Characterisation and antidiabetic utility of a novel hybrid peptide, exendin-4/gastrin/xenin-8-Gln

European Journal of Pharmacology
Annie HasibN Irwin

Abstract

Enteroendocrine derived hormones such as glucagon-like-peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), gastrin and xenin are known to exert complementary beneficial metabolic effects in diabetes. This study has assessed the biological activity and therapeutic utility of a novel GLP-1/gastrin/xenin hybrid peptide, namely exendin-4/gastrin/xenin-8-Gln hybrid, both alone and in combination with the stable GIP mimetic, (DAla2)GIP. Exendin-4/gastrin/xenin-8-Gln increased in vitro insulin secretion to a similar or superior extent, as the parent peptides. Insulinotropic effects were mainly linked to modulation of GLP-1 and neurotensin receptors. Exendin-4/gastrin/xenin-8-Gln also augmented the insulinotropic actions of (DAla2)GIP. Acute administration of exendin-4/gastrin/xenin-8-Gln in mice induced significant appetite suppressive, glucose lowering and insulin secretory effects, with a duration of biological action beyond 8 h. Twice daily administration of exendin-4, exendin-4/gastrin/xenin-8-Gln, either alone or in combination with (DAla2)GIP, reduced circulating glucose, increased plasma insulin as well as improving glucose tolerance, insulin sensitivity and metabolic response to GIP in high fat fed mice. Bod...Continue Reading

References

Aug 1, 1998·Brain Research·C AlexiouV Schusdziarra
Jun 19, 2001·American Journal of Physiology. Endocrinology and Metabolism·C M EdwardsS R Bloom
Jul 23, 2003·Regulatory Peptides·Ramona A SilvestreJosé Marco
Jan 25, 2008·The Journal of Biological Chemistry·Zhengyu Liu, Joel F Habener
Jan 29, 2008·Pediatric Diabetes·Rebecca J Brown, Kristina I Rother
Mar 12, 2009·Current Drug Metabolism·P R FlattB D Green
Apr 28, 2010·The Journal of Biological Chemistry·Burton M WiceKenneth S Polonsky
Jul 6, 2010·Neuroscience Letters·Eun Ran Kim, Tooru M Mizuno
Sep 29, 2011·British Journal of Pharmacology·Dan Donnelly
Feb 2, 2013·Current Diabetes Reports·Kathleen A Page, Tamar Reisman
Mar 23, 2013·Biochimica Et Biophysica Acta·Christine M A MartinVictor A Gault
May 21, 2013·Cell Metabolism·Jonathan E Campbell, Daniel J Drucker
Jan 2, 2014·Therapeutic Advances in Chronic Disease·Rachel C TrokeSteve R Bloom
Jan 16, 2014·The Journal of Clinical Endocrinology and Metabolism·Mikkel B ChristensenFilip K Knop
May 8, 2014·Cardiovascular & Hematological Disorders Drug Targets·Sarah FarrKhosrow Adeli
May 21, 2014·Journal of Diabetes Investigation·Mitsuhisa KomatsuYoshihiko Sato
Jun 7, 2014·The Journal of Pharmacology and Experimental Therapeutics·Louise S DalbøgeKeld Fosgerau

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Citations

Jun 19, 2019·Current Medical Science·Chao WangKun Huang
May 20, 2020·Clinical Medicine Insights. Endocrinology and Diabetes·Andrew English, Nigel Irwin
Feb 29, 2020·Clinical Medicine Insights. Endocrinology and Diabetes·Annie Hasib
Nov 27, 2019·Molecular Metabolism·T D MüllerM H Tschöp
Jun 8, 2021·Frontiers in Endocrinology·Ryan A LaffertyPeter R Flatt

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