Association of insulin-like growth factor 2 with the insulin-linked polymorphic region in cultured fetal thymus cells.
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ABSTRACT:
SUBMITTER: Wang Y
PROVIDER: S-EPMC3906629 | biostudies-literature | 2009 Sep
REPOSITORIES: biostudies-literature
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Project description:Insulin capture by a G-quadruplex DNA oligonucleotide containing a two-repeat sequence of the insulin-linked polymorphic region (ILPR) of the human insulin gene promoter region is reported. The immobilized oligonucleotide was demonstrated to capture human insulin from standard solutions and from nuclear extracts of pancreatic cells with high selectivity, using affinity MALDI mass spectrometry and affinity capillary chromatography. Insulin was preferentially captured by the two-repeat ILPR oligonucleotide over another G-quadruplex-forming oligonucleotide, the thrombin-binding aptamer, as well as over a single repeat of the ILPR sequence that is not capable of forming the G-quadruplex architecture. Binding was shown to involve the beta chain of insulin. The discovery raises the possibility that insulin may bind to G-quadruplex DNA formed in the ILPR in vivo and thereby play a role in modulation of insulin gene expression, and it provides a basis for design of insulin analogues to probe this hypothesis. The availability of a DNA ligand to human insulin has analytical importance as well, offering an alternative to antibodies for in vitro or in vivo detection and sensing of insulin as well as its isolation and purification from biological samples.
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Project description:PurposeFetal macrosomia is associated with perinatal injuries. The purpose of this study was to assess the relationship between fetal insulin, insulin-like Growth factor-1(IGF-1), and macrosomia in a resource-limited setting.MethodThis was a case-control study at tertiary and secondary health facilities in Lagos, Nigeria. One hundred and fifty mother-neonate pairs were recruited, and their socio-demographic and obstetric history was recorded. Fetal cord venous blood was collected at birth, and neonatal anthropometry was measured within 24hrs of life. Insulin and IGF-1 assay were measured with Enzyme-Linked Immunosorbent Assay (ELISA). Pearson's Chi-square was used to assess the association between categorical variables and macrosomia. Spearman's rank correlation of insulin, IGF-1, and fetal anthropometry was performed. Multivariable logistic regression was used to evaluate the association of insulin and IGF-1 with fetal birth weight. A statistically significant level was set at P-value < 0.05.ResultsMacrosomic neonates had mean fetal weight, fetal length, and occipitofrontal circumference (OFC) of 4.15±0.26kg, 50.85±2.09cm and 36.35± 1.22cm respectively. The median Insulin (P = 0.023) and IGF-1 (P < 0.0001) were significantly higher among macrosomic neonates as compared to normal weight babies. Maternal BMI at birth (p = 0.003), neonate's gender (p < 0.001), fetal cord serum IGF-1 (p < 0.001) and insulin assay (P-value = 0.027) were significant predictors of fetal macrosomia. There was positive correlation between cord blood IGF-1 and birth weight (r = 0.47, P-value < 0.001), fetal length (r = 0.30, P-value = 0.0002) and OFC (r = 0.37, P-value < 0.001).ConclusionAmong participating mother-neonate dyad, maternal BMI at birth, neonate's gender, and fetal cord serum IGF-1 and serum insulin are significantly associated with fetal macrosomia.
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Project description:Genetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified in the human serotonin transporter (5-HTT) gene, including a repetitive sequence located in the promoter region of the locus called the serotonin transporter-linked polymorphic region (5-HTT-LPR). This polymorphism has been associated with a number of mental traits in both humans and primates, including depression, neuroticism, and harm avoidance. Some, but not all, studies found a link between the polymorphism and 5-HTT levels, leaving open the question of whether the polymorphism affects risk for mental traits via changes in 5-HTT expression. To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioral traits, we set out to develop a mouse model of the human 5-HTT-LPR. Here we describe the creation and characterization of a set of mouse lines with single-copy human transgenes carrying the short and long 5-HTT-LPR variants. Although we were not able to detect differences in expression between the short and long variants, we encountered several technical issues concerning the design of our humanized mice that are likely to have influenced our findings. Our study serves as a cautionary note for future studies aimed at studying human transgene regulation in the context of the living mouse.
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