Assessment of the expression of IRβ, IRS-1, IRS-2 and IGF-IRβ in a rat model of intrauterine growth restriction

Abstract

To investigate glomerular development and expression of insulin and insulin-like growth factor receptors in an experimental model of intrauterine growth restriction (IUGR). 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. 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. IUGR fetuses had less glomeruli and alterations in insulin receptors, which may be associated with an increased risk of disease occurrence in adulthood