Insulin-releasing and metabolic effects of small molecule GLP-1 receptor agonist 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline

European Journal of Pharmacology
Nigel IrwinBrian D Green

Abstract

Much recent attention has focused on the GLP-1 receptor as a potential target for antidiabetic drugs. Enzyme resistant GLP-1 mimetics such as exenatide are now employed for the treatment of type 2 diabetes, but must be administered by injection. The present study has examined and compared the in vitro and in vivo metabolic actions of a small molecule GLP-1 receptor agonist 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (DMB), with native GLP-1, exenatide and liraglutide. DMB significantly stimulated in vitro insulin secretion from BRIN-BD11 cells but with decreased molar potency compared to native GLP-1 or related mimetics. Administration of DMB in combination with glucose to mice significantly (P<0.05) decreased the overall glucose excursion compared to controls. Exenatide and liraglutide evoked similar (P<0.001) reductions of the overall glycaemic excursion, but were significantly (P<0.001 and P<0.05; respectively) more effective than DMB. These observations were associated with prominently (P<0.05) enhanced glucose-mediated insulin release by exenatide and liraglutide, but not by DMB. Combined injection of DMB with either liraglutide or exenatide did not substantially improve glucose-lowering or insulin-releasi...Continue Reading

References

Sep 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·B Thorens
Aug 15, 2001·The Journal of Clinical Endocrinology and Metabolism·M B Toft-NielsenJ J Holst
Jan 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Desu ChenMing-Wei Wang
Jan 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Lotte Bjerre KnudsenJesper Lau
May 15, 2007·Gastroenterology·Laurie L Baggio, Daniel J Drucker
Sep 11, 2007·Bioorganic & Medicinal Chemistry Letters·Min TengJesper Lau
Nov 13, 2008·The Journal of Physiology·Gwen TolhurstFiona M Gribble
Mar 12, 2009·Current Drug Metabolism·P R FlattB D Green

❮ Previous
Next ❯

Citations

Dec 24, 2010·American Journal of Physiology. Endocrinology and Metabolism·Jay V PatankarSanja Levak-Frank
May 23, 2012·Experimental Diabetes Research·Francis S WillardKyle W Sloop
Jun 2, 2012·Expert Opinion on Drug Discovery·Kishore Vl Parsa, Manojit Pal
Jun 16, 2011·British Journal of Pharmacology·Jonathan D RothDavid G Parkes
Jan 30, 2013·Biochemical Society Transactions·Cassandra KoolePatrick M Sexton
Dec 3, 2014·Biochemical Pharmacology·Aiysha Thompson, Venkateswarlu Kanamarlapudi
Mar 13, 2012·Pharmacological Reviews·E J Verspohl
Mar 9, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ying LiMin Gong
Sep 29, 2011·British Journal of Pharmacology·Dan Donnelly
Apr 18, 2013·American Journal of Physiology. Endocrinology and Metabolism·Ramya S KunaPrasenjit Mitra
Jul 1, 2014·International Journal of Obesity Supplements·L J MillerK G Harikumar
Jul 27, 2021·Experimental Biology and Medicine·Ying ZhouYang Wang
Oct 29, 2014·Journal of Medicinal Chemistry·Bikash Manandhar, Jung-Mo Ahn
Aug 21, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Josh ReedVenkateswarlu Kanamarlapudi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiovascular Biology of GLP-1

Glucagon-like peptide 1 (GLP-1) plays a role in glucose metabolism, energy homeostasis, and inflammation suppression. GLP-1 receptor signaling has been shown to impact cardiovascular function. This feed focuses on the role of GLP-1 and GLP-1 receptor agonists on cardiovascular biology.