Xenin-25[Lys(13)PAL]: a novel long-acting acylated analogue of xenin-25 with promising antidiabetic potential
Journal article
Authors | Gault, Victor A., Martin, Christine M., Flatt, Peter R., Parthsarathy, Vadivel and Irwin, Nigel |
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Abstract | AIMS: Xenin-25 is co-secreted with glucose-dependent insulinotropic polypeptide (GIP) from intestinal K-cells following a meal. Xenin-25 is believed to play a key role in glucose homoeostasis and potentiate the insulinotropic effect of GIP. METHODS: This study investigated the effects of sub-chronic administration of the stable and longer-acting xenin-25 analogue, xenin-25[Lys(13)PAL] (25 nmol/kg), in diabetic mice fed with a high-fat diet. RESULTS: Initial studies confirmed the significant persistent glucose-lowering (p < 0.05) and insulin-releasing (p < 0.05) actions of xenin-25[Lys(13)PAL] compared with native xenin-25. Interestingly, xenin-25 retained significant glucose-lowering activity in GIP receptor knockout mice. Twice-daily intraperitoneal (i.p.) injection of xenin-25[Lys(13)PAL] for 14 days had no significant effect on food intake or body weight in high-fat-fed mice. Non-fasting glucose and insulin levels were also unchanged, but overall glucose levels during an i.p. glucose tolerance and oral nutrient challenge were significantly (p < 0.05) lowered by xenin-25[Lys(13)PAL] treatment. These changes were accompanied by significant improvements in i.p. (p < 0.05) and oral (p < 0.001) nutrient-stimulated insulin concentrations. No appreciable changes in insulin sensitivity were observed between xenin-25[Lys(13)PAL] and saline-treated high-fat mice. However, xenin-25[Lys(13)PAL] treatment restored notable sensitivity to the biological actions of exogenous GIP injection. Consumption of O2, production of CO2, respiratory exchange ratio and energy expenditure were not altered by 14-day twice-daily treatment with xenin-25[Lys(13)PAL]. In contrast, ambulatory activity was significantly (p < 0.05 to p < 0.001) increased during the dark phase in xenin-25[Lys(13)PAL] mice compared with high-fat controls. |
Keywords | diabetes; obesity; glucose |
Year | 2015 |
Journal | Acta Diabetologica |
Journal citation | 52 (3), pp. 461-471 |
Publisher | Springer |
ISSN | 0940-5429 |
1432-5233 | |
Digital Object Identifier (DOI) | https://doi.org/10.1007/s00592-014-0681-0 |
Web address (URL) | http://hdl.handle.net/10545/622909 |
hdl:10545/622909 | |
http://europepmc.org/article/med/25374384 | |
Output status | Published |
Publication dates | 06 Nov 2014 |
Publication process dates | |
Deposited | 16 Aug 2018 |
https://repository.derby.ac.uk/item/92z57/xenin-25-lys-13-pal-a-novel-long-acting-acylated-analogue-of-xenin-25-with-promising-antidiabetic-potential
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