title: Preeclampsia, insulin signalling and immunological dysfunction: a fetal, maternal or placental disorder?
abstract: An inappropriate glycogen accumulation in preeclamptic placentas was described as secondary to biochemical alterations. Insulin resistance is widely accepted to be associated with preeclampsia, although its basis remain unclear. A family of putative insulin mediators, namely inositol phosphoglycans, were described to exert many insulin-like effects on lipid and glucose metabolism. A definite association between the P-type mediator (P-IPG) and preeclampsia was reported, being increased in placenta, urine, amniotic fluid and cord blood from human preeclamptic pregnancies. A strong link exists between insulin resistance and inflammation. Clear features of insulin resistance and systemic inflammatory activation were described in preeclampsia. It may be a consequence of the immunological dysfunction that occurs in preeclampsia that is temporized during sperm exposure and co-habitation which confuses the maternal immune network to perceive 'danger'. The over-expression of P-IPG during preeclampsia may be a counter-regulatory mechanism to insulin resistance since these molecules mimic insulin action. Besides, the lipidic form of P-IPG was reported to be similar to endotoxins, and may represent the 'danger signa'. We propose here a novel working theory on insulin resistance and preeclampsia.
authors.affiliation: Department of Immunology and Molecular Pathology, Molecular Medicine Unit, Royal Free and University College London Medical School, London, UK.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Rademacher
authors.forename: Khalid
authors.initials: K
authors.lastname: Gumaa
authors.forename: Marco
authors.initials: M
authors.lastname: Scioscia
mesh_terms: D016640:Diabetes, Gestational / Q000276:immunology / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000502:physiology; D006801:Humans; D007154:Immune System Diseases / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007295:Inositol Phosphates / Q000276:immunology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D010920:Placenta / Q000378:metabolism*; D011134:Polysaccharides / Q000276:immunology / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction
chemical_list: D007295:Inositol Phosphates; D007328:Insulin; D011134:Polysaccharides; C028039:inositol phosphate glycan