Dexamethasone Administration in Mice Leads to Less Body Weight Gain over Time, Lower Serum Glucose, and Higher Insulin Levels Independently of NRF2.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_2BFF57D4A6C3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dexamethasone Administration in Mice Leads to Less Body Weight Gain over Time, Lower Serum Glucose, and Higher Insulin Levels Independently of NRF2.
Journal
Antioxidants
Author(s)
Filippopoulou F., Habeos G.I., Rinotas V., Sophocleous A., Sykiotis G.P., Douni E., Chartoumpekis D.V.
ISSN
2076-3921 (Print)
ISSN-L
2076-3921
Publication state
Published
Issued date
21/12/2021
Peer-reviewed
Oui
Volume
11
Number
1
Pages
4
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Glucocorticoids are used widely on a long-term basis in autoimmune and inflammatory diseases. Their adverse effects include the development of hyperglycemia and osteoporosis, whose molecular mechanisms have been only partially studied in preclinical models. Both these glucocorticoid-induced pathologies have been shown to be mediated at least in part by oxidative stress. The transcription factor nuclear erythroid factor 2-like 2 (NRF2) is a central regulator of antioxidant and cytoprotective responses. Thus, we hypothesized that NRF2 may play a role in glucocorticoid-induced metabolic disease and osteoporosis. To this end, WT and Nrf2 knockout (Nrf2KO) mice of both genders were treated with 2 mg/kg dexamethasone or vehicle 3 times per week for 13 weeks. Dexamethasone treatment led to less weight gain during the treatment period without affecting food consumption, as well as to lower glucose levels and high insulin levels compared to vehicle-treated mice. Dexamethasone also reduced cortical bone volume and density. All these effects of dexamethasone were similar between male and female mice, as well as between WT and Nrf2KO mice. Hepatic NRF2 signaling and gluconeogenic gene expression were not affected by dexamethasone. A 2-day dexamethasone treatment was also sufficient to increase insulin levels without affecting body weight and glucose levels. Hence, dexamethasone induces hyperinsulinemia, which potentially leads to decreased glucose levels, as well as osteoporosis, both independently of NRF2.
Keywords
KEAP1, antioxidants, diabetes, glucocorticoids, gluconeogenesis, insulin resistance, osteoporosis
Pubmed
Web of science
Open Access
Yes
Create date
31/01/2022 11:43
Last modification date
03/10/2023 21:40
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