• Tuberculosis and Respiratory Diseases
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• 제47권5호
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• pp.618-628
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• 1999

연구배경: 세포성장은 세포증식과 세포죽음의 균형에 의해 이루어 진다. 세포성장에 관여하는 여러 growth factor증 IGF-I은 IGF-IR와 결합하여 세포증식을 유발하는 mitogen으로 알려져 있다. 또한 IGF-I에 결합하는 IGFBPs중에 IGFBP-3는 혈액내에 가장 많은 carrier protein으로, IGF-I과 결합하여 IGF-I의 세포증식 효과를 증가 혹은 억제시킨다. 방 법: 3T3 fibroblast 세포를 이용하여 IGF-I과 IGF-IR transcripts를 northern blot으로 확인하고, IGF-I에 의한 mitogenic effect를 MTT assay 및 $^3H$-thymidine incorporation test로 관찰하고, IGF-I의 receptor인 IGF-IR의 활성화를 보기 위해 intracellular $\beta$-subunit의 tyrosine kinase domain의 phosphorylation을 western blot으로 관찰하였다. 또한 IGFBP-3가 3T3 세포에서 mitogenic effect에 미치는 영향을 보기 위해 anti-IGFBP-3와 ${\alpha}IR_3$을 단독 및 병용투여하여 관찰하였다. 결 과: 3T3 세포는 IGF-I와 IGF-IR의 mRNA expression을 보였으며, IGF-I을 투여시 IGF-IR의 intracelluar cytoplasmic protein인 $\beta$-subunit의 tyrosine kinase domain을 phosphorylation시켜 활성화시키며, 5%, 1% serum-containing media에서 세포증식을 보였으나, serum-free media에서는 세포증식을 보이지 않았다. 또한 anti-IGFBP-3 투여와 ${\alpha}IR_3$과 anti-IGFBP-3를 병용투여시는 세포종식이 각각 2배이상 증가하였으나, ${\alpha}IR_3$을 4시간 전처치후 ${\alpha}IR_3$과 anti-IGFBP-3를 병용투여시는 anti-IGFBP-3에 의한 세포종식이 보이지 않은 것으로 보아 IGF -I/IGFBP-3 결합에서 분리되는 free IGF-I어l 의해 세포증식이 유도된 것으로 생각된다. 결 론: IGF-I은 IGF-IR를 phosphorylation시켜 mitogenic effect를 보이며, IGFBP-3는 IGF-I의 mitogenic effect를 억제하는 것으로 생각된다.

• Molecules and Cells
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• 제41권10호
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• pp.909-916
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• 2018

In pancreatic ${\beta}$ cells, glucose stimulates the biosynthesis of insulin at transcriptional and post-transcriptional levels. The RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1), also named hnRNP I, acts as a critical mediator of insulin biosynthesis through binding to the pyrimidine-rich region in the 3'-untranslated region (UTR) of insulin mRNA. However, the underlying mechanism that regulates its expression in ${\beta}$ cells is unclear. Here, we report that glucose induces the expression of PTBP1 via the insulin receptor (IR) signaling pathway in ${\beta}$ cells. PTBP1 is present in ${\beta}$ cells of both mouse and monkey, where its levels are increased by glucose and insulin, but not by insulin-like growth factor 1. PTBP1 levels in immortalized ${\beta}$ cells established from wild-type (${\beta}IRWT$) mice are higher than levels in ${\beta}$ cells established from IR-null (${\beta}IRKO$) mice, and ectopic re-expression of IR-WT in ${\beta}IRKO$ cells restored PTBP1 levels. However, PTBP1 levels were not altered in ${\beta}IRKO$ cells transfected with IR-3YA, in which the Tyr1158/1162/1163 residues are substituted with Ala. Consistently, treatment with glucose or insulin elevated PTBP1 levels in ${\beta}IRWT$ cells, but not in ${\beta}IRKO$ cells. In addition, silencing Akt significantly lowered PTBP1 levels. Thus, our results identify insulin as a pivotal mediator of glucose-induced PTBP1 expression in pancreatic ${\beta}$ cells.

• Clinical and Experimental Pediatrics
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• 제48권11호
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• pp.1172-1178
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• 2005

목 적 : 소아 비만은 전세계적으로 증가하고 있는 추세이며, 신체적으로나 정신적으로 장애를 일으킨다. 특히 고혈압, 관상동맥질환, 당뇨병 등의 성인병이 문제가 되고 있다. 이에 비만 청소년에서 혈중 인슐린, 인슐린저항지수, 유리 지방산, IGF-I, IGFBP-3를 측정하였고, 심혈관 질환으로 진행할 수 있는 위험인자로 유용한지 알아보기 위해 본 연구를 실시하였다. 방 법 : 64명의 중등도 이상의 비만 청소년를 대상군으로 하였고, 같은 연령의 정상 청소년 20명을 대조군으로 하였다. 신장, 체중을 이용하여 비만도와 체질량지수를 산출하였고, 안정된 상태에서 수축기, 이완기 혈압을 측정하였다. 10시간 이상 금식 후 총 콜레스테롤, 중성지방, HDL 콜레스테롤, LDL 콜레스테롤, AST, ALT, 혈당, 인슐린, 유리지방산, IGF-I, IGFBP-3를 측정하였다. 결 과 : 인슐린은 비만군에서 $15.6{\pm}7.0{\mu}IU/mL$로 정상군보다 유의하게 높았고(P<0.01), 인슐린저항지수도 비만군에서 $64.6{\pm}31.6$으로 정상군보다 유의하게 높았다(P<0.01). IGF-I은 비만군에서 $498.1{\pm}122.2ng/mL$로 정상군보다 유의하게 높았고(P<0.05), IGFBP-3도 비만군에서 $3,777{\pm}4,721ng/mL$로 정상군보다 유의하게 높았다(P<0.05). 인슐린은 체질량지수(r=0.394), 비만도(r=0.304)와 양의 상관관계를 나타냈다. IGFBP-3는 비만도(r=0.419), 이완기 혈압(r=0.264), 체질량지수(r=0.247)와 양의 상관관계를 보였다. 인슐린저항지수는 체질량지수(r=0.595), 혈중 중성지방(r=0.515), 비만도(0.469)와 양의 상관관계를 나타냈다. 결 론 : 비만 청소년에서 혈중 인슐린, 인슐린저항지수, IGF-I, IGFBP-3가 증가하였다. 청소년 비만에서 이들 검사는 심혈관질환으로의 진행을 예측하는데 유용하리라 생각한다.

• 대한의생명과학회지
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• 제12권3호
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• pp.217-224
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• 2006

It has been reported that the dysfunctions of podocytes are associated with the development of diabetic nephropathy. In addition, insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I, -II secretion, and IGF binding proteins (IGFBPs) expression in the podocytes. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and mitogen activated protein kinases (MAPKs) in podocytes. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion (P<0.05), which was blocked by SB 203580 (a p38 MAPK inhibitor) but not by PD 98059 (a p44/42 MAPK inhibitor). In addition, high glucose-induced stimulation of IGFs was blocked by bisindolylmaleimide I and staurosporine (protein kinase C inhibitors). High glucose also increased IGFBP-l expression, which was blocked by bisindolylmaleimide I and SB 203580. In conclusion, high glucose alters IGFs secretion and IGFBP expression via PKC and p38 MAPK pathways in podocytes.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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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.

• Childhood Kidney Diseases
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• 제3권2호
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• pp.109-116
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• 1999

목적 : Insuln-like growth factor(IGF)-I및 -II는 성장인자로 일군의 IGF-binding protein(IGFBP)에 의하여 그 작용이 조절된다. IGF-I은 백서 신장에서 발견되고 대사효과와 성장효과를 갖고 있다. 이번 연구는 백서에서 신장발육과 허혈성 신손상 후 재생과정 동안에 IGFBP의 발현이 변화하는지를 보고자 한다. 방법 : 태생 15주부터 성숙 할때까지 백서 신장에서 IGFBP 발현의 변화를 알아보기 위해 Northern blotting을 시행하였고, 급성신부전 백서의 신장에서 IGF-IGBP axis의 변화를 보기 위해 Northern blotting과 Immunohisto-chemistry를 이용하였다. 결과 : IGFBP-1과 -3는 태생기에는 거의 발현되지 않다가 출생 후 7일째부터 성숙이 끝날 때까지 점진적으로 증가하였다. 반면에 IGFBP-2와 -5는 태생기에 많이 발현되고, IGFBP-2는 출생 후 7일째까지 IGFBP-5는 30일째까지 높은 농도를 유지하다가 급격히 감소하였다. 한편 IGFBP-4는 태생기에 중등도로 발현되는데 출생 후 증가하기 시작하여 7일째 가장 많이 발현되다가 급격히 감소하였다. 신손상 후 IGFBP의 변화를 보면 IGFBP-1과 -4는 재생기간 동안 3-5배 증가되다가 정상으로 회복된 반면 IGFBP-3와 IGFBP Related Protein-1(IGFBPrP-1) 은 신손상 1일째에는 약간 감소하다가 그후 증가하여 정상보다 약간 높은 수준을 유지하였다. 결론 : 백서 신장에서 신장구조나 기능의 발달, 분화 및 재생에 대한 IGF의 작용을 조절할 수 있는 IGFBP 발현에 현저한 변화가 있었다.

• Asian-Australasian Journal of Animal Sciences
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• 제21권3호
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• pp.309-313
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• 2008

The insulin-like growth factor binding protein 3 (IGFBP3) has been investigated as a candidate gene for growth promoting effects in beef cattle and a modulator of IGF bioactivity. Previously, we have reported twenty two sequence variants discovered in Korean native cattle (Hanwoo). In this study, we examined the association between gene-specific polymorphisms of IGFBP3 and cold carcass weight (CW) and marbling score (MS) among Korean native cattle. Among twenty two polymorphisms, four common polymorphic sites (-854G>C, -100G>A, +421G>T and +3863C>A) were genotyped in our beef cattle (n = 437). Statistical analysis revealed that one common polymorphism in the promoter region (-854G>C) showed putative associations with MS (p = 0.03). IGFBP3 variation/haplotype information analyzed in this study will provide valuable information into strategies for the production of a commercial line of beef cattle.

• BMB Reports
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• 제35권2호
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• pp.186-193
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• 2002

The acid-bible subunit (ALS) associates with the insulinlike growth factor (IGF)-I or II, and the IGF binding protein-3 (IGFBP-3) in order to form a 150-kD complex in the circulation. This complex may regulate the serum IGFs by restricting them in the vascular system and promoting their endocrine actions. Little is known about how ALS binds to IGFBP3, which connects the IGFs to ALS. Xenopus oocyte was utilized to study the function of ALS in assembling IGFs into the ternary complexes. Xenopus oocyte was shown to correctly translate in vitro transcribed mRNAs of ALS and IGFBP3. IGFBP3 and ALS mRNAs were injected in a mixture, and their products were immunoprecipitated by antisera against ALS and IGFBP3. Contrary to traditional reports that ALS interacts only with IGF-bound IGFBP3, this study shows that ALS is capable of forming a binary complex with IGFBP3 in the absence of IGF When cross-linked by disuccinimidyl suberate, the band that represents the ALS-IGFBP3 complex was evident on the PAGE. IGFBP3 movement was monitored according to the distribution between the hemispheres. Following a localized translation in the vegetal hemisphere, IGFBP3 remained in the vegetal half in the presence of ALS. However, the mutant IGFBP3 freely diffused into the animal half, despite the presence of ALS, which is different from the wild type IGFBP3. This study, therefore, suggests that ALS may play an important role in sequestering IGFBP3 polypeptides via the intermolecular aggregation. Studies using this heterologous model will lead to a better understanding of the IGFBP3 and ALS that assemble into the ternary structure and circulate the IGF system.

• Tuberculosis and Respiratory Diseases
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• 제50권5호
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• pp.549-556
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• 2001

연구배경 : 세포성장에 관여하는 여러 growth factor중 IGF-I은 IGF-IR와 결합하여 세포증식을 유발하는 mitogen으로 알려져 있다. 대부분의 정상세포 및 암세포는 IGFBPs을 분비하는데 이들은 IGF-I과 결합하여 IGF-I의 세포증식 효과를 증가 혹은 억제시킨다. 마우스 폐암세포주 (3LL)에서 IGF-I이 세포성장에 미치는 효과를 보고, 3LL 세포에서 분비되는 IGFBP을 추출 확인하고, IGFBPs이 세포 성정에 미치는 영향을 관찰하였다. 방 법 : 마우스 폐암세포주 (3LL)를 이용하여, IGF-I을 투여하여 세포성장을 MTT assay로 측정하였고, 3LL에서 분비되는 IGFBP을 추출하여 Western ligand blot 및 western immunoblot으로 확인하였다. 또한 분비된 IGFBP이 세포성장에 미치는 영향을 보기위해, anti-IGFBP antibody을 첨가하여 이의 기능을 억제하여 세포성장에 관한 기능을 관찰하였다. 결 과 : IGF-I은 serum free media에서 3LL 세포성장을 증가시켰다. 3LL 세포는 IGFBP-4를 생성하는 것을 확인하였고, anti-IGFBP-4 antibody를 첨가시 세포성장이 증가된 소견이 관찰되어 IGFBP-4는 세포증식을 억제하는 기능을 가지고 있음을 간접적으로 알 수 있었다. 결 론 : 이상의 실험 결과로 3LL 마우스 폐암세포에서 IGF-I은 세포성장을 증가시키며, 3LL에서 생성된 IGFBP-4는 세포증식을 억제하는 기능을 가지고 있다는 것을 관찰하였다. 향후 IGF-I과 IGFBPs이 암 성장에 미치는 기전과 임상적 적용에 대한 연구가 필요하리라 생각된다.

• 한국가정과학회지
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• 제9권1호
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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.