PMID- 32635208
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240329
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 9
IP  - 7
DP  - 2020 Jul 3
TI  - Supplementation of 17beta-Estradiol Normalizes Rapid Gastric Emptying by Restoring 
      Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice.
LID - 10.3390/antiox9070582 [doi]
LID - 582
AB  - Gastroparesis (Gp) is a multifactorial condition commonly observed in females and 
      is characterized by delayed or rapid gastric emptying (GE). The role of ovarian 
      hormones on GE in the pathogenesis of obesity induced type 2 diabetes mellitus 
      (T2DM) is completely unknown. The aims of our study are to investigate whether 
      supplementation of 17beta-estradiol (E(2)) or progesterone (P(4)) restores impaired 
      nuclear factor erythroid 2-related factor 2 (Nrf2, an oxidative stress-responsive 
      transcription factor) and nitric oxide (NO)-mediated gastric motility in 
      ovariectomized (OVX) mice consuming a high-fat diet (HFD, a model of T2DM). 
      Groups of OVX+HFD mice were administered daily subcutaneous doses of either E(2) 
      or P(4) for 12 weeks. The effects of E(2) and P(4) on body weight, metabolic 
      homeostasis, solid GE, gastric antrum NO-mediated relaxation, total nitrite 
      levels, neuronal nitric oxide synthase (nNOSalpha), and its cofactor expression 
      levels were assessed in OVX+HFD mice. HFD exacerbated hyperglycemia and 
      insulinemia while accelerating GE (p < 0.05) in OVX mice. Exogenous E(2), but not 
      P(4), attenuated rapid gastric emptying and restored gastric nitrergic 
      relaxation, total nitrite levels, nNOSalpha, and cofactor expression via normalizing 
      Nrf2-Phase II enzymes, inflammatory response, and mitogen-activated protein 
      kinase (MAPK) protein expression in OVX+HFD mice. We conclude that E(2) is 
      beneficial in normalizing metabolic homeostasis and gastric emptying in obese, 
      diabetic OVX mice consuming a fat-rich diet.
FAU - Sprouse, Jeremy C
AU  - Sprouse JC
AD  - School of Graduate Studies, Meharry Medical College, Nashville, TN 37208, USA.
FAU - Sampath, Chethan
AU  - Sampath C
AD  - Department of ODS & Research, School of Dentistry, Nashville, TN 37208, USA.
FAU - Gangula, Pandu R
AU  - Gangula PR
AUID- ORCID: 0000-0001-7259-570X
AD  - Department of ODS & Research, School of Dentistry, Nashville, TN 37208, USA.
LA  - eng
GR  - SC1 GM121282/GM/NIGMS NIH HHS/United States
GR  - U54 MD007593/MD/NIMHD NIH HHS/United States
GR  - SC1GM121282/GM/NIGMS NIH HHS/United States
GR  - U54MD007586/MD/NIMHD NIH HHS/United States
PT  - Journal Article
DEP - 20200703
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC7402187
OTO - NOTNLM
OT  - Nrf2
OT  - antioxidants
OT  - cytokines
OT  - diabetes
OT  - estrogen
OT  - gastroparesis
OT  - nNOS
OT  - obesity
OT  - progesterone
COIS- The authors declare no conflict of interest.
EDAT- 2020/07/09 06:00
MHDA- 2020/07/09 06:01
PMCR- 2020/07/03
CRDT- 2020/07/09 06:00
PHST- 2020/06/15 00:00 [received]
PHST- 2020/06/25 00:00 [revised]
PHST- 2020/07/01 00:00 [accepted]
PHST- 2020/07/09 06:00 [entrez]
PHST- 2020/07/09 06:00 [pubmed]
PHST- 2020/07/09 06:01 [medline]
PHST- 2020/07/03 00:00 [pmc-release]
AID - antiox9070582 [pii]
AID - antioxidants-09-00582 [pii]
AID - 10.3390/antiox9070582 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2020 Jul 3;9(7):582. doi: 10.3390/antiox9070582.