Peptide Co-Agonists for Combined Activation of the APJ and GLP-1 Receptors with Insulinotropic and Satiety Actions Show Potential for Alleviation of Metabolic Dysfunction in Type 2 Diabetes †
Conference paper
Authors | O' Harte, S., Parthsarathy, V., Craig, S., Palmer, E. and Irwin, N. |
---|---|
Type | Conference paper |
Abstract | Stable analogues of the adipokine apelin-13 have shown promising therapeutic potential via APJ receptor activation in isolated β-cells and in animal models of obesity-related diabetes. Incretin mimetics such as exenatide that bind to GLP-1 receptors are well-established Type 2 diabetes treatment options. We developed novel hybrid co-agonist peptide analogues incorporating both exendin-4(1-30) covalently linked to apelin (ELA). The dose-dependent (10−12 to 10−6 M) actions of ELA and component peptides were tested on acute (20 min) insulin secretion from cultured pancreatic BRIN-BD11 β-cells at 5.6 mmol/L glucose. In addition, separate tests were performed in the presence or absence of specific APJ and GLP-1 receptor antagonists. The co-agonist ELA peptide showed markedly greater insulinotropic actions (1.6 to 3.3-fold) than equimolar concentrations of either component peptide alone or in combination (p < 0.001). ELA and related acylated analogues (25 nmol/kg i.p. injection) were also tested on cumulative food intake in trained 21 h-fasted adult mice (n = 8), with food intake measured at 30 min intervals up to 180 min. The ELA co-agonist peptides significantly reduced food intake (3.1-fold by 180 min) in mice (p < 0.001) versus saline-treated controls. ELA peptides showed marked improvements in both insulin secretion and appetite control, raising interest in their therapeutic potential. |
Keywords | apelin; incretin action; diabetes therapy; insulin secretion; hybrid peptides |
Year | 2023 |
Conference | 1st International Meeting Molecules 4 Life |
Journal | Medical Sciences Forum |
Publisher | MDPI |
ISSN | 2673-9992 |
Digital Object Identifier (DOI) | https://doi.org/10.3390/msf2023023001 |
Web address (URL) | https://0-doi-org.brum.beds.ac.uk/10.3390/msf2023023001 |
Publisher's version | License File Access Level Open |
Journal citation | 23 (2), pp. 1-5 |
Output status | Published |
Publication dates | |
Online | 07 Dec 2023 |
Publication process dates | |
Deposited | 15 Jul 2024 |
https://repository.derby.ac.uk/item/q7573/peptide-co-agonists-for-combined-activation-of-the-apj-and-glp-1-receptors-with-insulinotropic-and-satiety-actions-show-potential-for-alleviation-of-metabolic-dysfunction-in-type-2-diabetes
Download files
23
total views2
total downloads0
views this month0
downloads this month