Assessment of the expression of IRβ, IRS-1, IRS-2 and IGF-IRβ in a rat model of intrauterine growth restriction.
OBJECTIVE
To investigate glomerular development and expression of insulin and insulin-like growth factor receptors in an experimental model of intrauterine growth restriction (IUGR).


METHODS
We studied three groups of Sprague-Dawley fetuses: IUGR - restricted by ligation of the right uterine artery; C-IUGR - left horn controls, and EC - external controls (non-manipulated). Body and organs were weighed, and glomerular number and volume were analyzed. Expression of IRβ, IRS-1, IRS-2 and IGF-IRβ was analyzed in liver, intestine and kidneys by immunoblotting.


RESULTS
Organ/body weight ratios were similar. In IUGR, glomerular number and volume were increased compared to C-IUGR and EC (p<0.001). In the IUGR liver, increases were found in IGF-IRβ compared to C-IUGR and EC; IRβ compared to EC, and IRS-2 compared to C-IUGR. However, decreases in IRβ were noted in IUGR compared to C-IUGR; IRS-1 compared to C-IUGR and EC, and IRS-2 compared to EC. In IUGR intestine, increases were detected in IRβ, IRS-1 and IGF-IRβ compared to C-IUGR and EC. In IUGR kidneys, increases were observed in IRβ and IGF-IRβ compared to C-IUGR and EC, and IRS-1 compared to EC. Decreased IRS-2 in the intestine and kidney were noticed in IUGR compared to C-IUGR and EC.


CONCLUSIONS
IUGR fetuses had less glomeruli and alterations in insulin receptors, which may be associated with an increased risk of disease occurrence in adulthood.
Bueno
Marcia Pereira
MP
Department of Obstetrics and Gynecology, University of Campinas, Brazil.
Guadagnini
Dioze
D
Gonçalves
Frances Lilian Lanhellas
FL
Barini
Ricardo
R
Saad
Mario José Abdalla
MJ
Schmidt
Augusto Frederico
AF
Sbragia
Lourenço
L
D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000503:physiopathology; D005333:Fetus / Q000737:chemistry / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000032:analysis / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000737:chemistry / Q000254:growth & development; D007668:Kidney / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism; D009929:Organ Size; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000032:analysis / Q000378:metabolism*; D017451:Receptors, Somatomedin / Q000032:analysis / Q000378:metabolism*
D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D017451:Receptors, Somatomedin; D011972:Receptor, Insulin