Chronic apelin analogue administration is more effective than established incretin therapies for alleviating metabolic dysfunction in diabetic db/db mice
Journal article
O'Harte, Finbarr P M, Parthsarathy, Vadivel and Flatt, Peter R 2020. Chronic apelin analogue administration is more effective than established incretin therapies for alleviating metabolic dysfunction in diabetic db/db mice. Molecular and cellular endocrinology. 504, p. 110695. https://doi.org/10.1016/j.mce.2019.110695
| Authors | O'Harte, Finbarr P M, Parthsarathy, Vadivel and Flatt, Peter R |
|---|---|
| Abstract | Stable apelin-13 peptide analogues have shown promising acute antidiabetic effects in mice with diet-induced obesity diabetes. Here the efficacy of (pGlu)apelin-13 amide (apelin amide) and the acylated analogue (pGlu)(Lys8GluPAL)apelin-13 amide (apelin FA), were examined following chronic administration in db/db mice, a genetic model of degenerative diabetes. Groups of 9-week old male db/db mice (n = 8) received twice daily injections (09:00 and 17:00 h; i.p.) or saline vehicle, apelin amide, apelin FA, or the established incretin therapies, exendin-4(1-39) or liraglutide, all at 25 nmol/kg body weight for 21 days. Control C57BL/6J mice were given saline twice daily. No changes in body weight or food intake were observed with either apelin or liraglutide treatments, but exendin-4 showed a reduction in cumulative food intake (p < 0.01) compared with saline-treated db/db mice. Apelin analogues and incretin mimetics induced sustained improvements of glycaemia (p < 0.05 to p < 0.001, from day 9-21), lowered HbA1c at 21 days (p < 0.05) and raised plasma insulin concentrations. The treatments also improved OGTT and ipGTT with enhanced insulin responses compared with saline-treated control db/db mice (p < 0.05 to p < 0.001). Apelin amide was superior to incretin mimetics in lowering plasma triglycerides by 34% (p < 0.05). Apelin analogues unlike both incretin mimetics reduced pancreatic α-cell area (p < 0.05 to p < 0.01) and all peptide treatments enhanced pancreatic insulin content (p < 0.05 to p < 0.01). In conclusion, longer-term administration of apelin-13 analogues, induced similar and in some respects more effective metabolic improvements than incretin mimetics in db/db mice, providing a viable alternative approach for counteracting metabolic dysfunction for mild and more degenerative forms of the disease. |
| Keywords | Apelin analogues; Diabetes; Incretin mimetics; Pancreas; Therapy; db/db mice |
| Year | 2020 |
| Journal | Molecular and cellular endocrinology |
| Journal citation | 504, p. 110695 |
| Publisher | Elsevier |
| ISSN | 1872-8057 |
| Digital Object Identifier (DOI) | https://doi.org/10.1016/j.mce.2019.110695 |
| Web address (URL) | https://www.sciencedirect.com/science/article/abs/pii/S0303720719303971 |
| http://europepmc.org/article/med/31904406 | |
| https://pure.ulster.ac.uk/en/publications/chronic-apelin-analogue-administration-is-more-effective-than-est | |
| http://hdl.handle.net/10545/624636 | |
| hdl:10545/624636 | |
| Output status | Published |
| Publication dates | 03 Jan 2020 |
| Publication process dates | |
| Deposited | 01 Apr 2020 |
| Accepted | 27 Dec 2019 |
| Rights | Copyright © 2020 Elsevier B.V. All rights reserved. |
| Contributors | University of Ulster |
| Place of publication | Ireland |
| File | File Access Level Open |
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