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

Journal article


Parthsarathy, Vadivel, Hogg, Christopher, Flatt, Peter R. and O'Harte, Finbarr P. M. 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. https://doi.org/10.1111/dom.13068
AuthorsParthsarathy, Vadivel, Hogg, Christopher, Flatt, Peter R. and O'Harte, Finbarr P. M.
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.

Keywordsadipokine; apelin analogues; diabetes; obesity; satiety
Year2017
JournalDiabetes Obesity and Metabolism
Journal citation20 (2), pp. 319-327
PublisherWiley
ISSN14628902
Digital Object Identifier (DOI)https://doi.org/10.1111/dom.13068
Web address (URL)http://hdl.handle.net/10545/624633
hdl:10545/624633
http://europepmc.org/article/med/28730728
https://pure.ulster.ac.uk/en/publications/beneficial-long-term-antidiabetic-actions-of-n-and-c-terminally-m-2
http://doi.wiley.com/10.1111/dom.13068
Output statusPublished
Publication dates
Online20 Jul 2017
Publication process dates
Deposited01 Apr 2020
Accepted01 Jul 2017
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Archived with thanks to Diabetes, Obesity and Metabolism

ContributorsUniversity of Ulster, School of Biomedical Sciences, SAAD Centre for Pharmacy and Diabetes; University of Ulster; Coleraine Northern Ireland, UK, School of Biomedical Sciences, SAAD Centre for Pharmacy and Diabetes; University of Ulster; Coleraine Northern Ireland, UK, School of Biomedical Sciences, SAAD Centre for Pharmacy and Diabetes; University of Ulster; Coleraine Northern Ireland, UK and School of Biomedical Sciences, SAAD Centre for Pharmacy and Diabetes; University of Ulster; Coleraine Northern Ireland, UK
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