PMID- 28973666
OWN - NLM
STAT- MEDLINE
DCOM- 20180625
LR  - 20180625
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 160
IP  - 1
DP  - 2017 Nov 1
TI  - Exposure of Pregnant Mice to Triclosan Causes Insulin Resistance via Thyroxine 
      Reduction.
PG  - 150-160
LID - 10.1093/toxsci/kfx166 [doi]
AB  - Exposure to triclosan (TCS), an antibacterial agent, during pregnancy is 
      associated with hypothyroxinemia and decreases in placental glucose transporter 
      expression and activity. The objective of this study was to investigate the 
      influence of TCS on glucose homeostasis and insulin sensitivity in gestational 
      mice (G-mice) and nongestational female mice (Ng-mice) as a control. Herein, we 
      show that the exposure of G-mice to TCS (8 mg/kg) from gestational day (GD) 5 to 
      GD17 significantly increased their levels of fasting plasma glucose and serum 
      insulin, and insulin content in pancreatic beta-cells with reduced homeostasis model 
      assessment (HOMA)-beta index and increased HOMA-IR index. Area under curve (AUC) of 
      glucose and insulin tolerance tests in TCS (8 mg/kg)-treated G-mice were markedly 
      larger than controls. When compared with controls, TCS (8 mg/kg)-treated G-mice 
      showed a significant decrease in the levels of thyroxine and 
      triiodothyroninelevels, PPARgamma and glucose transporter 4 (GLUT4) expression, and 
      Akt phosphorylation in adipose tissue and muscle. Replacement of L-thyroxine in 
      TCS (8 mg/kg)-treated G-mice corrected their insulin resistance and recovered the 
      levels of insulin, PPARgamma and GLUT4 expression, and Akt phosphorylation. 
      Activation of PPARgamma by administration of rosiglitazone recovered the decrease in 
      Akt phosphorylation, but not GLUT4 expression. Although exposure to TCS (8 mg/kg) 
      in Ng-mice reduced thyroid hormones levels, it did not cause the insulin 
      resistance or affect PPARgamma and GLUT4 expression, and Akt phosphorylation. The 
      findings indicate that the exposure of gestational mice to TCS (>/=8 mg/kg) results 
      in insulin resistance via thyroid hormones reduction.
CI  - (c) The Author 2017. Published by Oxford University Press on behalf of the Society 
      of Toxicology. All rights reserved. For Permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Hua, Xu
AU  - Hua X
AD  - State Key Laboratory of Reproductive Medicine.
AD  - Department of Physiology.
FAU - Cao, Xin-Yuan
AU  - Cao XY
AD  - Department of Physiology.
FAU - Wang, Xiao-Li
AU  - Wang XL
AD  - Department of Physiology.
FAU - Sun, Peng
AU  - Sun P
AD  - Department of Biochemistry and Molecular Biology, Nanjing Medical University, 
      Nanjing 211166, China.
FAU - Chen, Ling
AU  - Chen L
AD  - State Key Laboratory of Reproductive Medicine.
AD  - Department of Physiology.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Anti-Infective Agents, Local)
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Insulin)
RN  - 0 (PPAR gamma)
RN  - 0 (Slc2a4 protein, mouse)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 4NM5039Y5X (Triclosan)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - Q51BO43MG4 (Thyroxine)
SB  - IM
MH  - Adipose Tissue/drug effects/metabolism
MH  - Animals
MH  - Anti-Infective Agents, Local/*toxicity
MH  - Biomarkers/blood
MH  - Blood Glucose/drug effects/metabolism
MH  - Diabetes, Gestational/blood/*chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - Female
MH  - Gestational Age
MH  - Glucose Transporter Type 4/metabolism
MH  - Insulin/blood
MH  - *Insulin Resistance
MH  - Insulin-Secreting Cells/*drug effects/metabolism
MH  - Male
MH  - Maternal Exposure/adverse effects
MH  - Mice, Inbred ICR
MH  - Muscle, Skeletal/drug effects/metabolism
MH  - PPAR gamma/metabolism
MH  - Phosphorylation
MH  - Pregnancy
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/drug effects
MH  - Thyroid Gland/*drug effects/metabolism
MH  - Thyroxine/*blood
MH  - Time Factors
MH  - Triclosan/*toxicity
MH  - Triiodothyronine/blood
OTO - NOTNLM
OT  - Triclosan
OT  - gestational diabetes mellitus
OT  - insulin resistance
OT  - thyroid hormones
EDAT- 2017/10/04 06:00
MHDA- 2018/06/26 06:00
CRDT- 2017/10/04 06:00
PHST- 2017/10/04 06:00 [pubmed]
PHST- 2018/06/26 06:00 [medline]
PHST- 2017/10/04 06:00 [entrez]
AID - 4082719 [pii]
AID - 10.1093/toxsci/kfx166 [doi]
PST - ppublish
SO  - Toxicol Sci. 2017 Nov 1;160(1):150-160. doi: 10.1093/toxsci/kfx166.