Inositol phosphoglycans and signal transduction systems in pregnancy in preeclampsia and diabetes: evidence for a significant regulatory role in preeclampsia at placental and systemic levels.
Measurements have been made of the urinary content of inositol phosphoglycans IPG P-type and IPG A-type, putative insulin second messengers, in preeclampsia, in type I insulin-treated diabetic pregnant women and their matched control subjects, and nonpregnant women of child-bearing age. The content of IPG P-type and IPG A-type was also measured in the placenta from preeclamptic patients and from normal pregnancies. Pregnancy was associated with an increase, approximately twofold, in urinary output of IPG-P-type relative to nonpregnant controls (P<0.01). The 24-h output of IPG P-type in urine in preeclamptic women was significantly higher (2- to 3-fold) than in pregnant control subjects matched for age, parity, and stage of gestation (P<0.02). In contrast, insulin-dependent diabetic pregnant women did not show any significant change in urinary output of IPG P-type or IPG A-type relative to pregnant control subjects. Evidence for a possible relationship and correlation between the urinary excretion of IPG P-type and markers of preeclampsia, including proteinuria (r = 0.720, P<0.01), plasma aspartate transaminase (r = 0.658, P<0.05), and platelet counts (r = 0.613, P<0.05) is presented. A high yield of IPG P-type was extracted from human placenta, in preeclampsia some 3-fold higher (P = 0.03) than the normal value, whereas no IPG A-type (with lipogenic-stimulating activity) was found. Low concentrations of placental IPG A-type were detected relative to IPG P-type using assay systems dependent upon the effect of this mediator on cAMP-dependent protein kinase or on a proliferation assay using thymidine incorporation into DNA of EGFR T17 fibroblasts. It is postulated that the high urinary excretion IPG P-type in preeclampsia reflects high placental levels and relates to the accumulation of glycogen in the placenta. The paracrine effects of placental IPG P-type (stimulation off other endocrine glands and/or endothelial cells) could contribute to the pathogenesis of the maternal syndrome. A possible theoretical link between elevated placental IPG P-type and apoptosis is proposed.
Kunjara
S
S
Department of Molecular Pathology, Molecular Medicine Unit, The Windeyer Building, 46, University College London Medical School, Cleveland Street, London, W1P 6DB, England.
Greenbaum
A L
AL
Wang
D Y
DY
Caro
H N
HN
McLean
P
P
Redman
C W
CW
Rademacher
T W
TW
D000328:Adult; D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000652:urine; D004789:Enzyme Activation; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005865:Gestational Age; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D006801:Humans; D007295:Inositol Phosphates / Q000652:urine*; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011134:Polysaccharides / Q000652:urine*; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000652:urine; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D015415:Biomarkers; D007295:Inositol Phosphates; D011134:Polysaccharides; C028039:inositol phosphate glycan; D006003:Glycogen; D006006:Glycogen Synthase; D017868:Cyclic AMP-Dependent Protein Kinases