Glucagon receptor knockout mice are protected against acute olanzapine-induced hyperglycemia

Psychoneuroendocrinology
Laura N CastellaniDavid C Wright

Abstract

To determine if glucagon is involved in mediating the increase in blood glucose levels caused by the second-generation antipsychotic drug olanzapine. Whole body glucagon receptor deficient mice (Gcgr(-/-)) or WT littermate controls were injected with olanzapine (5mg/kg BW IP) and changes in blood glucose measured over the following 120min. Separate cohorts of mice were treated with olanzapine and changes in pyruvate tolerance, insulin tolerance and whole body substrate oxidation were determined. Olanzapine treatment increased serum glucagon and lead to rapid increases in blood glucose concentrations in WT mice. Gcgr(-/-) mice were protected against olanzapine-induced increases in blood glucose but this was not explained by differences in terminal serum insulin concentrations, enhanced AKT phosphorylation in skeletal muscle, adipose tissue or liver or differences in RER. In both genotypes olanzapine induced an equivalent degree of insulin resistance as measured using an insulin tolerance test. Olanzapine treatment led to an exaggerated glucose response to a pyruvate challenge in WT but not Gcgr(-/-) mice and this was paralleled by reductions in the protein content of PEPCK and G6Pase in livers from Gcgr(-/-) mice. Gcgr(-/-) mice...Continue Reading

Citations

Jul 4, 2018·American Journal of Physiology. Endocrinology and Metabolism·Chantel KowalchukMargaret K Hahn
Jan 18, 2018·Scientific Reports·Laura N CastellaniDavid C Wright
Jan 8, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Logan K TownsendDavid C Wright
Jan 30, 2019·Medicine and Science in Sports and Exercise·Willem T PepplerDavid C Wright
Mar 28, 2018·The Journal of Pharmacology and Experimental Therapeutics·Natasha D BushDavid C Wright
Oct 5, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hesham ShamshoumDavid C Wright
Oct 6, 2020·American Journal of Physiology. Endocrinology and Metabolism·Kyle D MedakDavid C Wright
Jan 1, 2021·Journal of Applied Physiology·Hesham ShamshoumDavid C Wright
Feb 17, 2021·Translational Psychiatry·Despoina AslanoglouZachary Freyberg
May 24, 2021·Psychoneuroendocrinology·Jessica W Y YuenAlasdair M Barr

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