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    Beneficial long-term antidiabetic actions of N- and C-terminally modified analogues of apelin-13 in diet-induced obese diabetic mice

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    Authors
    Parthsarathy, Vadivel
    Hogg, Christopher
    Flatt, Peter R.
    O'Harte, Finbarr P. M.
    Affiliation
    University of Ulster
    Issue Date
    2017-07-20
    
    Metadata
    Show full item record
    Abstract
    To investigate the chronic effects of twice-daily administration of stable apelin analogues, apelin-13 amide and pyroglutamyl (pGlu) apelin-13 amide, on metabolic variables in glucose-intolerant and insulin-resistant diet-induced obese mice fed a high-fat diet for 150 days. Groups of mice received twice-daily (9 am and 5 pm) injections of saline vehicle, apelin-13 amide, (pGlu)apelin-13 amide or exendin-4(1-39) for 28 days (all at 25 nmol/kg). Energy intake, body weight, non-fasting blood glucose, plasma insulin, glucose tolerance, metabolic response to feeding and insulin sensitivity, together with pancreatic hormone content and biochemical variables such as lipids and total GLP-1 were monitored. Dual-energy X-ray absorptiometry analysis and indirect calorimetry were also performed. Administration of apelin-13 amide, (pGlu)apelin-13 amide or exendin-4 significantly decreased body weight, food intake and blood glucose and increased plasma insulin compared with high-fat-fed saline-treated controls (P < .05 and P < .001), Additionally, all peptide-treated groups exhibited improved glucose tolerance (oral and intraperitoneal), metabolic responses to feeding and associated insulin secretion. (pGlu)apelin-13 amide also significantly improved glycated haemoglobin and insulin sensitivity after 28 days. Both (pGlu)apelin-13 amide and exendin-4 increased bone mineral content and decreased respiratory exchange ratio, whereas only (pGlu)apelin-13 amide increased energy expenditure. All treatment groups displayed reduced circulating triglycerides and increased glucagon-like peptide-1 concentrations, although only (pGlu)apelin-13 amide significantly reduced LDL cholesterol and total body fat, and increased pancreatic insulin content. These data indicate the therapeutic potential of stable apelin-13 analogues, with effects equivalent to or better than those of exendin-4.
    Citation
    Parthsarathy, V., Hogg, C., Flatt, P., and O'Harte, F. (2017). 'Beneficial long-term antidiabetic actions of N- and C-terminally modified analogues of apelin-13 in diet-induced obese diabetic mice'. Diabetes Obesity and Metabolism, 20 (2). pp. 319-327.
    Publisher
    Wiley
    Journal
    Diabetes, Obesity and Metabolism
    URI
    http://hdl.handle.net/10545/624633
    DOI
    10.1111/dom.13068
    Additional Links
    http://doi.wiley.com/10.1111/dom.13068
    http://uir.ulster.ac.uk/38387/
    Type
    Article
    Language
    en
    ISSN
    14628902
    ae974a485f413a2113503eed53cd6c53
    10.1111/dom.13068
    Scopus Count
    Collections
    Human Sciences Research Centre

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