• Login
    View Item 
    •   Home
    • Research Publications
    • Research Centres & Groups
    • Environmental Sustainability Research Centre
    • View Item
    •   Home
    • Research Publications
    • Research Centres & Groups
    • Environmental Sustainability Research Centre
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UDORACommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    About and further information

    AboutOpen Access WebpagesOpen Access PolicyTake Down Policy University Privacy NoticeUniversity NewsTools for ResearchersLibraryUDo

    Statistics

    Display statistics

    An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Hasib, Annie
    Ng, Tony
    Gault, Victor A.
    Khan, Dawood
    Parthsarathy, Vadivel cc
    Flatt, Peter
    Irwin, Nigel
    Issue Date
    2017-03-01
    
    Metadata
    Show full item record
    Abstract
    AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) and xenin, regulatory gut hormones secreted from enteroendocrine K cells, exert important effects on metabolism. In addition, xenin potentiates the biological actions of GIP. The present study assessed the actions and therapeutic utility of a (DAla2)GIP/xenin-8-Gln hybrid peptide, in comparison with the parent peptides (DAla2)GIP and xenin-8-Gln.METHODS: Following confirmation of enzymatic stability, insulin secretory activity of (DAla2)GIP/xenin-8-Gln was assessed in BRIN-BD11 beta cells. Acute and persistent glucose-lowering and insulin-releasing effects were then examined in vivo. Finally, the metabolic benefits of twice daily injection of (DAla2)GIP/xenin-8-Gln was determined in high-fat-fed mice.RESULTS: All peptides significantly (p < 0.05 to p < 0.001) enhanced in vitro insulin secretion from pancreatic clonal BRIN-BD11 cells, with xenin (and particularly GIP)-related signalling pathways, being important for this action. Administration of (DAla2)GIP or (DAla2)GIP/xenin-8-Gln in combination with glucose significantly (p < 0.05) lowered blood glucose and increased plasma insulin in mice, with a protracted response of up to 4 h. All treatments elicited appetite-suppressive effects (p < 0.05), particularly (DAla2)GIP/xenin-8-Gln and xenin-8-Gln at elevated doses of 250 nmol/kg. Twice-daily administration of (DAla2)GIP/xenin-8-Gln or (DAla2)GIP for 21 days to high-fat-fed mice returned circulating blood glucose to lean control levels. In addition, (DAla2)GIP/xenin-8-Gln treatment significantly (p < 0.05) reduced glycaemic levels during a 24 h glucose profile assessment. Neither of the treatment regimens had an effect on body weight, energy intake or circulating insulin concentrations. However, insulin sensitivity was significantly (p < 0.001) improved by both treatments. Interestingly, GIP-mediated glucose-lowering (p < 0.05) and insulin-releasing (p < 0.05 to p < 0.01) effects were substantially improved by (DAla2)GIP and (DAla2)GIP/xenin-8-Gln treatment. Pancreatic islet and beta cell area (p < 0.001), as well as pancreatic insulin content (p < 0.05), were augmented in (DAla2)GIP/xenin-8-Gln-treated mice, related to enhanced proliferation and decreased apoptosis of beta cells, whereas (DAla2)GIP evoked increases (p < 0.05 to p < 0.01) in islet number.CONCLUSIONS/INTERPRETATION: These studies highlight the clear potential of GIP/xenin hybrids for the treatment of type 2 diabetes.
    Citation
    Hasib, Annie, Ng, Tony, Gault, Victor A, Khan, Dawood, Parthsarathy, Vadivel, Flatt, Peter and Irwin, Nigel (2017) An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice. Diabetologia, 60 (3). pp. 541-552.
    Publisher
    Springer
    Journal
    Diabetologia
    URI
    http://hdl.handle.net/10545/622902
    DOI
    10.1007/s00125-016-4186-y
    Additional Links
    http://uir.ulster.ac.uk/36833/
    Type
    Journal article
    ISSN
    0012-186X
    ae974a485f413a2113503eed53cd6c53
    10.1007/s00125-016-4186-y
    Scopus Count
    Collections
    Environmental Sustainability Research Centre

    entitlement

     
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.