Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overt diabetes and gestational diabetes (1-2.5% of all pregnancies) has been related to perinatal mortality, increased macrosomia and increased frequency of other pregnancy complications. Human placental lactogen (hPL), a hormone similar to growth hormone, is produced by the placenta and is a potent antagonist to insulin action. While hPL's presence in maternal circulation induces a sparing effect on nutrients including glucose, it exacerbates diabetes during pregnancy and may well relate to other clinical complications. To explore possible regulation of hPL in diabetic pregnancy and specifically to examine gestational diabetes, we have evaluated the levels of placental mRNA coding for hPL synthesis as well as other parameters from diabetic and normal term patients. By in vitro translation assays using nuclease-treated reticulocyte lysate, no substantial differences in translatable hPL-mRNA were observed when comparing normal term (3.5% of total synthesis), gestational diabetic (3.4%) and Type C diabetic (3.5%). However, translatable hPL-mRNA in Type R diabetes which was 2.7% of total synthesis was slightly reduced in comparison to normal term. To determine more directly hPL-mRNA levels in gestational diabetic placentas and normal term placentas, total RNA preparations were evaluated qualitatively by northern blot and quantitatively by dot blot of RNA and cDNA hybridization to a nick-translated hPL-pMB9 plasmid. The northern blot revealed no major size differences of the mRNA and the dot blot hybridization was quantitatively similar for both gestational diabetics and normal terms per unit of total RNA. By direct analysis of DNA per g tissue we found the DNA content of placentas from gestational diabetics and normal term to be statistically the same.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1985 Jan
PMID:Comparisons of human placental lactogen mRNA levels from placentas of diabetics and normal term. 397 53

Monoclonal antibodies generated against normal and leukemic human leukocytes were tested for their differential reactivity with leukemia and lymphoma cell lines as well as with circulating lymphoid and myeloid leukemic cells by means of immuno-scanning electron microscopy (immuno-SEM). Anti-T (OKT3), anti-mu-chain, anti-CALLA (J5), anti-BA-1, anti-BA-2, and anti-nonlymphoid (Mol) monoclonal antibodies were covalently conjugated to polystyrene latex microspheres (immunolatex), using a two-step glutaraldehyde reaction, and subsequently incubated with the various cell types. Cultured B-type Burkitt lymphoma cells (Daudi) and chronic lymphocytic leukemia (CLL) cells displayed extensive labeling with monoclonal anti-mu, anti-B1, and anti-BA-1 immunolatex conjugates, while cultured malignant T cells (HD-Mar) showed positive labeling with OKT3 immunolatex alone. Cultured myelomonocytic cells (GDM-1) and cells obtained from patients with acute myeloblastic (AML) and monoblastic leukemia (AMoL) labeled only with anti-Mol immunolatex, while cultured promyelocytic cells (HL-60) displayed far less labeling with this conjugate. Common-type acute lymphoblastic leukemia (C/ALL) cells were labeled predominantly with the J5 (anti-CALLA) and anti-BA-2 immunolatex conjugates. Evidence is presented indicating that immuno-SEM employing monoclonal antibodies is a reproducible technique which may be used in the study of leukocyte maturation and may provide additional information in the classification of poorly differentiated leukemias.
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PMID:Utilization of monoclonal antibodies and immuno-scanning electron microscopy for the positive identification of human leukemic cells. 658 Nov 72

Insulin receptor binding was examined in the microvillous membranes of mid-term (20-22 weeks of gestation, MT) and full-term (FT) placentas from patients with gestational diabetes mellitus (GDM) and in normal pregnant control (N). Mid-term placentas were obtained from patients who have had spontaneous abortion. The maximum per cent specific binding (%SB) in MT placenta for GDM was significantly lower (4.8%) compared with the FT placenta (22%, p < 0.001), while in the N group the maximum per cent specific binding for MT placenta was 14.1% compared with 26% for the FT placenta (p < 0.001). Binding data from FT placenta of well-controlled GDM patients were similar with the FT placenta from N group (22% SB for GDM VS 26% SB for N). Even as there were similarities in the binding characteristics of FT placentas from both groups the placental membrane protein content in the GDM group was lower by 50% compared with the N control (2.5 +/- 0.11 VS 4.8 +/- 0.15 mg protein/g placenta respectively, p < 0.001) suggesting that in the GDM group achieving a tight glycemic control could improve receptor affinities. Data from the competitive binding assay of GDM patients showed that the insulin necessary to achieve 50% inhibition (ID50) was significantly lower in MT compared with the FT placenta (0.9 x 10(-9) M VS 3.8 x 10(-9) M, p < 0.001) but in the N placenta there was no alteration in the ID50 of MT and FT placentas (3.1 x 10(-9) M VS 4 x 10(-9) M, p < 0.01, respectively). The present study demonstrated that in GDM the placental insulin receptor binding was significantly lower in spontaneously aborted placenta compared with placentas collected at full-term. Furthermore, these data suggest that the objective to achieve a tight glycemic control in GDM patients could optimize insulin receptor function similar to that of a normal pregnancy. Thus a full term placenta from GDM patients under a well managed glycemic control throughout the entire duration of pregnancy would result in an optimum insulin receptor function.
Mol Cell Biochem 1995 Oct 04
PMID:Insulin receptor binding from mid-term and full-term placentas of patients with gestational diabetes mellitus and normal pregnant women. 858 10

Leptin expression in third trimester placenta (p) and leptin concentrations in umbilical cord blood (cb) were investigated in normal pregnancies [n = 10 (p), 31 (cb)] and abnormal pregnancies complicated with (i) maternal insulin-dependent diabetes [IDDM: n = 3 (p), 13 (cb)], (ii) gestational diabetes [GD: n = 2 (p), 10 (cb)] and (iii) fetal growth retardation [FGR: n = 5 (p), 5 (cb)]. By in-situ hybridization and immunohistochemistry, placental leptin mRNA and protein were co-localized to the syncytiotrophoblast and villous vascular endothelial cells. Leptin receptor was immunolocalized to the syncytiotrophoblast. Relative to controls, the FGR group was characterized by low concentrations of placental and cord blood leptin. In a twin pregnancy, the normal-sized infant exhibited more placental and cord blood leptin than its growth-retarded twin. In contrast, both diabetic groups exhibited high concentrations of placental leptin mRNA and protein. The IDDM group exhibited the highest concentrations of leptin in cord blood. No change was observed in the expression of the leptin receptor in either the growth-retarded or diabetic pregnancies. In conclusion, the localization of placental leptin suggests that it may be released into both maternal and fetal blood. Furthermore, in fetal growth-retarded and diabetic pregnancies, the changes in leptin expression in the placenta and in leptin concentrations in umbilical cord blood appear to be related.
Mol Hum Reprod 2000 Aug
PMID:Placental leptin in normal, diabetic and fetal growth-retarded pregnancies. 1090 88

After a short description of normal glucose homeostasis, recent findings in relation to insulin release in three groups with a high risk of future development of type 2 diabetes are described. Hyperglycemic clamps in subjects with impaired glucose tolerance (IGT) clearly indicate that pancreatic beta cell function is decreased, in addition to the decreased insulin sensitivity. In women with former gestational diabetes mellitus (GDM), insulin release is also lower than in controls. In Caucasian first-degree relatives (FDRs) with normal glucose tolerance, various studies have shown that beta cell function is lower than in controls, while on the average insulin sensitivity is normal. This implies that beta cell function is disturbed earlier in subjects at risk of developing diabetes than is often appreciated. In the near future, the genetic studies currently underway will presumably unravel the pathogenesis of disturbances both in insulin secretion and in insulin action, in type 2 diabetes mellitus.
Mol Cell Endocrinol 2002 Nov 29
PMID:Early disturbances in insulin secretion in the development of type 2 diabetes mellitus. 1243 13

Compared to normal-weight women, obese women have an increased risk of infertility and pregnancy complications. The most consistently described pregnancy complications are hypertensive disorders, gestational diabetes mellitus, thromboembolic events, and cesarean section. Fetal and neonatal complications may include congenital malformations, macrosomia, and shoulder dystocia. The literature suggests that women with a body mass index (BMI) >or=30 have approximately double the risk of having a child with a neural tube defect (NTD) compared to normal-weight women, and the increased risk associated with higher maternal body weight does not appear to be modified by folic acid supplementation. The Public Affairs Committee of the Teratology Society supports the public health initiatives identified by the U.S. Food and Drug Administration in 2004 and the research initiatives identified by the National Institutes of Health in 2004. The Public Affairs Committee recommends that clinicians counsel women about appropriate caloric intake and exercise and that health-care providers educate parents about appropriate childhood nutrition. Breast-feeding should be encouraged based on evidence of a protective effect against childhood obesity, as well as other health advantages.
Birth Defects Res A Clin Mol Teratol 2006 Feb
PMID:Teratology Public Affairs Committee position paper: maternal obesity and pregnancy. 1646 72

Maternal diabetes significantly increases the risk of congenital malformations, and the mechanisms involved are not yet clarified. This study was designed to address peroxisome proliferator-activated receptor delta (PPARdelta) involvement in diabetic embryopathy. We investigated the concentrations of PPARdelta and its endogenous agonist prostaglandin (PG)I(2), as well as the effect of PPARdelta activation on lipid metabolism and PGE(2) concentrations in embryos from control and streptozotocin-induced diabetic rats during early organogenesis. Embryos from diabetic rats showed decreased concentrations of PPARdelta and its endogenous agonist PGI(2) when compared with controls. In embryos from control rats, the addition of the PPARdelta activators (cPGI(2) and PGA(1)) increased embryonic phospholipid levels and de novo phospholipid synthesis studied using (14)C-acetate as a tracer. PGE(2) formed from arachidonate released from phospholipid stores was also up-regulated by PPARdelta activators. In embryos from diabetic rats, reduced phospholipid synthesis and PGE(2) content were observed, and clearly up-regulated by cPGI(2) additions to values similar to those found in control embryos. These data suggest that PPARdelta may play an important role in lipid metabolic and signalling pathways during embryo organogenesis, developmental pathways that are altered in embryos from diabetic rats, possibly as a result of a reduction in levels of PPARdelta and its endogenous activator PGI(2).
Mol Hum Reprod 2007 Feb
PMID:PPARdelta and its activator PGI2 are reduced in diabetic embryopathy: involvement of PPARdelta activation in lipid metabolic and signalling pathways in rat embryo early organogenesis. 1714 78

The nucleotide degrading enzymes, ectonucleotidases, present on the platelet surface of human pregnant with a normal (without complications) or high risk for thrombosis (hypertension and gestational diabetes) were studied. NTPDase (E.C. 3.6.1.5, CD39) and 5'-nucleotidase (E.C. 3.1.3.5, CD73) activities of four patient groups, non-pregnant (NP, n = 18), pregnant without complications (P, n = 25), pregnant with hypertension (HP, n = 15) and pregnant with gestational diabetes mellitus (GDP, n = 10), were analyzed. Increased NTPDase activities were observed in the groups P (37.0%, S.D. = 2.03 and 34.0%, S.D. = 3.19), HP (40.0%, S.D. = 3.32 and 56.0%, S.D. = 3.25) and GDP (23.0%, S.D. = 2.30 and 42.0%, S.D. = 2.26) in comparison to the control group NP (p < 0.01, S.D. = 1.92 and S.D. = 2.48) when ATP and ADP were used as substrate, respectively. AMP was used as substrate to determine the 5'-nucleotidase activities, which showed to be elevated in the groups P (45.0%, S.D. = 1.73), HP (54.0%, S.D. = 2.64) and GDP (68.0%, S.D. = 1.69) when compared to the control group NP (p < 0.01, S.D. = 1.26). However, no statistically significant differences were observed between the groups P, HP and GDP. As a consequence, the enhanced ATP, ADP and AMP hydrolysis was ascribed to the pregnancy itself, independent of a normal or high risk for thrombosis. The enhanced NTPDase and 5'-nucleotidase activities in platelets suggest that these enzymes are involved in the thromboregulation process in the pregnancy.
Mol Cell Biochem 2007 Oct
PMID:NTPDase and 5'-nucleotidase activities in platelets of human pregnants with a normal or high risk for thrombosis. 1755 93

Conventional wisdom states that associations between fetal growth and diseases in pregnancy, such as pregnancy-induced hypertension (PIH) and gestational diabetes (GDM), result from effects of the mother's genotype or environment acting on her physiology which subsequently affect the fetus. However, recent evidence from human mothers carrying macrosomic offspring with Beckwith Wiedemann syndrome and pregnant mice carrying p57(kip2)-null offspring suggest that variation in the fetal genome can modify maternal physiology to increase fetal nutrient delivery and optimise growth. These are some of the first documented examples of such effects, whereby the genome of one individual directly affects the physiology of another related individual from the same species. We propose that this mechanism is involved in the aetiology of PIH and GDM.
Trends Mol Med 2007 Oct
PMID:Does the fetal genotype affect maternal physiology during pregnancy? 1790 Sep 86

Breast cancer resistance protein (BCRP) is most abundantly expressed in the apical membrane of placental syncytiotrophoblasts, suggesting that it may protect the fetus by impeding drug penetration across the placental barrier. Glyburide (GLB) is an antidiabetic drug routinely used to treat gestational diabetes. In this study, we first determined whether GLB is a BCRP/Bcrp1 substrate. The intracellular [(3)H]GLB concentrations in Madin-Darby canine kidney (MDCK)/BCRP cells were significantly lower than those in MDCK/vector cells. The addition of 10 muM fumitremorgin C, a specific BCRP inhibitor, significantly increased the intracellular [(3)H]GLB concentrations approximately 2-fold in MDCK/BCRP cells, but it had no effect in MDCK/vector cells. Similar results were obtained using MDCKII parent and MDCKII/Bcrp1 cells. GLB was also shown to be a BCRP/Bcrp1 substrate in transwell transport experiments. We then examined whether Bcrp1 limits fetal distribution of GLB in the pregnant mouse. GLB was administered by retro-orbital injection to the wild-type and Bcrp1(-/-) pregnant mice. The maternal plasma samples and fetuses were collected at various times (0.5-240 min) after drug administration. The GLB concentrations in the maternal plasma samples and homogenates of fetal tissues were determined by high-performance liquid chromatography/mass spectrometry. Although the maternal plasma area under the concentration-time curves (AUCs) of GLB in the wild-type and Bcrp1(-/-) pregnant mice were comparable, the fetal AUC of GLB in the Bcrp1(-/-) pregnant mice was approximately 2 times greater than that in the wild-type pregnant mice. These results suggest that GLB is a BCRP/Bcrp1 substrate, and Bcrp1 significantly limits fetal distribution of GLB in the pregnant mouse, but it has only a minor effect on the systemic clearance of the drug.
Mol Pharmacol 2008 Mar
PMID:The breast cancer resistance protein (Bcrp1/Abcg2) limits fetal distribution of glyburide in the pregnant mouse: an Obstetric-Fetal Pharmacology Research Unit Network and University of Washington Specialized Center of Research Study. 1807 76


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