PMID- 30597186
OWN - NLM
STAT- MEDLINE
DCOM- 20190725
LR  - 20190725
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 413
DP  - 2019 Feb 1
TI  - Developmental exposure to DEHP alters hepatic glucose uptake and transcriptional 
      regulation of GLUT2 in rat male offspring.
PG  - 56-64
LID - S0300-483X(18)30462-1 [pii]
LID - 10.1016/j.tox.2018.12.004 [doi]
AB  - Type-2-diabetes (T2D) is a long term metabolic disorder characterized by high 
      blood glucose and insulin resistance. It has become an alarming issue globally 
      due to tremendous increase in number of new subjects every year. Apart from the 
      classical factors, there are few non-classical factors such as environmental 
      pollutants, endocrine disrupting chemicals (EDCs) which also play a major role in 
      pathogenesis of T2D. Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used 
      plasticizer which is an endocrine disrupting chemical. It is used in the plastic 
      industry to give flexibility and durability. Its widespread use resulted in 
      constant presence in the environment and human are under high risk of exposure to 
      this compound. There are literature available stating that DEHP has an impact on 
      glucose homeostasis. Glucose transporter 2 (GLUT2) is a principal transporter of 
      glucose in liver and it is a bi-directional transporter. We investigated whether 
      DEHP exposure during gestation and lactation alters transcriptional regulation of 
      GLUT2 and epigenetics changes in the rat F(1) male offspring at adulthood. 
      Pregnant rats were divided into three groups and administered with DEHP (10 and 
      100 mg /kg /day) or olive oil from gestational day (GD) 9- to postnatal day (PND) 
      21 through oral gavage. DEHP treated rats showed decreased glucose uptake and 
      oxidation, decreased mRNA levels of insulin receptor (IR), GLUT2 and reduced 
      GLUT2 protein in cytosol but unaltered level in plasma membrane. There are three 
      main transcription factors (SREBP1c, HNF3beta and HNF1alpha) involved in the regulation 
      of GLUT2 gene and all these proteins were reduced in DEHP exposed groups. A weak 
      interaction of the transcription factors (SREBP1c & HNF1alpha) with GLUT2 gene 
      promoter was observed in DEHP-treated groups. Hyper- methylation of IR and GLUT2 
      gene promoter was observed in both the DEHP-exposed groups compared to control. 
      The present study reveals that DEHP exposure alters transcriptional regulation of 
      GLUT2 and imposes epigenetic alteration in IR and GLUT2 gene promoters which 
      plays a significant role in the development of metabolic abnormality in F(1) male 
      offspring at adulthood.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Rajagopal, Gokulapriya
AU  - Rajagopal G
AD  - Department of Endocrinology, Dr ALM Post Graduate Institute of Basic Medical 
      Sciences, University of Madras, Taramani, Chennai 600 113, India.
FAU - Bhaskaran, Ravi Sankar
AU  - Bhaskaran RS
AD  - Department of Endocrinology, Dr ALM Post Graduate Institute of Basic Medical 
      Sciences, University of Madras, Taramani, Chennai 600 113, India.
FAU - Karundevi, Balasubramanian
AU  - Karundevi B
AD  - Department of Endocrinology, Dr ALM Post Graduate Institute of Basic Medical 
      Sciences, University of Madras, Taramani, Chennai 600 113, India. Electronic 
      address: kbala82@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181228
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Glucose Transporter Type 2)
RN  - 0 (Plasticizers)
RN  - 0 (Slc2a2 protein, rat)
RN  - C42K0PH13C (Diethylhexyl Phthalate)
RN  - IY9XDZ35W2 (Glucose)
MH  - Animals
MH  - Diethylhexyl Phthalate/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 2/antagonists & inhibitors/*biosynthesis/genetics
MH  - Liver/drug effects/*metabolism
MH  - Male
MH  - Plasticizers/*toxicity
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/chemically induced/genetics/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Transcription, Genetic/drug effects/physiology
OTO - NOTNLM
OT  - DEHP
OT  - Epigenetics
OT  - GLUT2
OT  - Glucose homeostasis
OT  - Insulin resistance
EDAT- 2019/01/01 06:00
MHDA- 2019/07/26 06:00
CRDT- 2019/01/01 06:00
PHST- 2018/10/15 00:00 [received]
PHST- 2018/12/14 00:00 [revised]
PHST- 2018/12/27 00:00 [accepted]
PHST- 2019/01/01 06:00 [pubmed]
PHST- 2019/07/26 06:00 [medline]
PHST- 2019/01/01 06:00 [entrez]
AID - S0300-483X(18)30462-1 [pii]
AID - 10.1016/j.tox.2018.12.004 [doi]
PST - ppublish
SO  - Toxicology. 2019 Feb 1;413:56-64. doi: 10.1016/j.tox.2018.12.004. Epub 2018 Dec 
      28.