Degradation, insulin secretion, glucose-lowering and GIP additive actions of a palmitate-derivatised analogue of xenin-25

Biochemical Pharmacology
Christine M A MartinNigel Irwin

Abstract

Xenin-25, a K-cell derived peptide co-secreted with glucose-dependent insulinotropic polypeptide (GIP), has recently been shown to have glucose homeostatic actions and potentiate the insulinotropic effect of GIP. However, the biological actions of xenin-25 are brief due to rapid metabolism, yet little is known regarding enzymatic degradation of this peptide. Therefore, the present study has fully characterised the plasma enzymatic degradation products of xenin-25. We have also generated a novel acylated xenin-25 analogue, xenin-25(Lys(13)PAL), and evaluated its stability, biological action profile and therapeutic applicability compared to the native peptide. In contrast to xenin-25, xenin-25(Lys(13)PAL) was completely resistant to plasma enzyme degradation. Insulinotropic responses of xenin-25(Lys(13)PAL) in clonal beta-cells were similar to native xenin-25, moreover xenin-25(Lys(13)PAL) significantly (p<0.05 to p<0.001) potentiated the insulin releasing action of (D-Ala(2))GIP. When administered together with glucose to normal mice, the glycaemic excursion was significantly (p<0.05) less and overall insulin secretory effect significantly (p<0.05) greater for xenin-25(Lys(13)PAL) when compared to xenin-25 mice. Glucose-lowering...Continue Reading

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Citations

Oct 23, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sheng ZhangBurton M Wice
Feb 13, 2014·The Journal of Endocrinology·Christine M A MartinNigel Irwin
Jan 24, 2016·Biochimica Et Biophysica Acta·Vadivel ParthsarathyVictor A Gault
Apr 14, 2016·Naunyn-Schmiedeberg's Archives of Pharmacology·Bosede O OwolabiYasser H A Abdel-Wahab
Sep 26, 2013·Current Opinion in Pharmacology·Nigel Irwin, Peter R Flatt
May 4, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Eri IkeguchiNobuya Inagaki
Apr 11, 2018·Diabetes/metabolism Research and Reviews·Sarah L CraigNigel Irwin
Dec 21, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sara ChowdhuryBurton M Wice
Feb 29, 2020·Clinical Medicine Insights. Endocrinology and Diabetes·Annie Hasib
Aug 17, 2020·Domestic Animal Endocrinology·T OnagaH Hayashi
Jul 22, 2018·European Journal of Pharmacology·Annie HasibNigel Irwin
Jun 11, 2021·Domestic Animal Endocrinology·Takenori OnagaYumiko Yasui
Jun 8, 2021·Frontiers in Endocrinology·Ryan A LaffertyPeter R Flatt

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