• Journal of Veterinary Clinics
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• v.20 no.3
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• pp.263-273
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• 2003

This study was carried out to investigate the effects of the Korean Safflower (Carthamus inctorius L) seed powder on serum level of hormones and trabecula area during the recovery from osteoporosis induced ovariectomized rats. Four month-old rats were ovariectomized (OVX), remained untreated for 8 weeks, and were subsequently administered safflower seed (0.03 g/kg) every other day 30 for days. We examined the effects of treated safflower seed every 10 days on ovariectomy-related changes in Insulin-like Growth Factors, Insulin-like Growth Factor binding protein-3 (IGFBP-3), Estrogen, Bone-specific alkaline phosphotase, Calcium, and Phospotase in the serum, and also histomorphology of the proximal fibula metaphysis and femur/body weight rate. Ten and 20 days after safflower seed treatment in OVX rats, serum levels of IGF-I, -II and IGFBP-3 were not different from the Sham and OVX groups. In 30 days, serum levels of IGF-I,-II and IGFBP-3 were higher after safflower seed treatment in OVX rats as compared to the other two groups (p<0.05). Bone alkaline phosphatase levels were increased through safflower seed treatment in OVX rats compared to the other two groups in 30 days. There were no differences between OVX and safflower seed treated OVX rats in serum levels of estrogen and femur/body weight rate, but estrogen levels for the sham group were higher than for the other two groups. The safflower seed is increased to serum levels of IGFs, IGFBP-3 and BALP of osteoporosis induced by ovariectomized rats. Thus, we conclude that the safflower seed is a possible role for improvement of osteoporosis induced-ovariectomized rats.

• 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.

• Proceedings of the Korean Nutrition Society Conference
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• 1999.05b
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• pp.39-40
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• 1999

• Journal of Life Science
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• v.23 no.11
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• pp.1311-1316
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• 2013

Heterogeneous nuclear ribonucleoprotein L (hnRNP L) is a major pre-mRNA binding protein and it is an abundant nuclear protein that shuttles between the nucleus and the cytoplasm. hnRNP L is known to be related to many cellular processes, including chromatin modification, pre-mRNA splicing, mRNA export of intronless genes, internal ribosomal entry site (IRES)-mediated translation, mRNA stability, and spermatogenesis. In order to identify the cellular proteins interacting with hnRNP L, this study performed a yeast two-hybrid screening, using a human liver cDNA library. The study identified insulin-like growth factor binding protein-4 (IGFBP-4) as a novel interaction partner of hnRNP L in the human liver. It then discovered, for the first time, that hnRNP L interacts specifically with IGFBP-4 in a yeast two-hybrid system. The authenticity of this two-hybrid interaction of hnRNP L and IGFBP-4 was confirmed by an in vitro pull-down assay.

• Journal of Life Science
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• v.17 no.9 s.89
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• pp.1224-1231
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• 2007

Insulin-like growth factor-I (IGF-I) and IGF-II have structure like insulin. In contrast to insulin, however, the bioavaility of IGFs is modulated by the IGF-binding protein (IGFBPs). Each of IGFBPs was different with molecular masses, biological characteristics, and immunological properties.. Human fibroblasts secrete IGFBPs that can modify IGF-I action. In diabetes mellitus, the most study of IGF systems have been investigated in insulin-dependent diabetes mellitus, non-insulin-dependent diabetes mellitus, and streptozotocin-in-duced animals in vivo. Recently, a little research regarding the IGFs system has been proposed in por-tion of cell in vitro. In this study, effects of low or high glucose condition on IGFBP-5 in GM10 was investigated. By western blotting analysis, IGFBP-5 level decreased in cells cultured at high glucose, but IGFBP-5 level of mRNA didn't change. IGFBP-5 protease that cleaves IGFBP-5 in conditioned me-dium had was inhibited by EDTA and heparin, like serine protease and metalloprotease. Furthermore, the protease activity was increased in high glucose cultivated condition. In results of gelatin zymog-raphy, molecular weight of proteolytic metalloenzymes was indentified 69-kDa and protease activity was increased in time-dependent manner. Although the mechanism has yet to be determined, IGFBP-5 proteolysis in GM10 cells cultured with high glucose may increase effects of IGFs to decrease the glu-cose level through dissociation of IGFs from IGFBPs. Therefore, we suggest that IGF- I and IGFBPs could be potential models in study of pathophysiology such as diabetes mellitus.

• 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.

• 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.

• Nuclear Engineering and Technology
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• v.12 no.2
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• pp.121-126
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• 1980

Selection methods of well labelled insulin fractions based on two different criteria were compared to establish an efficient low level RIA of insulin and to elucidate the correlation between the immunoreactivity and the charcoal-adsorptivity of the radioiodine labelled insulin. The results indicated that the selection of well labelled insulin fractions by means of a charcoal-adsorption test is inappropriate. Generally, the distribution of radioactivity antibody-bindability, and charcoal-adsorptivity of the labelled insulin was not consistent with each other. Thus. the selection should be carried out for every labelling batch to get the utmost assay reliability by antibody-bindability but not by charcoal-adsorptivity. By using the well selected labelled insulin fractions based on antibody-binding, a correct assay for a reference serum was possible, and by extending the incubation time upto 96 hrs, a sharp dose response curve could be obtained even in the range of below 5 $\mu$U/ml standard insulin doses.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6475-6479
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• 2012

Background: Recent studies have demonstrated an association between insulin growth factor (IGF) and insulin growth factor binding protein-3 (IGFBP-III) serum levels and increased risk for various cancers. However, little information is available on clinical implications of the IGF system in Indian patients with cervical cancer. This study explored associations by analyzing their expression profiles in cervical cancer cases. Materials and Methods: Totals of 50 patients with advanced cervical cancer and 40 healthy controls were enrolled. Human papillomavirus (HPV) and cervical biopsy sample were obtained from all participating women. Circulatory levels were estimated by ELISA and the tissue expression was assessed using RT-PCR and Western blotting. Results: Levels of IGF-I and II showed significant increase whereas IGFBP-III showed significant decline in all patients as compared to controls. Spearman correlation analysis between IGFs and HPV status showed significant correlations. Conclusions: We demonstrated elevated circulating levels and tissue expression of IGF-I and IGF-II in advancer cancer cervix patients, as compared with controls, with a converse trend being apparent for IGFBP-III. In future, associations of the IGF system and clinical outcome of cervical cancer patients in post treatment samples might point to significance in disease mapping as a prognostic marker after validation with a larger patient series.

• BMB Reports
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• v.45 no.6
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• pp.360-364
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• 2012

Uptake of circulating glucose into the cells happens via the insulin-mediated signalling pathway, which translocates the glucose transporter 4 (GLUT4) vesicles from the intracellular compartment to the plasma membrane. Rab GTPases are involved in this vesicle trafficking, where Rab GTPases-activating proteins (RabGAP) enhance the GTP to GDP hydrolysis. TBC1D4 (AS160) and TBC1D1 are functional RabGAPs in the adipocytes and the skeletonal myocytes, respectively. These proteins contain two phosphotyrosine-binding domains (PTBs) at the amino-terminus of the catalytic RabGAP domain. The second PTB has been shown to interact with the cytoplasmic region of the insulin-regulated aminopeptidase (IRAP) of the GLUT4 vesicle. In this study, we quantitatively measured the ${\sim}{\mu}M$ affinity ($K_D$) between TBC1D4 PTB and IRAP using isothermal titration calorimetry, and further showed that IRAP residues 1-49 are the major region mediating this interaction. We also demonstrated that the IRAP residues 1-15 are necessary but not sufficient for the PTB interaction.