Absence of cannabinoid 1 receptor in beta cells protects against high-fat/high-sugar diet-induced beta cell dysfunction and inflammation in murine islets

Diabetologia
Isabel González-MariscalJosephine M Egan

Abstract

The cannabinoid 1 receptor (CB1R) regulates insulin sensitivity and glucose metabolism in peripheral tissues. CB1R is expressed on pancreatic beta cells and is coupled to the G protein Gαi, suggesting a negative regulation of endogenous signalling in the beta cell. Deciphering the exact function of CB1R in beta cells has been confounded by the expression of this receptor on multiple tissues involved in regulating metabolism. Thus, in models of global genetic or pharmacological CB1R blockade, it is difficult to distinguish the indirect effects of improved insulin sensitivity in peripheral tissues from the direct effects of inhibiting CB1R in beta cells per se. To assess the direct contribution of beta cell CB1R to metabolism, we designed a mouse model that allows us to determine the role of CB1R specifically in beta cells in the context of whole-body metabolism. We generated a beta cell specific Cnr1 (CB1R) knockout mouse (β-CB1R-/-) to study the long-term consequences of CB1R ablation on beta cell function in adult mice. We measured beta cell function, proliferation and viability in these mice in response to a high-fat/high-sugar diet and induction of acute insulin resistance with the insulin receptor antagonist S961. β-CB1R-/-...Continue Reading

References

May 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·K Mackie, B Hille
Jan 1, 1989·Developmental Genetics·S L MarbanJ D Gearhart
Dec 8, 1973·Lancet·K G AlbertiH Orskov
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·A ZimmerT I Bonner
Apr 23, 2003·The Journal of Molecular Diagnostics : JMD·Chris CheadleKevin G Becker
Feb 11, 2004·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·C Ravinet TrillouP Soubrié
Dec 20, 2007·Diabetologia·F J Bermúdez-SilvaF Rodríguez de Fonseca
May 9, 2008·Journal of Neuroendocrinology·S Engeli
Dec 17, 2008·Pharmacological Reviews·Wook Kim, Josephine M Egan
Mar 17, 2009·Best Practice & Research. Clinical Endocrinology & Metabolism·Francisco J Bermúdez-SilvaFernando Rodríguez de Fonseca
Jun 30, 2009·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ruben NogueirasMatthias H Tschöp
Oct 21, 2009·CNS & Neurological Disorders Drug Targets·George D DaltonAllyn C Howlett
Dec 22, 2009·Nature Immunology·Rongbin ZhouJürg Tschopp
Feb 24, 2010·Molecular and Cellular Endocrinology·Hwanju CheonMyung-Shik Lee
Mar 30, 2010·Pharmacology, Biochemistry, and Behavior·F J Bermudez-SilvaF Rodriguez de Fonseca
Jan 11, 2011·Nature Medicine·Bolormaa VandanmagsarVishwa Deep Dixit
Feb 25, 2011·Diabetes·Wook KimJosephine M Egan
Sep 3, 2011·The Journal of Endocrinology·Silvana Y Romero-ZerboFrancisco J Bermúdez-Silva
May 23, 2012·Biochemical and Biophysical Research Communications·Charles E SpivakMáire E Doyle
Jan 8, 2013·Frontiers in Physiology·Hongyu ChenStuart Maudsley
Jun 21, 2013·Diabetes, Obesity & Metabolism·L O'KeefeA J McAinch
Jul 9, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Resat CinarGeorge Kunos
Oct 4, 2013·The Journal of Biological Chemistry·Katarzyna MalenczykAgnieszka Dobrzyn
Dec 18, 2013·Women's Health·Brigid K Killelea, Cary P Gross
Dec 18, 2013·The Journal of Biological Chemistry·Zachary T KelleherHarvey E Marshall
Feb 5, 2014·Immunology and Cell Biology·Clara Westwell-RoperJan A Ehses
Feb 15, 2014·Nature Reviews. Drug Discovery·Amedeo VetereBridget K Wagner
Apr 18, 2014·The Journal of Endocrinology·Xuefeng YangWenhong Cao
Mar 23, 2015·Trends in Pharmacological Sciences·Mauro MaccarroneAndreas Zimmer
May 23, 2015·Diabetes·Andrew F StewartRohit N Kulkarni
Aug 14, 2015·Brain Pathology·Cara J ValvonaGeoffrey J Pilkington
Oct 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Katarzyna MalenczykTibor Harkany
Nov 27, 2015·The Journal of Physiology·Guillermo López-Lluch, Plácido Navas
Jan 3, 2016·Molecular and Cellular Endocrinology·Isabel González-MariscalJosephine M Egan
Sep 20, 2016·Scientific Reports·Isabel González-MariscalJosephine M Egan
Nov 9, 2016·Frontiers in Physiology·Juan Mendizabal-ZubiagaPedro Grandes

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Citations

Apr 11, 2018·American Journal of Physiology. Endocrinology and Metabolism·Isabel González-Mariscal, Josephine M Egan
Feb 7, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Isabel González-MariscalJosephine M Egan
Feb 20, 2020·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Medha PriyadarshiniBrian T Layden
Oct 26, 2018·Journal of Translational Medicine·Lin WangTao Cai
Oct 26, 2018·Circulation Research·Chee W ChiaLuigi Ferrucci
May 1, 2019·International Journal of Molecular Sciences·Arulkumar NagappanMyeong Ho Jung
Jul 10, 2019·Frontiers in Physiology·Donovan A ArguetaNicholas V DiPatrizio
May 6, 2020·International Journal of Molecular Sciences·Juliane ZibolkaIvonne Bazwinsky-Wutschke
Nov 8, 2020·Disease Models & Mechanisms·Urmas RoostaluJacob Hecksher-Sørensen
Nov 5, 2020·Cell Chemical Biology·Aurélien LaguerreCarsten Schultz
Feb 16, 2021·Frontiers in Immunology·Santosh V SuryavanshiOlga Kovalchuk
Jan 12, 2020·Pharmacology & Therapeutics·Resat CinarGeorge Kunos
Dec 30, 2020·International Journal of Molecular Sciences·Qing-Rong LiuEmmanuel S Onaivi
Mar 15, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ji Hye Han, Wook Kim
Apr 4, 2021·Cells·Inmaculada Ruz-MaldonadoShanta J Persaud
May 22, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Isabel González-MariscalEduardo Muñoz
Jun 14, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gerwyn MorrisAndre F Carvalho
Aug 24, 2021·Journal of Inflammation Research·Mansour Haddad

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Methods Mentioned

BETA
NMR
ELISA

Software Mentioned

ImageJ
BD FACSDiva

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