• Title/Summary/Keyword: insulin/IGF-1

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Rehmannia Radix(RR) Extracts Inhibit IGF-II Induced VEGF and HIF-1 ${\alpha}$ Expressions in HaCaT Keratinocyte Cells (Rehmannia Radix의 IGF-II로 유도된 HIF-1 ${\alpha}$와 VEGF 발현 억제)

  • Park, Ung;Shin, Yong-Cheol;Ko, Seong-Gyu
    • Journal of Society of Preventive Korean Medicine
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    • v.10 no.2
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    • pp.51-62
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    • 2006
  • Psoriasis is a chronic skin disease characterized by angiogenesis. It has been reported that growth factor as vascular endothelial growth factor(VEGF) and insulin like growth factor(IGF) II are overexpressed in psoriatic epidermis. To investigate the inhibitory effects of IGF-II induced VEGF and HIF-1${\alpha}$ expression by RR extracts, we performed MTS assay, western blots using HaCaT cells. RR extracts significantly reduced IGF-II induced HIF 1${\alpha}$ protein level via MAPK pathway in HaCaT cells. Also, RR extracts inhibited IGF-II induced VEGF mRNA and protein expression levels in the HaCaT keratinocytes. These results suggest that inhibition of HIF-1${\alpha}$ and VEGF expressions by RR extracts contributes to the anti angiogenic effects.

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The Relationship of Repeated Racehorse Simulator Exercise on Plasma Ghrelin and Hormons in Jockeys (반복적인 모형마 운동에 따른 기수의 혈장 그렐린과 호르몬들의 관계)

  • Zhang, Seok-Am
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.4
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    • pp.1756-1762
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    • 2011
  • The aim of the present investigation was to investigate the relationship of repeated racehorse simulator exercise on plasma ghrelin and hormons in fasted jockeys. The fasted jockeys and apprentice jockeys performed $1^{st}$ short distance 1000m, $2^{nd}$ middle distance 1700m and $3^{rd}$ long distance 2300m racehorse simulator exercises, and venous blood samples were obtained before, immediately after. In addition to ghrelin concentration, leptin, insulin, insulin-like growth factor-1 (IGF-1), and cortisol values were measured. Pearson correlation coefficients revealed plasma ghrelin and insulin concentration in apprentice jockeys r=.55 after the $3^{rd}$ exercise. There were relationships between significant relationships (p<.05) between plasma ghrelin and leption concentration in jockeys r=.73, and between plasma ghrelin and cortisol concentration in apprentice jockeys r=.64 before exercise. There was no difference in the ghrelin, leptin, insulin and IGF-1 concentration responses to the consecutive exercise. The IGF-1 and cortisol level showed significant (p<.05)difference between groups. In conclusion, these results suggest that negative energy balance induced by of repeated racehorse simulator exercise elicits a metabolic response with positive relationship in plasma ghrelin and insulin in apprentice jockeys after the $3^{rd}$ exercise.

Effect of Insulin-like Growth Factor-1 on Bone Morphogenetic Protein-2 Expression in Hepatic Carcinoma SMMC7721 Cells through the p38 MAPK Signaling Pathway

  • Xu, Guan-Jun;Cai, Sheng;Wu, Jian-Bing
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1183-1186
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    • 2012
  • Objective: To observe the effect of insulin-like growth factor-1 (IGF-1) on bone morphogenetic protein (BMP)-2 expression in hepatocellular carcinoma SMMC7721 cells. Methods: Cells were divided into blank control, IGF-1, IGF-1 + SB203580, and SB203580 groups. SB203580 was used to block the p38 MAPK signaling pathway. Changes in the expression of BMP-2, p38 MAPK, and phosphorylated p38, MERK, ERK and JNK were determined using reverse transcription polymerase chain reactions (RT-PCR) and Western blot analysis. Results: Protein expression of phosphorylated BMP-2, MERK, ERK, and JNK was significantly up-regulated by IGF-1 compared with the control group ($1.138{\pm}0.065$ vs. $0.606{\pm}0.013$, $0.292{\pm}0.005$ vs. $0.150{\pm}0.081$, $0.378{\pm}0.006$ vs. $0.606{\pm}0.013$, and $0.299{\pm}0.015$ vs. $0.196{\pm}0.017$, respectively; P<0.05). Levels of BMP-2 and phosphorylated MERK and JNK were significantly reduced after blocking of the p38MAPK signaling pathway ($0.494{\pm}0.052$ vs. $0.165{\pm}0.017$, $0.073{\pm}0.07$ vs. $0.150{\pm}0.081$, and $0.018{\pm}0.008$ vs. $0.196{\pm}0.017$, respectively; P<0.05), but such a significant difference was not observed for phosphorylated ERK protein expression ($0.173{\pm}0.07$ vs. $0.150{\pm}0.081$, P>0.05). Conclusion: IGF-1 can up-regulate BMP-2 expression, and p38 MAPK signaling pathway blockage can noticeably reduce the up-regulated expression. We can conclude that the up-regulatory effect of IGF-1 on BMP-2 expression is realized through the p38 MAPK signaling pathway.

Immunohistochemical Staining of Insulin-like Growth Factor-1 in Human Lung Cancer Cells (폐암의 조직학적 형태에 따른 인슐린양 성장인자-1의 면역조직학적 염색의 비교)

  • Park, Ji-Hyun;Kang, Myoung-Jae;Lee, Heung-Bum;Lee, Yong-Chul;Rhee, Yang-Kuen
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.3
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    • pp.324-330
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    • 2000
  • Objective : Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. Multiple molecular changes and growth factor production have been documented in lung cancers, both small cell and non-small cell types. Insulin-like growth factors(IGFs) are important mitogenic and anabolic peptides, both in vivo and in vitro, and are thought to be significant autocrine-paracrine factors involved in normal and malignant cell proliferation. In this study, the degree of expression of IGF-1 on the immunohistochemical staining in human non-small cell lung cancer(NSCLC) cells and small cell lung cancer (SCLC) cells were investigated. Methods : Immunohistochemical staining for IGF-1 was performed in 15 cases of small cell carcinoma, 15 cases of squamous cell carcinoma, 15 cases of adenocarcinoma, and 12 cases of bronchoalveolar carcinoma. Results : The expression of IGF-1 on the immunohistochemical staining significantly increased in NSCLC cells than in SCLC cells. Conclusion : These results suggest the expression of IGF-1 in human lung cancer cells. The immunohistochemical staining of IGF-1 in lung cancer cell lines may assist in the differentiation of NSCLC and SCLC.

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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.

Roles of the Insulin-like Growth Factor System in the Reproductive Function;Uterine Connection (Insulin-like Growth Factor Systems의 생식기능에서의 역할;자궁편)

  • Lee, Chul-Young
    • Clinical and Experimental Reproductive Medicine
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    • v.23 no.3
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    • pp.247-268
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    • 1996
  • It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.

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Cord Blood Adiponectin and Insulin-like Growth Factor-I in Term Neonates of Gestational Diabetes Mellitus Mothers: Relationship to Fetal Growth

  • Sohn, Jin-A;Park, Eun-Ae;Cho, Su-Jin;Kim, Young-Ju;Park, Hye-Sook
    • Neonatal Medicine
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    • v.18 no.1
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    • pp.49-58
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    • 2011
  • Purpose: The purpose of this study was to evaluate the relationship between cord blood adiponectin and insulin-like growth factor (IGF)-I and their effect on fetal growth and insulin resistance in mothers with gestational diabetes mellitus (GDM). Methods: Cord blood adiponectin and IGF-I were compared between mothers with GDM (GDM group, N=53) and controls (non-GDM group, N=101). Neonates were classified into three groups of small for gestational age (SGA, N=26), appropriate for gestational age (AGA, N=97), and large for gestational age (LGA, N=31) by birth weight. The association between cord adiponectin and IGF-I levels was evaluated in relation to maternal and neonatal clinical data. Results: Cord adiponectin was lower in the GDM group than in the non-GDM group (P<0.001). There was no significant difference in cord adiponectin among the SGA, AGA, and LGA groups in the GDM group (P=0.228). The cord adiponectin of AGA in the GDM group was significantly lower than that in the non-GDM group (P<0.001). The most powerful predictor affecting cord adiponectin was the result of maternal 75 g oral glucose tolerance test. The cord IGF-I values between the GDM group and the non-GDM group were not different (P=0.834). Neonates with the heavier birth weight had the higher cord IGF-I levels. The most powerful predictor affecting cord IGF-I was birth weight and the next was maternal parity. Conclusion: Both cord blood adiponectin and IGF-I were associated with fetal growth, but IGF-I was a more general and direct factor affecting fetal body size, and adiponectin seemed to have more association with insulin sensitivity than growth.

Expression Profiles of the Insulin-like Growth Factor System Components in Liver Tissue during Embryonic and Postnatal Growth of Erhualian and Yorkshire Reciprocal Cross F1 Pigs

  • Pan, Zengxiang;Zhang, Junlei;Zhang, Jinbi;Zhou, Bo;Chen, Jie;Jiang, Zhihua;Liu, Honglin
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.7
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    • pp.903-912
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    • 2012
  • In Erhualian and Yorkshire reciprocal cross $F_1$ pig populations, we examined the mRNA expression characteristic of liver-derived IGF-1, IGF-1R, IGF-2, IGF-2R and IGFBP-3 during the embryonic and postnatal developmental periods (E50, E70, E90, D1, D20, D70, D120 and D180). Our results demonstrated that the IGF-system genes mRNA levels exhibited an ontogenetic expression pattern, which was potentially associated with the porcine embryonic development, postnatal growth, organogenesis and even the initiation and acceleration of puberty. The expression pattern of IGF-system genes showed variation in the reciprocal cross ($F_1$ YE and EY pigs). This study also involved the expression features of imprinted genes IGF-2 and IGF-2R. The parent-of-origin effect of imprinted genes was reflected by their differential expression between the reciprocal crosses populations. The correlation analysis also indicated that the regulatory network and mechanisms involved in the IGF system were a complex issue that needs to be more fully explored. A better understanding of IGF system components and their interactive mechanisms will enable researchers to gain insights not only into animal organogenesis but also into somatic growth development and even reproduction.

ENDOCRINE CHANGES AND CIRCULATING INSULIN-LIKE GROWTH FACTORS IN NEWBORN CALVES FED COLOSTRUM, MILK OR MILK REPLACER

  • Lee, C.-Y.;Head, H.H.;Feinstein, C.R.;Hayen, J.;Simmen, F.A.
    • Asian-Australasian Journal of Animal Sciences
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    • v.8 no.1
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    • pp.51-58
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    • 1995
  • To examine whether colostral growth factors are transferred to the general circulation, concentrations of plasma cortisol, insulin, prolactin, growth hormone, insulin-like growth factors(IGFs) -I and -II, IGF-binding proteins(IGFBPs) and total protein were measured in newborn calves fed colostrums, milk of milk replacer before and after feeding at 12 h intervals during the first two days after birth. Plasma protein concentrations increased with time after than in milk- or milk replacer-fed calves. The mean protein concentration was greater in colostrum-fed than in milk- or milk replacer-fed calves. Plasma cortisol levels transiently declined after each feeding regardless of the type of diet, while insulin levels tended to increase. Mean concentrations of these hormones did not differ between dietary groups, nor did they change with time after birth. Plasma concentrations of prolactin and growth hormone did not differ between dietary groups and also did not change with time after birth or after feeding. Concentrations of IGF-I and IGF-II transiently increased at the second feeding period, but these, as well as plasma IGFBP profiles, were not different between groups or before and after feeding. Results did not indicate significant transfer of colostral growth factors across the newborn ruminant small intestine.

Insulin-like Growth Factor-I Induces FABPpm Expression in C2C12 Myotubes (C2C12 myotube에서 insulin-like growth factor-I 이 FABPpm과 FAT/CD36 발현에 미치는 영향)

  • Kim, Hye Jin;Yoon, Hae Min;Lee, Won Jun
    • Journal of Life Science
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    • v.25 no.10
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    • pp.1098-1102
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    • 2015
  • FABPpm (plasma membrane-bound fatty acid binding protein ) is highly expressed in skeletal muscle. The principal role of this protein is modulating fatty acid uptake and metabolism. The influence of insulin-like growth factor-I (IGF-I), which is a major regulator of skeletal muscle cells, on FABPpm in skeletal muscle cells has not been investigated. To determine the effect of IGF-I on the expression of FABPpm, differentiated C2C12 murine skeletal muscle cells were treated with 20 ng/ml of IGF-I for different times. IGF-I increased the expression of FABPpm in a time-dependent manner. The mRNA level of FABPpm was measured by real-time quantitative PCR to determine whether the IGF-1-induced induction of FABPpm was regulated pretranslationally. The IGF-I treatment resulted in very rapid induction of the FABPpm mRNA transcript in the C2C12 myotubes. After 24 and 48 hr of the IGF-I treatment, FABPpm mRNA increased 130 and 179%, respectively. The increase in the protein expression returned to control levels after 72 hr of the IGF-I treatment, suggesting that IGF-1 regulated the FABPpm gene pretranslationally in skeletal muscle cells. This is the first evidence that IGF-I has a modulatory effect on the expression of FABPpm. In conclusion, IGF-I induced rapid transcriptional modification of the FABPpm gene in C2C12 skeletal muscle cells and exerted modulatory effects on FABPpm.