Central administration of an orexin receptor 1 antagonist prevents the stimulatory effect of Olanzapine on endogenous glucose production.
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| Abstract |
Atypical antipsychotic drugs such as Olanzapine (Olan) induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these undesired side-effects are currently unknown. It has been shown that peripheral injections of Olan activate neurons in the lateral hypothalamus/perifornical area and that a large part of these neurons are orexin (Ox) A-positive. We investigated further the possible involvement of the central Ox system in the metabolic side-effects of Olan by comparing the hyperglycaemic effects of an intragastric (IG) Olan infusion between animals treated intracerebroventricularly (ICV) with an Ox-1 receptor antagonist (SB-408124) or vehicle. As observed in previous studies IG Olan caused an increase in blood glucose, endogenous glucose production and plasma glucagon levels. ICV pre-treatment with the Ox-1 receptor antagonist did not affect the Olan-induced hyperglycaemia or increased plasma glucagon concentrations, but the increased endogenous glucose production was blunted by the ICV SB-408124 treatment. From these results we conclude that the metabolic side-effects of Olan are partly mediated by the hypothalamic Ox system.
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| Authors | Elodie M Girault, Ewout Foppen, Mariëtte T Ackermans, Eric Fliers, Andries Kalsbeek |
| Journal | Brain research (Brain Res) Vol. 1527 Pg. 238-45 (Aug 21 2013) ISSN: 1872-6240 [Electronic] Netherlands |
| PMID | 23830851 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2013 Elsevier B.V. All rights reserved. |
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