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Marco Scioscia, Khalid Gumaa, Sirilaksana Kunjara, Malcolm A. Paine, Luigi E. Selvaggi, Charles H. Rodeck, Thomas W. Rademacher, Insulin Resistance in Human Preeclamptic Placenta Is Mediated by Serine Phosphorylation of Insulin Receptor Substrate-1 and -2, The Journal of Clinical Endocrinology & Metabolism, Volume 91, Issue 2, 1 February 2006, Pages 709–717, https://doi.org/10.1210/jc.2005-1965
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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.
