• BMB Reports
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• v.33 no.5
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• pp.396-401
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• 2000

A differential display method is used to identify novel genes whose expression is affected by treatment with ferric ammonium citrate (FAC) or desferrioxamine (DFO), an iron chelating agent in the human hepatoblastoma cell line (HepG2). These chemicals are known to deplete or increase the intracellular concentration of iron, respectively. Initially, we isolated seventeen genes whose expressions are down- or up regulated by the treatment of the chemicals, as well as their four differentially expressed genes that are designated as clone-1, -2, -3, and -4. These are further characterized by cDNA sequencing and Northern blot analysis. Through the cDNA sequencing, as well as comparing them to genes published using the NCBI BLAST program, we identified the sequence of the clone-1 that is up-regulated by the treatment of DFO. It is identical to the human insulin-like growth factor binding protein-1 (IGFBP-1). This suggests that the IGFBP-1 gene in the HepG2 cell is up-regulated by an iron depletion condition. Also, the expression of the clone-3 and -4 is up-regulated by FAC treatment and their eDNA sequences are identical to the human ferritin-fight chain and human NADH-dehydrogenase, respectively. However, the sequence of the clone-2 has no significant homology to any other known gene. Therefore, we suggest that changes of the cellular iron level in the HepG2 cell affects the transcription of cellular genes. This includes human IGFBP-1, ferritin-fight chain, and NADH-dehydrogenase. Regulation of these gene expressions may have an important role in cellular functions that are related to cellular iron metabolism.

• Korean Journal of Human Ecology
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• v.9 no.1
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• pp.81-88
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• 2006

IGFs and IGFBPs have an important role in controlling glucose homeostasis. This study was conducted to investigate the changes of insulin-like growth factor(IGF)-I. IGF-II and IGF binding proteins (IGFBPs) on fasting and postprandial state in Korean diabetes, Twenty eight healthy subjects and fifty seven diabetic patients participated in this study. The healthy subjects were not knowingly suffered from any disease and were not receiving any medical treatment, and diabetic subjects were undergo medical treatment, continuously. Weight and height were measured and body mass index (BMI) was calculated as weight (kg) divided by the square of height (m2). Blood pressure was measured. Plasma lipid profiles were analyzed by enzymatic methods, plasma Insulin and glucose levels were measured in fasting and postprandial state, respectively. The levels of serum IGFs and IGFBP-3 were measured by radioimmunoassay (RIA). The levels of glucose and insulin were significantly higher in diabetes than normal subjects on fasting as well as postprandial state (p<0.0l). The levels of IGF-I was significantly lower in diabetes than normal subjects, however in postprandial state, there was no significant difference between diabetes and control subjects, The levels of IGF-II were significantly lower in diabetes than control subjects both fasting and postpradial state, The level of IGFBP-3 were not significantly different between diabetes and normal subjects. Fasting IGF-I, IGF-II and IGFBP-3 levels were positively correlated with those levels on postprandial state, fasting IGe levels of IGF-I levels were positively correlated with fasting insulin levels, and postprandial IGF-I levels were positively correlated with fasting glucose, postprandial insulin and postprandial insulin levels, plasma triglyceride levels were correlated with plasma triglyceride levels. The IGFBP-3 levels were not correlated with IGF components, glucose, insulin and plasma lipids, These results demonstrate that in diabetes, the components IGF-I/IGFBPs system were significantly correlated with plsma glucose and insulin levels both fasting and postprandial state.

• Journal of Embryo Transfer
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• v.12 no.3
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• pp.229-246
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• 1997

Implantation is a most important biological process during pregnancy whereby conceptus establishes its survival as well as maintenance of pregnancy. During the periimplantation period, both uterine endometriurn and conceptus synthesize and secrete a host of growth factors and cytokines which mediate the actions of estrogen and /or progesterone and also exert their steroid-independent actions. Growth factors expressed by the materno-conceptal unit en masse have important roles in cell migration, stimulation or inhibition of cell proliferation, cellular differentiation, maintenance of pregnancy and materno-conceptal communications in an autorcrine /paracrine manner. The present review focuses on the role of the intrauterine IGF system during periimplantation conceptus development. The IGF system comprises of IGF- I and IGF- II ligands, types I and II IGF receptors and six or more IGF-binding proteins(IGFBPs). IGFs and IGFBPs are expressed and secreted by uterine endometrium with tissue, pregnancy stage and species specificities under the influence of estrogen, progesterone and other growth factor(s). Conceptus also synthesizes components of the IGF system beginning from a period between 2-cell and blastocyst stages. Maternal IGFs are utilized by both maternal and conceptal tissues; conceptus-derived growth factors are believed to be taken up primarily by conceptus. IGFs enhance the development of both maternal and conceptal compartments in a wide range of biological processes. They stimulate proliferation and differentiation of endometrial cells and placental precursor cells including decidual transformation from stromal cells, placental formation and the synthesis of some steroid and protein hormones by differentiated endometrial cells or placenta. It is also well-documented in a number of experimental settings that both IGFs stimulate preimplantation embryo development. In slight contrast to these, prenatal mice carrying a null mutation of IGF and /or IGF receptor gene do not exhibit any apparent growth retardation until after implantation. Reason (s) for this discrepancy between the knock-out result and the in vitro ones, however, is not known. IGFBPs, in general, are believed to inhibit IGF action within the materno-conceptal unit, thereby allowing endometrial stromal cell differentiation as well as dampening ex cessive placental invasion into maternal tissue. There is evidence, however, indicating that IGFBP can enhance IGF action depending on environrnental conditions perhaps by directioning IGF ligand to the target cell. There is also a third possibility that certain IGFBPs and their proteolytic fragments may have their own biological activities independent of the IGF. In addition to IGFBPs, IGFBP proteases including those found within the uterine tissue or lumen are thought to enhance IGF bioavailability by degrading their substrates without affecting their bound ligand. In this regard, preliminary results in early pregnant pigs suggest that a partially characterized IGFBP protease activity in uterine luminal fluid enhances intrauterine IGF bioavailability during conceptus morphological development. In summary, a number of in vitro results indicate that IGFs stimulates the development of the rnaterno-conceptal unit during the periimplantation period. IGFBPs appear to inhibit IGF action by sequestering their ligands, whereas IGFBP proteases are thought to enhance intrauterine bioavailability of IGFs. Much is remaining to be clarified, however, regarding the roles of the individual IGF system components. These include in vivo evidence for the role of IGFs in early conceptus development, identification of IGF-regulated genes and their functions, specific roles for individual IGFBPs, identification and characterization of IGFBP proteases. The intrauterine IGF club house thus will be paying a lot of attention to forthcoming results in above and other areas, with its door wide-open!

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5011-5016
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• 2013

Background: Several epidemiological studies have shown associations between colorectal cancer (CRC) risk and type 2 diabetes and obesity. Any effects would be expected to be mediated through the insulin pathway. Therefore it is possible that variants of genes encoding components of the insulin pathway play roles in CRC susceptibility. In this study, we hypothesized that polymorphisms in the genes involving the insulin pathway are associated with risk of CRC. Materials and Methods: The associations of four single nucleotide polymorphisms (SNPs) in IGF-I (rs6214), IGFBP-3 (rs3110697), INSR (rs1052371), and IRS2 (rs2289046) genes with the risk of CRC were evaluated using a case-control design with 167 CRC cases and 277 controls by the PCR-RFLP method. Results: Overall, we observed no significant difference in genotype and allele frequencies between the cases and controls for the IGF-I, IGFBP-3, INSR, IRS2 gene variants and CRC before or after adjusting for confounders (age, BMI, sex, and smoking status). However, we observed that the IRS2 (rs2289046) GG genotype compared with AA+AG genotypes has a protective effect for CRC in normal weight subjects (p=0.035, OR=0.259, 95%CI= 0.074-0.907). Conclusions: These findings do not support plausible associations between polymorphic variations in IGF-I, IGFBP-3, INSR, IRS2 genes and risk of CRC. However, the evidence for a link between the IRS2 (rs2289046) variant and risk of CRC dependent on the BMI of the subjects, requires confirmation in subsequent studies with greater sample size.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.1
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• pp.11-18
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• 2008

Human bone marrow mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tenden, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells could be isolated from marrow aspirates of human and animals. This study was designed to identify and characterize genes specifically expressed by osteogenic supplements -treated cells by suppression subtractive hybridization(SSH) method. The results were as follows: 1. 2 genes were upregulated genes in osteogenic diffeentiation of hMSCs, which is further proved by Northern blot analysis. 2. IGFBP-2 has been identified playing an important role in bone formation. 3. HF1 was also upregulated during osteogenic differentiation, but its role in bone formation is not clear yet.

• Fisheries and Aquatic Sciences
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• v.23 no.2
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• pp.3.1-3.8
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• 2020

Background: The IGF system plays important roles in controlling growth, development, reproduction, and aging of organisms. Methods: To estimate maturation of the Pacific oyster Crassostrea gigas, we investigated the expression of insulin-like growth factor (IGF) system components and sex-specific genes. To determine the role of the IGF system in the growth and spawning period of female and male oysters, we examined mRNA expression levels of the C. gigas insulin receptor-related receptor (CIR), IGF binding protein complex acid labile subunit (IGFBP_ALS), and molluscan insulin-related peptide (MIP), as well as those of vitellogenin (Vg) and receptor-type guanylate cyclase (Gyc76C) in gonads of C. gigas collected between April and October, when sex can be determined visually in this species. Results: We found that MIP, IGFBP_ALS, and CIR mRNA expression levels were dependent on sex and month and were greater in males than in females. CIR and Vg mRNA expression levels were very similar among females, whereas IGF system components and Gyc76C were very similarly expressed among males. The highest expression values were observed in May, when oysters are mature; CIR and Vg mRNA expression levels were highest in females, and those of MIP, IGFBP_ALS, CIR, and Gyc76C were highest in males. Interestingly, we observed a 1:1 proportion of females to males during this period. Conclusion: Our results suggest that IGF system components, as well as Vg and Gyc76C, are associated with sexual maturation in C. gigas.

• Clinical and Experimental Pediatrics
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• v.50 no.2
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• pp.198-204
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• 2007

Purpose : The hope that arresting pubertal developement might increase final adult height has led to an attempt to use GnRH agonist (GnRHa) in children with early puberty and poor growth prognosis. We investigated the growth-promoting effect of GnRH agonists with or without growth hormone (GH) in girls with early puberty and decreased predicted adult height (PAH). Methods : Thirty five girls with advanced bone age and early pubertal signs were randomized for treatment for about 1 year with monthly GnRHa in group 1 (n=18), or with a combination of GH and GnRHa in group 2 (n=17). The following growth parameters were compared between groups, and the difference ($\Delta$) before and after treatment : chronological age (CA), bone age (BA), $\Delta$(BA-CA), height (HT), target height (TH), predicted adult height (PAH), $\Delta$ (TH-PAH), serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein (IGFBP-3). Results : Before treatment, BA, TH, PAH Standard deviation scores (SDS), $\Delta$(TH-PAH) were not different between the two groups, but CA was higher in group 2 and $\Delta$(BA-CA) were higher in group 1 (P<0.05). After $1.06{\pm}0.93$ year of treatment, $\Delta$ (BA-CA) decreased and there were significant changes in PAH and $\Delta$ (TH-PAH), especially in group 2 (P<0.05 in group 1, and P<0.001 in group 2). In both groups, IGF-1 and IGFBP-3 were not different before and after treatment, but after treatment, IGF-1 level in group 2 was marginally higher than IGF-1 in group 1 (P<0.1). Conclusion : Compromised predicted adult height in girls with early puberty and advanced bone age was significantly improved with GnRH with/without GH treatment in the short-term period. The addition of GH to GnRHa results in a significant increase in PAH compared to GnRHa alone because GnRHa suppressed growth hormone-IGF-1 axis. For comparison of final adult height, further longitudinal follow-up will be needed.

• Clinical and Experimental Pediatrics
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• v.49 no.1
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• pp.93-98
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• 2006

Purpose : Ghrelin stimulates the secretion of growth hormone and other pituitary hormones, and has orexigenic effects. It may have a physiologic role in fetal and neonatal growth. Leptin secreted by the adipocytes reflects fat mass in infants as well as adults. The aim of this study was to evaluate the relation of cord blood ghrelin and leptin levels to body weight(BW), body mass index(BMI), insulin-like growth factor-I(IGF-I) and insulin-like growth factor binding protein-3(IGFBP-3) levels in appropriate for gestational age(AGA) newborns. Methods : Sixty healthy AGA newborns(31 males and 29 females, gestational age[GA] 34-42 weeks) were included in this study, whose BW and BMI were measured at delivery. Umbilical cord venous blood samples were withdrawn, and ghrelin and leptin were measured by radioimmunoassay. Cord blood IGF-I and IGFBP-3 were determined by immunoradiometric assay. Results : The mean levels of ghrelin were inversely correlated with BW(r=-0.29, P<0.05) and GA (r=-0.28, P<0.05), but were not affected by gender. The mean levels of leptin levels showed positive correlation with BW(r=0.44, P<0.01), GA(r=0.36, P<0.01), and BMI(r=0.28, P<0.05). The leptin levels of females were higher than those of males. There was no gender difference in leptin levels in neonates under GA 37 weeks. However, the leptin levels of females were higher than those of males (P<0.01) in newborns with GA 37 weeks or over. There was no correlation between ghrelin and leptin levels. Ghrelin and leptin levels showed no relations to cord blood IGF-I and IGFBP-3 levels. Conclusion : These data suggest that cord blood ghrelin may have an inverse correlation with BW in AGA newborns, and leptin levels are positively correlated with BW and fat mass. Further study of ghrelin concentrations in cord blood is necessary to elucidate the physiological and pathological roles of ghrelin during the fetal and neonatal periods.

• Biomedical Science Letters
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• v.10 no.3
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• pp.203-210
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• 2004

It has been reported that glomerulosclerosis mediated by the dysfunction of mesangial cells and insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known the effect of high glucose on IGF-I, -II secretion, IGF-I receptor, and IGFBPs expression in the mesangial cells. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and oxidative stress in mesangial cells. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion and mRNA expression (P<0.05), which was blocked by PKC inhibitor (staurosporine, 10/sup -8/ M) and antioxidant (N-acetyl cystein, 10/sup -5/ M). High glucose decreased IGFBP-1 and -2 expression but increased IGFBP-5 expression. These alteration of IGFBPs by high glucose was also prevented by staurosporine and NAC, suggesting the role of PKC and oxidative stress. Indeed, high glucose increased PKC activity. Furthermore, high glucose-induced increase of lipid peroxide (LPO) formation was blocked by PKC inhibitors. In conclusion, high glucose alters IGF system via PKC-oxidative pathways in mesangial cells.

• Asian-Australasian Journal of Animal Sciences
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• v.12 no.7
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• pp.1135-1141
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• 1999

A large number of investigations have shown that changes in nutritional condition affect endocrine status in avian species. Herein, recent findings including novel peptides discovered by the development of the techniques in the field of molecular biology have been reviewed. The insulin-like growth factors (IGF-I and IGF-II) found in chickens have been characterized and shown to be 70 and 66 amino acid polypeptides, respectively. Plasma IGF-I level is very responsive to nutrition, Le. varying dietary proteins and energy intakes, and food restriction. Plasma IGF-II concentration is altered by nutritional deprivation to a much smaller extent than plasma IGF-I concentration. Almost all of the serum and tissue IGFs are found in a complex composed of IGF and IGF-binding protein (IGFBP). In the chicken plasma, the major IGFBP differs from that in mammalian plasma. The proglucagon mRNA encodes glucagon and two glucagon-like peptides (GLP-I and GLP-2). The intracerebroventricular administration of GLP-l strongly decreased food intake of chicks, and it was indicated that the inhibition of food intake by GLP-l was associated with neuropeptide Y, which is one of the neurotransmitters reported to enhance food intake.