PMID- 35052508
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220128
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Dec 21
TI  - Dexamethasone Administration in Mice Leads to Less Body Weight Gain over Time, 
      Lower Serum Glucose, and Higher Insulin Levels Independently of NRF2.
LID - 10.3390/antiox11010004 [doi]
LID - 4
AB  - 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.
FAU - Filippopoulou, Fotini
AU  - Filippopoulou F
AD  - Division of Endocrinology, Department of Internal Medicine, School of Medicine, 
      University of Patras, 26504 Patras, Greece.
FAU - Habeos, George I
AU  - Habeos GI
AD  - Division of Endocrinology, Department of Internal Medicine, School of Medicine, 
      University of Patras, 26504 Patras, Greece.
FAU - Rinotas, Vagelis
AU  - Rinotas V
AD  - Laboratory of Genetics, Department of Biotechnology, Agricultural University of 
      Athens, 11855 Athens, Greece.
AD  - Institute for Bioinnovation, Biomedical Sciences Research Center "Alexander 
      Fleming", 16672 Vari, Greece.
FAU - Sophocleous, Antonia
AU  - Sophocleous A
AD  - Department of Life Sciences, School of Sciences, European University Cyprus, 
      Nicosia 2404, Cyprus.
FAU - Sykiotis, Gerasimos P
AU  - Sykiotis GP
AUID- ORCID: 0000-0002-9565-4941
AD  - Service of Endocrinology, Diabetology and Metabolism, Lausanne University 
      Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
FAU - Douni, Eleni
AU  - Douni E
AD  - Laboratory of Genetics, Department of Biotechnology, Agricultural University of 
      Athens, 11855 Athens, Greece.
AD  - Institute for Bioinnovation, Biomedical Sciences Research Center "Alexander 
      Fleming", 16672 Vari, Greece.
FAU - Chartoumpekis, Dionysios V
AU  - Chartoumpekis DV
AUID- ORCID: 0000-0002-6139-6067
AD  - Division of Endocrinology, Department of Internal Medicine, School of Medicine, 
      University of Patras, 26504 Patras, Greece.
LA  - eng
GR  - IZCOZ0_177070/SNSF_/Swiss National Science Foundation/Switzerland
GR  - CA16112 (NutRedOx)./European Cooperation in Science and Technology/
PT  - Journal Article
DEP - 20211221
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC8773000
OTO - NOTNLM
OT  - KEAP1
OT  - antioxidants
OT  - diabetes
OT  - glucocorticoids
OT  - gluconeogenesis
OT  - insulin resistance
OT  - osteoporosis
COIS- The authors declare no conflict of interest.
EDAT- 2022/01/22 06:00
MHDA- 2022/01/22 06:01
PMCR- 2021/12/21
CRDT- 2022/01/21 01:03
PHST- 2021/12/06 00:00 [received]
PHST- 2021/12/17 00:00 [revised]
PHST- 2021/12/19 00:00 [accepted]
PHST- 2022/01/21 01:03 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/01/22 06:01 [medline]
PHST- 2021/12/21 00:00 [pmc-release]
AID - antiox11010004 [pii]
AID - antioxidants-11-00004 [pii]
AID - 10.3390/antiox11010004 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2021 Dec 21;11(1):4. doi: 10.3390/antiox11010004.