• Korean Journal of Veterinary Research
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• v.46 no.2
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• pp.97-105
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• 2006

All-trans retinoic acid (AtRA) induces growth inhibition and apoptosis in a variety of tumer cells, including MCF-7 cells. Insulin-like growth factors (IGFs) system has been reported to be associated with the development of cancer. Although MCF-7 cell with AtRA is to be the major stimulus for the cell growth and apoptosis, the mechanism of insulin-like growth factor-I (IGF-I)/insulin-like growth factor binding protein-3 (IGFBP-3) system remains to be elucidated. Thus, this study was conducted to the effect of AtRA on the gene expression and level of IGF-I and IGFBP-3. In addition, we investigated the involvement of PKC-${\delta}$ on the IGF-I and IGFBP-3 secretion in MCF-7 cell. AtRA(${\geq}10^{-7}M$) decreased the IGF-1 secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cells. Especially, the treatment of AtRA at 72 hours caused a significant reduction in the IGF-I secretion and mRNA expressions but increment in IGFBP-3 secretion and mRNA expressions (p < 0.05). $10^{-7}M$ AtRA activated PKC-${\delta}$ that is one among PKC-$\iota$, ${\alpha}$, ${\lambda}$ and ${\delta}$ in MCF-7 cell. Rotllerin, a PKC-${\delta}$ inhibitor, blocked AtRA-induced inhibition of the IGF-I and mRNA expressions, and increase of lGFBP-3 and mRNA expressions in MCF-7 cell. Together, AtRA inhibited the IGF-I secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cell. Furthermore, AtRA-induced alteration of IGF-I, IGFBP-3 secretion, and the gene expressions were mediated via PKC-${\delta}$ activity.

• 대한생식의학회:학술대회논문집
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• 1995.12a
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• pp.70.1-70.1
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• 1995

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.3
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• pp.379-384
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• 2010

The principal objective of this experiment was to determine the effects of dietary betaine on IGF-I, IGFBP-3 and IGFBP-1 secretion and IGF-I mRNA gene expression in the serum and liver of laying hens. A total of 72 ISA-Brown laying hens were fed with four different levels of betaine (0, 300, 600, 1,200 ppm) based on a corn-soybean meal diet containing 2,800 kcal/kg of metabolizable energy (ME) and 16% crude protein (CP) for four weeks. The results indicated significantly higher serum and liver IGF-I concentrations in the laying hens fed with 600 and 1,200 ppm betaine (p<0.05) compared to controls. IGF-I gene expression in liver showed a statistically correlated increase in 600 and 1,200 ppm betaine-fed groups as compared to the controls (p<0.05). Serum IGFBP-3 concentrations were elevated significantly in the groups fed 600 ppm of betaine. However, the secretion of IGFBP-1 in the liver of laying hens fed on 600 and 1,200 ppm of betaine was significantly lower than in the controls (p<0.05). The results of this experiment showed that dietary betaine supplementation plays a pivotal role in changes of the IGFs system in laying hens.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.157-162
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• 2013

Insulin-like growth factor binding proteins (IGFBPs) are important components of insulin growth factor (IGF) signaling pathways. One of the binding proteins, IGFBP-5, enhances the actions of IGF-1, which include the enhanced proliferation of smooth muscle cells. In the present study, we examined the expression and the biological effects of IGFBP-5 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The levels of IGFBP-5 mRNA and protein were found to be higher in the VSMC from SHR than in those from WKY. Treatment with recombinant IGFBP-5-stimulated VSMC proliferation in WKY to the levels observed in SHR. In the VSMCs of WKY, incubation with angiotensin (Ang) II or IGF-1 dose dependently increased IGFBP-5 protein levels. Transfection with IGFBP-5 siRNA reduced VSMC proliferation in SHR to the levels exhibited in WKY. In addition, recombinant IGFBP-5 significantly up-regulated ERK1/2 phosphorylation in the VSMCs of WKY as much as those of SHR. Concurrent treatment with the MEK1/2 inhibitors, PD98059 or U0126 completely inhibited recombinant IGFBP-5-induced VSMC proliferation in WKY, while concurrent treatment with the phosphatidylinositol-3 kinase inhibitor, LY294002, had no effect. Furthermore, knockdown with IGFBP-5 siRNA inhibited ERK1/2 phosphorylation in VSMC of SHR. These results suggest that IGFBP-5 plays a role in the regulation of VSMC proliferation via ERK1/2 MAPK signaling in hypertensive rats.

• Clinical and Experimental Pediatrics
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• v.51 no.12
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• pp.1329-1335
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• 2008

Purpose : This study aimed to determine the best cutoff line for insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 to discriminate between growth hormone deficiency (GHD) patients and the control group. Methods : Two hundred thirty subjects with normal controls (129 boys and 101 girls, aged 7-15 years), 14 patients with complete GHD (12 boys and 2 girls), and 17 patients with partial GHD (9 boys and 8 girls) were studied. IGF-I serum concentrations were measured by radioimmunoassay (RI), and IGFBP-3 concentrations were measured by immunoradiometric assay (IRMA). Results : The receiver operating characteristic (ROC) plot analysis showed that the best IGF-I and IGFBP-3 cutoff line was at -1 standard deviation (SD). By comparing IGF-I serum levels of GHD children within 1 SD of normal control, we determined the sensitivity (S) (87.5-100%) and specificity (Sp) (80-84.6%) according to the age group. For IGFBP-3, we determined the following values: S (58.7-85.7%) and Sp (79.2-85.5%). Eleven of 14 patients with complete GHD (78.5%) and 16 of 17 patients with partial GHD (94.1%) had IGF-I concentrations equal to or below -1 SD of the control group mean. Ten of 12 complete GHD children (83.3%) and 13 of 17 partial GHD children (76.5%) had IGFBP-3 concentrations equal or below -1 SD of the control group mean. Conclusion : We conclude that the measurement of IGF-I and IGFBP-3 concentrations might provide essential supplementary data in the diagnostic evaluation of patients with GHD. Our results support the need to use cutoff lines based on below -1 SD of the control.

• Childhood Kidney Diseases
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• v.3 no.2
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• pp.109-116
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• 1999

Purpose: Insulin-like growth factor(IGF)-I and -II are peptide growth factor whose activity is modulated by interaction with the family of six IGF-binding proteins(IGFBPs). IGF-I is detected in rat kidney and has metabolic and growth effects. This study was designed to examine temporal expression of IGFBPs in kidney during renal development and postischemic regeneration in rat. Method: The expression of IGFBPs in kidney during renal development from 15th day of gestation to adult life by using Northern blot analysis. We also examined the renal IGF-IGFBP axis in uremic rat by using Northern blot and immunohistochemistry. Results: The mRNA of IGFBP-1 and -3 were not or barely detected in fetal stages. However, the mRNA level of IGFBP-1 and -3 were increased gradually from day 7 after birth to adult. In contrast, the mRNA of IGFBP-2 and -5 were highly expressed in fetal stages and maintained almost same levels until day 7 (IGFBP-2) or day 30 (IGFBP-5) after birth, then their levels decreased markedly. The mRNA of IGFBP-4 were expressed moderately in fetal kidney and increased gradually after birth. Interestingly, the mRNA of IGFBP-1 and-4 were induced up to 3-5 fold during maximum regeneration period and were recovered to normal levels after acute ischemic injury. In contrast, the mRNA level of IGFBP-3 and-IGFBPrP-1 were decreased slightly at 1 day after ischemic injury, then recovered to normal level during maximum regeneration period. Conclusion: There were differential expressions of IGFBPs in kidney that can modulate IGF action on developing, differentiating, maintaining, and regenerating renal structure and function.

• Clinical and Experimental Pediatrics
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• v.48 no.11
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• pp.1172-1178
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• 2005

Purpose : Childhood Obesity is increasing throughout the world, and it is known to incur many diseases especially in later life such as diabetes and cardiovascular disorders. The purpose of this study was to investigate the association between obesity and insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3(IGFBP-3) and know if these factors are useful in predicting cardiovascular diseases. Methods : The study group consisted of 64 moderate and severe obese adolescents and the controls were normal adolescents of the same age. body mass index(BMI) was calculated by height and weight; systolic and diastolic blood pressure was measured at resting state. After 10-hour fasting period, blood cholesterol, triglyceride, high density lipoprotein(HDL) cholesterol, low density lipoprotein(LDL) cholesterol, glucose, insulin, free fatty acid, IGF-I and IGFBP-3 were measured. Results : Insulin was significantly higher in the obese adolescent group than the control group(obese group $15.6{\pm}7.0{\mu}IU/mL$, P<0.01). IGF-I was also significantly higher in the obese adolescent group than the control group(obese group $498.1{\pm}122.2ng/mL$, P<0.05). In addition, IGFBP-3 was significantly higher in the obese adolescent group than the control group(obese group $3,777{\pm}4,721ng/mL$, P<0.05). Insulin showed significantly positive correlation with BMI(r=0.3944) and obesity index(r=0.34). IGFBP-3 were significantly correlated with obesity index(r=0.419), diastolic blood pressure (r=0.264) and BMI(r=0.247). Insulin resistance index significantly positive correlation with BMI(r=0.595), blood triglycerid level(r=0.515) and obesity index(r=0.469). Conclusion : Serum insulin, insulin resistance index, IGF-I and IGFBP-3 levels may be useful to predict cardiovascular diseases in adolescent obesity.

• Journal of Biosystems Engineering
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• v.38 no.2
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• pp.129-137
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• 2013

Purpose: Modeling has been used for elucidating the mechanism of complex biosystems. In spite of importance and uniqueness of adolescent calcium (Ca) metabolism characterized by a threshold Ca intake, its regulatory mechanism has not been covered and even not proposed. Hence, this study aims at model-based proposing potential mechanisms regulating adolescent Ca metabolism. Methods: Two different hypothetic mechanisms were proposed. The main mechanism is conceived based on Ca-protein binding which induces renal Ca filtration, while additional mechanism assumed that active renal Ca re-absorption regulated Ca metabolism in adolescents. Mathematical models were developed to represent the proposed mechanism and simulated them whether they could produce adolescent Ca profiles in serum and urine. Results: Simulation showed that both mechanisms resulted in the unique behavior of Ca metabolism in adolescents. Based on the simulation insulin-like growth factor-1 (IGF-1) is suggested as a potential regulator because it is related to both growth, a remarkable characteristic of adolescence, and Ca metabolism including absorption and bone accretion. Then, descriptive modeling is employed to conceptualize the hypothesized mechanisms governing adolescent Ca metabolism. Conclusions: This study demonstrated that modeling is a powerful tool for elucidating an unknown mechanism by simulating potential regulatory mechanisms in adolescent Ca metabolism. It is expected that various analytic applications would be plausible in the study of biosystems, particularly with combination of experimental and modeling approaches.

• KSBB Journal
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• v.18 no.4
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• pp.329-334
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• 2003

The present study was aimed at investigating the regulatory mechanism in tissue-specific expression of insulin-like growth factor-I (IGF-I) gene. The expression of IGF-I gene was determined by a solution hybridization/RNase protection assay using total RNA prepared from rat liver or brain of various ages. The levels of IGF-I transcripts were increased in liver gradually after birth, but decreased in brain. By using an oligonucleotide (FRE) corresponding to the C/EBP binding site of the rat IGF-I exon 1, multiple forms of C/EBP${\alpha}$ and C/EBP${\beta}$ proteins, which have DNA-binding activity, were detected in the rat liver or brain. Western immunoblot and southwestern analyses show that p42$\^$C/EBP${\alpha}$/, p38$\^$C/EBP${\alpha}$/, p35$\^$C/EBP${\alpha}$/, p38$\^$C/EBP${\beta}$/, and p35$\^$C/EBP${\beta}$ form specific complexes with the IGF-I exon 1 oligonucleotide in liver nuclear extract and that p42$\^$C/EBP${\alpha}$/ and p38$\^$C/EBP${\beta}$/ form complexes in brain. These data suggest that the formation of FRE-C/EBP isoform complexes may play important roles in the tissue-specific regulation of IGF-I gene expression.

• 대한예방의학회:학술대회논문집
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• 2004.10a
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• pp.34.1-34.1
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• 2004