Assessment of the Expression of IRβ, IRS-1, IRS-2 and IGF-IRβ in a Rat Model of Intrauterine Growth Restriction

Abstract

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

Effect of insulin‐like growth factor‐I during the early postnatal period in intrauterine growth‐restricted rats

“…This may indicate the recovery phase after the ischemic insult by UAL. In previous reports, Igf‐ir mRNA level at birth in the liver of IUGR rats was significantly higher in unilateral URL and was not significantly different in bilateral URL compared with control rats, but we could not find any reason for the lower hepatic Igf‐ir mRNA expression in IUGR rats on PND 25.…”

The role of gut-liver axis in the restriction of intrauterine growth in a model of experimental gastroschisis

“…A way to control the insulin resistance would be to increase the expression of IRS-2, which partially compensates the lower amount of IRS-1, allowing a regulation of glucose levels in fetal organism, so that hyperglycemia does not happen 12 Analyzing the IGF-IRβ levels, we found that it is increased in the liver and intestine of fetuses with gastroschisis, similar results were found on the IUGR model in rats 14 . In a fetal sheep model, it was also found an increased IGF-IRβ, although on skeletal muscles, suggesting that the increase is a response to low circulating hormone concentrations in fetuses with IUGR 13 .…”

RON Receptor Tyrosine Kinase Regulates Epithelial Mesenchymal Transition and the Expression of Pro-Fibrotic Markers via Src/Smad Signaling in HK-2 and NRK49F Cells

“…FGFR1- and FGFR2- null mice cause early embryonic lethality [30,31], and gene inactivation of PDGFRβ in mice results in a lack of mesangial cells and pericytes of the glomerular capillaries [32]. In addition, decreased protein expression of IGF2R in the rat intrauterine growth restriction has been associated with decreased glomerular number, and IGFR has been associated with promoting nephrogenesis and kidney organogenesis [33]. These findings were associated with the release of various cytokines such as interleukin-1β (IL-1β), IL-6, IL-8, TNF-α, and monocyte chemoattractant protein-1, and multiple signaling [34,35].…”