PMID- 18828053
OWN - NLM
STAT- MEDLINE
DCOM- 20090122
LR  - 20131121
IS  - 1476-4954 (Electronic)
IS  - 1476-4954 (Linking)
VI  - 21
IP  - 9
DP  - 2008 Sep
TI  - Effect of fetal dexamethasone exposure on the development of adult insulin 
      sensitivity in a rat model.
PG  - 623-8
LID - 10.1080/14767050802213073 [doi]
AB  - OBJECTIVE: A rat model was designed to determine if fetal dexamethasone exposure 
      is associated with decreased insulin sensitivity in adulthood, manifested as 
      decreased binding of p85 to phosphorylated insulin receptor substrate-1 (IRS-1) 
      within the phosphatidylinositol 3-kinase (PI 3-kinase) pathway of insulin 
      signaling. Additionally, the study investigated whether a differential effect 
      exists in male and female rodent offspring, such that females demonstrate 
      decreased binding of p85 to IRS-1 after exposure to dexamethasone in utero. 
      METHODS: Timed-pregnant Sprague-Dawley rats received either tap water or 
      dexamethasone in drinking water from day 13 of gestation until delivery. Fasting 
      male and female offspring from each group were sacrificed on day 50 of life, and 
      half of these rats were given insulin subcutaneously prior to sacrifice. 
      Adipocyte, skeletal muscle, and liver cell lysates were analyzed by 
      immunoprecipitation and Western blotting of IRS-1 and IRS-1-associated p85. 
      RESULTS: In all tissues examined, a significant inverse relationship was found 
      between dexamethasone treatment in utero and association of p85 with IRS-1 in 
      adulthood. p85 association with IRS-1 was similar in tissues from fasting and 
      insulin-stimulated states. Furthermore, tissues of male and female rats 
      demonstrated similar binding of p85 to IRS-1. CONCLUSIONS: In a rat model, fetal 
      exposure to dexamethasone was associated with decreased insulin signaling at the 
      level of p85 binding to IRS-1, a proximal step in insulin signaling within the PI 
      3-kinase pathway. This effect did not appear to be enhanced by administration of 
      insulin prior to sacrifice, nor was a sex-dependent differential effect noted.
FAU - O'Brien, Karen
AU  - O'Brien K
AD  - Women and Infants' Hospital of Rhode Island, Providence, RI, USA. 
      Karen_o'brien_MD@sshosp.org
FAU - Sekimoto, Hiroko
AU  - Sekimoto H
FAU - Boney, Charlotte
AU  - Boney C
FAU - Malee, Maureen
AU  - Malee M
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Matern Fetal Neonatal Med
JT  - The journal of maternal-fetal & neonatal medicine : the official journal of the 
      European Association of Perinatal Medicine, the Federation of Asia and Oceania 
      Perinatal Societies, the International Society of Perinatal Obstetricians
JID - 101136916
RN  - 0 (Glucocorticoids)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, rat)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Animals
MH  - Dexamethasone/administration & dosage/*adverse effects
MH  - Female
MH  - Glucocorticoids/administration & dosage/*adverse effects
MH  - Glucose Metabolism Disorders/etiology
MH  - Insulin/metabolism
MH  - Insulin Receptor Substrate Proteins/*metabolism
MH  - Male
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/chemically induced/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2008/10/02 09:00
MHDA- 2009/01/23 09:00
CRDT- 2008/10/02 09:00
PHST- 2008/10/02 09:00 [pubmed]
PHST- 2009/01/23 09:00 [medline]
PHST- 2008/10/02 09:00 [entrez]
AID - 903250622 [pii]
AID - 10.1080/14767050802213073 [doi]
PST - ppublish
SO  - J Matern Fetal Neonatal Med. 2008 Sep;21(9):623-8. doi: 
      10.1080/14767050802213073.