• Title/Summary/Keyword: Insulin-like growth factor system

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Hormonal Regulation of Insulin-Like Growth Factor Binding Protein Secretion by a Bovine Mammary Epithelial Cell Line

  • Kim, W.Y.;Chow, J.C.;Hanigan, M.D.;Calvert, C.C.;Ha, J.K.;Baldwin, R.L.
    • Asian-Australasian Journal of Animal Sciences
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    • v.10 no.2
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    • pp.233-239
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    • 1997
  • A mammary epithelial cell line (MAC-T) established as a model for lactation was utilized to identify and characterize effects of various hormones upon insulin-like growth factor binding protein secretion. Ligand and immunoblot analyses of conditioned media indicated that insulin-like growth factor binding protein-2 was secreted by MAC-T cells. Insulin-like growth factor-I stimulated insulin-like growth factor binding protein-2 secretion in a dose-dependent manner, but prolactin and bovine somatotropin did not alter insulin-like growth factor binding protein-2 secretion. Insulin increased and cortisol decreased insulin-like growth factor binding protein-2 secretion. Effects of insulin-like growth factor-I on insulin-like growth factor binding protein-2 secretion support previous studies using primary cultures of bovine mammary cells and bovine fibroblasts. Effects of cortisol and insulin on insulin-like growth factor binding protein-2 secretion may be explained by changes in protein synthesis. In addition, supraphysiological doses of insulin can cross-react with the insulin-like growth factor-I receptor and stimulate insulin-like growth factor binding protein-2 secretion. MAC-T cells provide a model system to study mechanisms that regulate local insulin-like growth factor-I bioactivity.

The roles of PKC-δ on the regulation of insulin-like growth factor(IGF)-I and insulin-Like growth factor binding protein-3 secretion by all-trans retinoic acid in MCF-7 cell (MCF-7 cell에서 all-trans retinoic acid에 의한 insulin-like growth factor-I와 insulin-like growth factor binding protein-3 분비조절에 있어서 PKC-δ의 역할)

  • Lee, Sun-Mi;Kim, Sang-Hoon;Choi, Kwang-Soo;Kang, Chang-Won
    • 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.

Growth Stimulation and Inhibition of Differentiation of the Human Colon Carcinoma Cell Line Caco-2 with an Anti-Sense Insulin-Like Growth Factor Binding Protein-3 Construct

  • YoonPark, Jung-Han
    • BMB Reports
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    • v.32 no.3
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    • pp.266-272
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    • 1999
  • The insulin-like growth factor (IGF) system consisting of IGF-I, IGF-II, IGF-receptors, and IGF-binding proteins (IGFBP) regulates the proliferation of a variety of cancer cell types. To examine whether a decrease in endogenous IGFBP-3 stimulates proliferation or inhibits differentiation, Caco-2 cells, a human colon adenocarcinoma cell line, were stably transfected with an anti-sense IGFBP-3 expression construct or pcDNA3 vector as control. Accumulation of IGFBP-3 mRNA and secretion of IGFBP-3 into serum-free conditioned medium, 9 days after plating, were significantly lower in Caco-2 cell clones transfected with anti-sense IGFBP-3 cDNA compared to the controls. The anti-sense clones grew at a similar rate to the controls for 8 days after plating, but achieved a higher final density between days 10 and 12. The levels of sucrase-isomaltase mRNA, a marker of enterocyte differentiation of Caco-2 cells, were lower in the anti-sense clones examined on day 9. In conclusion, proliferation of Caco-2 cells can be stimulated by lowering endogenously-produced IGFBP-3.

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Protein variation and involvement of insulin-like growth factor during embryonic development in the olive flounder Paralichthys olivaceus

  • Kim, Kang-Woong;Nam, Taek Jeong;Choi, Youn Hee
    • Fisheries and Aquatic Sciences
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    • v.21 no.2
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    • pp.4.1-4.5
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    • 2018
  • Insulin-like growth factors (IGFs), along with IGF-binding protein and IGF receptor, are well-known regulators in the growth and survival of vertebrates. In this study, we investigated the involvement of IGFs and protein variation during embryonic development of the olive flounder (Paralichthys olivaceus). Morphological stages were divided into six main developments as blastula, gastrula, cephalization, cranial regionalization, tail lift, and hatch. During embryonic development, protein variation was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray ionization quadrupole time-of-flight mass spectrometry/mass spectrometry. In addition, the mechanism of signaling of IGF-I receptor was examined using immuno-blot analysis. We found marked changes in protein expression at four stages of embryonic development and identified proteins as belonging to the vitellogenin 2 family. As development progresses, expression of IGF-II, phosphotyrosine, and phospho-Akt increased, while expression of growth factor receptor-bound protein 2 (GRB2) and one of guanine-nucleotide-binding proteins (Ras) decreased. These results provide basic information on the IGF system in the embryonic development of the olive flounder.

Knock-in Vector for Expression of Insulin-like Growth Factor 1 on the Bovine β-casein Gene Locus (소 β-casein 유전자 영역에서 소 Insulin-like Growth Factor 1을 생산하기 위한 Knock-in Vector)

  • Kim, Sang Young;Park, Da Som;Kim, Se Eun;Koo, Deog-Bon;Kang, Man-Jong
    • Reproductive and Developmental Biology
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    • v.41 no.3
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    • pp.51-55
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    • 2017
  • The production of therapeutic protein from transgenic domestic animal is the major technology of biotechnology. Insulin-like growth factor-1 (IGF-1) is known to play an important role in the growth of the animal. The objective of this study is construction of knock-in vector that bovine IGF-1 gene is inserted into the exon 7 locus of ${\beta}$-casein gene and expressed using the gene regulatory DNA sequence of bovine ${\beta}$-casein gene. The knock-in vector consists of 5' arm region (1.02 kb), bIGF-1 cDNA, CMV-EGFP, and 3' arm region (1.81 kb). To express bIGF-1 gene as transgene, the F2A sequence was fused to the 5' terminal of bIGF-1 gene and inserted into exon 7 of the ${\beta}$-casein gene. As a result, the knock-in vector is confirmed that the amino acids are synthesized without termination from the ${\beta}$-casein exon 7 region to the bIGF-1 gene by DNA sequence. These knock-in vectors may help to create transgenic dairy cattle expressing bovine bIGF-1 protein in the mammary gland via the expression system of the bovine ${\beta}$-casein gene.

Effects of Dietary Betaine on the Secretion of Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Protein-1 and -3 in Laying Hens

  • Choe, H.S.;Li, H.L.;Park, J.H.;Kang, C.W.;Ryu, Kyeong Seon
    • 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.

Changes of Insulin-like Growth factor-I, II and IGF-Binding Protein-3 on Fasting and Postprandial state in Diabetes (당뇨환자의 식사 전후에 따른 혈중 Insulin-like growth factor(IGF-I), IGF-II 및 Insulin-like growth factor binding proteins(IGFBP)-3의 변화)

  • Heo, Young-Ran;Kang, Chang-Won;Cha, Youn-Soo
    • 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.

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Effects of Glucose on Insulin-like Growth Factor Binding-5 Expression in Human Fibroblasts. (사람의 섬유아세포에서 Glucose 농도가 Insulin-like Growth Factor Binding Protein-5의 발현에 미치는 영향)

  • Ryu, Hye-Young;Hwang, Hye-Jung;Kim, In-Hye;Ryu, Hong-Soo;Nam, Taek-Jeong
    • 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.