Insulin resistance in human preeclamptic placenta is mediated by serine phosphorylation of insulin receptor substrate-1 and -2.
J Clin Endocrinol Metab
; 91(2): 709-17, 2006 Feb.
Article
em En
| MEDLINE
| ID: mdl-16332940
ABSTRACT
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 ANDSETTING:
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 12 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.
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Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Placenta
/
Pré-Eclâmpsia
/
Resistência à Insulina
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Itália