Insulin Resistance in Human Preeclamptic Placenta is Mediated by Serine Phosphorylation of Insulin Receptor Substrate-1 and -2
Overview
Authors
Affiliations
Context: Preeclampsia is a severe complication of human pregnancy often associated with maternal risk factors. Insulin resistance represents a major risk for developing preeclampsia during pregnancy.
Objective: A putative second messenger of insulin, inositol phosphoglycan P type (P-IPG), was previously shown to be highly increased during active preeclampsia. Its association with insulin resistance was investigated.
Design And Setting: A cross-sectional study was carried out in a referral center.
Patients: Nine preeclamptic (PE) and 18 healthy women were recruited and matched for maternal age, body mass index, parity, and ethnicity in a 1:2 ratio. Placental specimens were collected immediately after delivery.
Intervention: Placental tissue was incubated with insulin and P-IPG production assessed. Insulin signaling proteins were subsequently studied by immunoblotting.
Results: P-IPG extracted from human term placentas upon incubation with insulin was found to be far lower in those with preeclampsia than controls (P < 0.001). Immunoblotting studies revealed serine phosphorylation of insulin receptor substrate-1 and -2 in PE placentas (P < 0.001) with downstream impairment of insulin signaling. The activation of the p85 regulatory subunit of phosphatidylinositol 3- kinase was markedly decreased in PE samples (P < 0.001).
Conclusions: These findings highlight the importance of P-IPG in active preeclampsia and demonstrate a substantially different response to the insulin stimulus of human PE placentas. Acquired alterations in activation of proteins involved in insulin signaling may play a role in the complex pathogenesis of preeclampsia, probably as a consequence of the immunological dysfunction that occurs in this syndrome. These results seem to confirm an insulin-resistant state in PE placenta and shed a different light on its role in the pathogenesis of this disease with potential therapeutic implications.
Zhu H, Xiao H, Li L, Yang M, Lin Y, Zhou J Cell Genom. 2024; 4(10):100631.
PMID: 39389014 PMC: 11602577. DOI: 10.1016/j.xgen.2024.100631.
Aquaporins in Fetal Development.
Martinez N, Damiano A Adv Exp Med Biol. 2023; 1398:251-266.
PMID: 36717499 DOI: 10.1007/978-981-19-7415-1_17.
Jiang S, Chen Q, Liu H, Gao Y, Yang X, Ren Z Mol Ther Nucleic Acids. 2020; 22:684-695.
PMID: 33230466 PMC: 7585871. DOI: 10.1016/j.omtn.2020.09.033.
Chen Q, Jiang S, Liu H, Gao Y, Yang X, Ren Z Cell Death Dis. 2020; 11(7):583.
PMID: 32719429 PMC: 7385659. DOI: 10.1038/s41419-020-02796-0.
Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus.
Rachdaoui N Int J Mol Sci. 2020; 21(5).
PMID: 32150819 PMC: 7084909. DOI: 10.3390/ijms21051770.