term>Récepteur neuropeptide Y (agonistes)</term>
<term>Récepteur neuropeptide Y (métabolisme)</term>
<term>Souris (MeSH)</term>
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<term>Hypoglycemic Agents</term>
<term>Peptides</term>
<term>Protective Agents</term>
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<term>Hypoglycémiants</term>
<term>Peptides</term>
<term>Protéines de poisson</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Insulin-Secreting Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Diabetes Mellitus, Experimental</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Cellules à insuline</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Diabetes Mellitus, Experimental</term>
<term>Insulin</term>
<term>Insulin-Secreting Cells</term>
<term>Receptors, Neuropeptide Y</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules à insuline</term>
<term>Diabète expérimental</term>
<term>Insuline</term>
<term>Récepteur neuropeptide Y</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Diabetes Mellitus, Experimental</term>
</keywords>
<keywords scheme="MESH" qualifier="prévention et contrôle" xml:lang="fr"><term>Diabète expérimental</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Fish Proteins</term>
<term>Hypoglycemic Agents</term>
<term>Peptides</term>
<term>Protective Agents</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Diabète expérimental</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Agents protecteurs</term>
<term>Hypoglycémiants</term>
<term>Peptides</term>
<term>Protéines de poisson</term>
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<term>Cell Line</term>
<term>Male</term>
<term>Mice</term>
<term>Petromyzon</term>
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<term>Lignée cellulaire</term>
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<term>Petromyzon</term>
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<front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b>
</p>
<p>PYY (1-36) peptides from phylogenetically ancient fish, such as sea lamprey, have previously been shown to function as specific neuropeptide Y1 receptor (NPYR1) agonists. Although, sea lamprey PYY (1-36) is N-terminally stable, we reveal in this study that the peptide is subject to endopeptidase mediated C-terminal dipeptide degradation. In an attempt to prevent this, (d-Arg</p>
</div>
<div type="abstract" xml:lang="en"><p><b>METHODS</b>
</p>
<p>In vitro bioassays assessed enzymatic stability, insulinostatic activity as well as beta-cell anti-apoptotic actions of (d-Arg</p>
</div>
<div type="abstract" xml:lang="en"><p><b>RESULTS</b>
</p>
<p>(d-Arg</p>
</div>
<div type="abstract" xml:lang="en"><p><b>CONCLUSION</b>
</p>
<p>We present (d-Arg</p>
</div>
<div type="abstract" xml:lang="en"><p><b>GENERAL SIGNIFICANCE</b>
</p>
<p>Enzymatically stable, long-acting PYY (1-36) peptides highlight the therapeutic benefits of sustained activation of NPYR1's in diabetes.</p>
</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32007578</PMID>
<DateCompleted><Year>2020</Year>
<Month>10</Month>
<Day>19</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>10</Month>
<Day>19</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1872-8006</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>1864</Volume>
<Issue>5</Issue>
<PubDate><Year>2020</Year>
<Month>05</Month>
</PubDate>
</JournalIssue>
<Title>Biochimica et biophysica acta. General subjects</Title>
<ISOAbbreviation>Biochim Biophys Acta Gen Subj</ISOAbbreviation>
</Journal>
<ArticleTitle>Development and characterisation of a peptidergic N-and C-terminally stabilised mammalian NPY1R agonist which protects against diabetes induction.</ArticleTitle>
<Pagination><MedlinePgn>129543</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S0304-4165(20)30033-7</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.bbagen.2020.129543</ELocationID>
<Abstract><AbstractText Label="BACKGROUND">PYY (1-36) peptides from phylogenetically ancient fish, such as sea lamprey, have previously been shown to function as specific neuropeptide Y1 receptor (NPYR1) agonists. Although, sea lamprey PYY (1-36) is N-terminally stable, we reveal in this study that the peptide is subject to endopeptidase mediated C-terminal dipeptide degradation. In an attempt to prevent this, (d-Arg<sup>35</sup>
)-sea lamprey PYY (1-36) was developed.</AbstractText>
<AbstractText Label="METHODS">In vitro bioassays assessed enzymatic stability, insulinostatic activity as well as beta-cell anti-apoptotic actions of (d-Arg<sup>35</sup>
)-sea lamprey PYY (1-36). Follow-up studies examined the impact of twice daily administration of sea lamprey PYY (1-36) or (d-Arg<sup>35</sup>
)-sea lamprey PYY (1-36) in multiple low dose STZ-induced diabetic mice.</AbstractText>
<AbstractText Label="RESULTS">(d-Arg<sup>35</sup>
)-sea lamprey PYY (1-36) was fully resistant to plasma enzymatic degradation. The peptide possessed similar significant insulinostatic, as well as positive anti-apoptotic biological actions, as the parent peptide. Sea lamprey PYY (1-36) and (d-Arg<sup>35</sup>
)-sea lamprey PYY (1-36) delayed diabetes progression in STZ mice. Both treatment interventions induced a significant decrease in body weight, food and fluid intake as well as glucose and glucagon concentrations. In addition, glucose tolerance, plasma and pancreatic insulin were partially normalised. (d-Arg<sup>35</sup>
)-sea lamprey PYY (1-36) was significantly more effective than sea lamprey PYY (1-36) in terms of enhancing glucose-stimulate insulin release. Both treatments improved pancreatic islet morphology, linked to decreased apoptosis of beta-cells.</AbstractText>
<AbstractText Label="CONCLUSION">We present (d-Arg<sup>35</sup>
)-sea lamprey PYY (1-36) as the first-in-class N- and C-terminally stable PYY (1-36) peptide analogue.</AbstractText>
<AbstractText Label="GENERAL SIGNIFICANCE">Enzymatically stable, long-acting PYY (1-36) peptides highlight the therapeutic benefits of sustained activation of NPYR1's in diabetes.</AbstractText>
<CopyrightInformation>Copyright © 2020 Elsevier B.V. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lafferty</LastName>
<ForeName>Ryan A</ForeName>
<Initials>RA</Initials>
<AffiliationInfo><Affiliation>SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland BT52 1SA, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tanday</LastName>
<ForeName>Neil</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland BT52 1SA, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Flatt</LastName>
<ForeName>Peter R</ForeName>
<Initials>PR</Initials>
<AffiliationInfo><Affiliation>SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland BT52 1SA, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Irwin</LastName>
<ForeName>Nigel</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland BT52 1SA, UK. Electronic address: n.irwin@ulster.ac.uk.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>01</Month>
<Day>30</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>Netherlands</Country>
<MedlineTA>Biochim Biophys Acta Gen Subj</MedlineTA>
<NlmUniqueID>101731726</NlmUniqueID>
<ISSNLinking>0304-4165</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D029941">Fish Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007004">Hypoglycemic Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007328">Insulin</NameOfSubstance>
</Chemical>
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<NameOfSubstance UI="D010455">Peptides</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D017476">Receptors, Neuropeptide Y</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C097212">neuropeptide Y-Y1 receptor</NameOfSubstance>
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<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003921" MajorTopicYN="N">Diabetes Mellitus, Experimental</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000517" MajorTopicYN="N">prevention & control</QualifierName>
</MeshHeading>
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<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
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<MeshHeading><DescriptorName UI="D007004" MajorTopicYN="N">Hypoglycemic Agents</DescriptorName>
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<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
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<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D050417" MajorTopicYN="N">Insulin-Secreting Cells</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010455" MajorTopicYN="N">Peptides</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D048428" MajorTopicYN="N">Petromyzon</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020011" MajorTopicYN="N">Protective Agents</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017476" MajorTopicYN="N">Receptors, Neuropeptide Y</DescriptorName>
<QualifierName UI="Q000819" MajorTopicYN="Y">agonists</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Beta-cell</Keyword>
<Keyword MajorTopicYN="Y">Diabetes</Keyword>
<Keyword MajorTopicYN="Y">Enzymatic stability</Keyword>
<Keyword MajorTopicYN="Y">Peptide YY (PYY)</Keyword>
<Keyword MajorTopicYN="Y">Sea lamprey</Keyword>
</KeywordList>
<CoiStatement>Declaration of Competing Interest PRF and NI are named on patents filed by the University of Ulster for exploitation of peptide therapeutics.</CoiStatement>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year>
<Month>11</Month>
<Day>25</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2020</Year>
<Month>01</Month>
<Day>27</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2020</Year>
<Month>01</Month>
<Day>28</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2020</Year>
<Month>2</Month>
<Day>3</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2020</Year>
<Month>10</Month>
<Day>21</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2020</Year>
<Month>2</Month>
<Day>3</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">32007578</ArticleId>
<ArticleId IdType="pii">S0304-4165(20)30033-7</ArticleId>
<ArticleId IdType="doi">10.1016/j.bbagen.2020.129543</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Royaume-Uni</li>
</country>
</list>
<tree><country name="Royaume-Uni"><noRegion><name sortKey="Lafferty, Ryan A" sort="Lafferty, Ryan A" uniqKey="Lafferty R" first="Ryan A" last="Lafferty">Ryan A. Lafferty</name>
</noRegion>
<name sortKey="Flatt, Peter R" sort="Flatt, Peter R" uniqKey="Flatt P" first="Peter R" last="Flatt">Peter R. Flatt</name>
<name sortKey="Irwin, Nigel" sort="Irwin, Nigel" uniqKey="Irwin N" first="Nigel" last="Irwin">Nigel Irwin</name>
<name sortKey="Tanday, Neil" sort="Tanday, Neil" uniqKey="Tanday N" first="Neil" last="Tanday">Neil Tanday</name>
</country>
</tree>
</affiliations>
</record>
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