• Title/Summary/Keyword: Insulin-like growth factor-1 receptor

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The Regulation of Insulin-Like Growth (IGF) Factors and IGF Binding Proteins by High Glucose in Mesangial Cells

  • Park Soo-hyun
    • Biomedical Science Letters
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    • v.10 no.3
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    • pp.203-210
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    • 2004
  • It has been reported that glomerulosclerosis mediated by the dysfunction of mesangial cells and insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known the effect of high glucose on IGF-I, -II secretion, IGF-I receptor, and IGFBPs expression in the mesangial cells. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and oxidative stress in mesangial cells. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion and mRNA expression (P<0.05), which was blocked by PKC inhibitor (staurosporine, 10/sup -8/ M) and antioxidant (N-acetyl cystein, 10/sup -5/ M). High glucose decreased IGFBP-1 and -2 expression but increased IGFBP-5 expression. These alteration of IGFBPs by high glucose was also prevented by staurosporine and NAC, suggesting the role of PKC and oxidative stress. Indeed, high glucose increased PKC activity. Furthermore, high glucose-induced increase of lipid peroxide (LPO) formation was blocked by PKC inhibitors. In conclusion, high glucose alters IGF system via PKC-oxidative pathways in mesangial cells.

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Effect of Dietary Conjugated Linoleic Acid (CLA) on Abdominal Fat Deposition in Yellow-feather Broiler Chickens and Its Possible Mechanism

  • Zhou, J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.12
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    • pp.1760-1765
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    • 2008
  • A total of 60 one-day-old Yellow-feather broiler chickens were allotted into treatment and control groups. The treatment group was fed with the diet supplemented with 3% conjugated linoleic acid (CLA) for 48 d, while control group was fed with the diet supplemented with 3% rapeseed oil. Chickens were slaughtered in each group at the age of 49 d, and the blood and the abdominal adipose tissue were sampled. Serum cLeptin and serum cAdiponectin were measured by ELISA. The total RNA was extracted from adipose tissue to measure the abundance of the chicken growth hormone receptor (cGHR), insulin-like growth factor 1 (cIGF-1), insulin-like growth factor I receptor (cIGF-IR), peroxisome proliferator-activated receptor gamma ($cPPAR{\gamma}$), cAdiponectin and cAdipoIR mRNA by RT-PCR using ${\beta}$-actin as an internal standard. Results showed that the CLA decreased the abdominal fat index by 20.93% (p<0.05). The level of serum cLeptin but not serum cAdiponectin was significantly increased by CLA treatment (p<0.05). CLA down-regulated the relative abundance of cGH-R mRNA and $cPPAR{\gamma}$ mRNA in abdominal adipose tissue by 24.74% (p<0.05) and 66.52% (p<0.01) respectively. However, no differences were found between CLA treatment group and control group (p>0.05) in the relative abundance of cIGF-1, cIGF-IR, cAdiponectin, and cAdipoIR mRNA in abdominal adipose tissue. The data suggested that CLA inhibited abdominal fat deposition in broiler chicken may be determined by decreasing the GHR available for GH, and by inhibiting the differentiation of preadipocytes via down-regulation of $PPAR{\gamma}$, but independent of IGF and (or) GH-IGF pathway or adiponectin action.

Association of Insulin Receptor Substrate-1 G972R Variant with Non-small Cell Lung Cancer Risk

  • Lee, Chang Youl;Ahn, Chul Min;Jeon, Jeong Hee;Kim, Hyung Jung;Kim, Se Kyu;Chang, Joon;Kim, Sung Kyu;Chang, Yoon Soo
    • Tuberculosis and Respiratory Diseases
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    • v.67 no.1
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    • pp.8-13
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    • 2009
  • Background: The insulin receptor substrate-1 (IRS-1) is the primary docking molecule for the insulin-like growth factor I receptor (IGF-IR), and is required for activation of the phosphatidylinositol 3'-kinase (PI3K) pathway. IRS-1 activation of the (PI3K) pathway regulates IGF-mediated survival, enhancement of cellular motility and apoptosis. Therefore, we attempted to ascertain whether IRS-1 genetic variations affect an individual's risk for non-small cell lung cancer (NSCLC). Methods: Two-hundred and eighteen subjects, either diagnosed with NSCLC or control subjects, were matched by age, gender and smoking status. Genomic DNA from each subject was amplified by PCR and analyzed according to the restriction fragment length polymorphism (RFLP) profile to detect the IRS-1 G972R polymorphism. Results: The frequencies of each polymorphic variation, in the control population, were as follows: GG=103 (94.5%) and GR=6 (5.5%); for the NSCLC subjects, the genotypic frequencies were as follows: GG=106 (97.2%) and GR=3 (2.8%). We could not demonstrate statistically significant differences in the genotypic distribution between the NSCLC and the control subjects (p=0.499, Fisher's Exact test). The relative risk of NSCLC, associated with the IRS-1 G972R polymorphic variation, was 1.028 (95% CI; 0.63~9.90). In addition, we found no differences between polymorphic variants with regard to the histological subtype of NSCLC. Conclusion: We did not observe any noteworthy differences in the frequency of the IRS-1 G972R polymorphism in NSCLC patients, compared to control subjects. These results suggest suggesting that, in our study population, the IRS-1 G972R polymorphism does may not appear to be associated with an increased risk of NSCLC.

MITOGENIC EFFECTS OF NICOTINE TO HUMAN PERIODONTAL LIGAMENT(PDL) CELLS IN VITRO (In Vitro에서 니코틴이 치주인대세포에 미치는 세포분열효과에 대한 연구)

  • Row, Joon;Chun, Youn-Sic
    • The korean journal of orthodontics
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    • v.27 no.6 s.65
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    • pp.955-961
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    • 1997
  • Nicotine is one of the major components of cigarette smoking which causes various systemic and local diseases to human body. Mitogenic effects of nicotine to systemic disease are interesting factors in the results of cellular Proliferation especially to vascular and pulmonary tissue or cells. The study of local effects concerns with destruction of tissue and delayed healing rate after various surgical treatment. Platelet-Derived Growth factor(PDGF) and Insulin-like growth factor(IGF) are blown as major mitogens to human PDL cells. The purpose of this study was to investgate the mitogenic effects of nicotine to human PDL cells. We studied the expression of PDGF-$\alpha$ receptor, PDGF-$\beta$receptor, and IGF-l receptor mRNA from the nicotine treated human PDL cells by northern analysis. The experimental groups were divided into different serum($1\%,\;10\%$) and nicotine (100ng/m1,1000ng/m1) concentrations and each group was studied by time course. The results of this study showed upregulation of PDGF-${\alpha},\;{\beta}$ receptor and IGF-l receptor mRNA at 100ng/ml nicotine concentration and $10\%$ serum group to the time course. These results suggest that physiologically attainable nicotine concentrations may stimulate the mitogenic gene synthesis to human PDL cells in vitro.

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Effects of the Insulin-like Growth Factor Pathway on the Regulation of Mammary Gland Development

  • Ha, Woo Tae;Jeong, Ha Yeon;Lee, Seung Yoon;Song, Hyuk
    • Development and Reproduction
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    • v.20 no.3
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    • pp.179-185
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    • 2016
  • The insulin-like growth factor (IGF) pathway is a key signal transduction pathway involved in cell proliferation, migration, and apoptosis. In dairy cows, IGF family proteins and binding receptors, including their intracellular binding partners, regulate mammary gland development. IGFs and IGF receptor interactions in mammary glands influence the early stages of mammogenesis, i.e., mammary ductal genesis until puberty. The IGF pathway includes three major components, IGFs (such as IGF-I, IGF-II, and insulin), their specific receptors, and their high-affinity binding partners (IGF binding proteins [IGFBPs]; i.e., IGFBP1-6), including specific proteases for each IGFBP. Additionally, IGFs and IGFBP interactions are critical for the bioactivities of various intracellular mechanisms, including cell proliferation, migration, and apoptosis. Notably, the interactions between IGFs and IGFBPs in the IGF pathway have been difficult to characterize during specific stages of bovine mammary gland development. In this review, we aim to describe the role of the interaction between IGFs and IGFBPs in overall mammary gland development in dairy cows.

Lack of any Prognostic Role of Insulin-Like Growth Factor-1 Receptor in Non-Small Cell Lung Cancer

  • Dilli, Utku Donem;Yildırim, Mustafa;Suren, Dinc;Alikanoglu, Arsenal;Kaya, Vildan;Goktas, Sevil;Yildiz, Mustafa;Sezer, Cem;Gunduz, Seyda
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5753-5757
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    • 2014
  • Background: The purpose of this study is to determine whether the IGF1R expression has a prognostic role in non-small cell lung cancer. Materials and Methods: Forty-seven patients histopathologically diagnosed with small cell lung cancer upon bronchoscopic biopsy or resection materials were included in the study. IGF1R expression was examined via immunohistochemical methods. In samples, >10% staining were assessed as positive and ${\leq}10%$ as negative. Information about demographic datas and treatments was obtained by retrospective searches of patient files. Results: IGF1R expression was determined as positive in 38 (80.9%) and as negative in 9 (19.1%) patients. There was no significant relation between IGF1R expression and histological sub-type, local invasion, lymph node and metastasis status (p=0.842, p=0.437, 0.064, 0.447, respectively). There was also no correlation with IGF1R expression and survival (p=0.141). Conclusions: There are conflicting results between IGF1R and its prognostic effects in the various studies. It has been claimed in some studies it is not related to prognosis as in our study, and in some studies it has been claimed that it is a good prognostic factor whereas in some studies it has been claimed as being a factor for worse prognosis. We think that IGF1R expression in non-small cell lung carcinoma patients deserves further analysis, because of its potential prognostic and predictive roles.

Linseed oil supplementation affects fatty acid desaturase 2, peroxisome proliferator activated receptor gamma, and insulin-like growth factor 1 gene expression in turkeys (Meleagris gallopavo)

  • Szalai, Klaudia;Tempfli, Karoly;Zsedely, Eszter;Lakatos, Erika;Gaspardy, Andras;Papp, Agnes Bali
    • Animal Bioscience
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    • v.34 no.4
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    • pp.662-669
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    • 2021
  • Objective: Effects of linseed oil (LO) supplementation on the fat content and fatty acid profile of breast meat, and the expression of three genes in the liver, breast muscle and fat tissues of commercial 154-day-old hybrid male turkeys were investigated. Methods: The animals in the control group were fed a commercially available feed and received no LO supplementation (n = 70), whereas animals in the LO group (n = 70) were fed the same basic diet supplemented with LO (day 15 to 21, 0.5%; day 22 to 112, 1%). The effect of dietary LO supplementation on fatty acid composition of breast muscle was examined by gas chromatography, and the expression of fatty acid desaturase 2 (FADS2), peroxisome proliferator activated receptor gamma (PPARγ), and insulin-like growth factor 1 (IGF1) genes was analysed by means of quantitative reverse transcription polymerase chain reaction. Results: The LO supplementation affected the fatty acid composition of breast muscle. Hepatic FADS2 levels were considerably lower (p<0.001), while adipose tissue expression was higher (p<0.05) in the control compared to the LO group. The PPARγ expression was lower (p<0.05), whereas IGF1 was higher (p<0.05) in the fat of control animals. There were no significant (p>0.05) differences in FADS2, PPARγ, and IGF1 gene expressions of breast muscle; however, omega-6/omega-3 ratio of breast muscle substantially decreased (p<0.001) in the LO group compared to control. Conclusion: Fatty acid composition of breast meat was positively influenced by LO supplementation without deterioration of fattening parameters. Remarkably, increased FADS2 expression in the liver of LO supplemented animals was associated with a significantly decreased omega-6/omega-3 ratio, providing a potentially healthier meat product for human consumption. Increased PPARγ expression in fat tissue of the LO group was not associated with fat content of muscle, whereas a decreased IGF1 expression in fat tissue was associated with a trend of decreasing fat content in muscle of the experimental LO group.

Expression Patterns of Growth Related Genes in Juvenile Red Spotted Grouper (Epinephelus akaara) with Different Growth Performance after Size Grading

  • Mun, Seong Hee;You, Jin Ho;Oh, Hyeon Ji;Lee, Chi Hoon;Baek, Hea Ja;Lee, Young-Don;Kwon, Joon Yeong
    • Development and Reproduction
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    • v.23 no.1
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    • pp.35-42
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    • 2019
  • Fish shows great difference in growth rate between individuals during larval development and early growth. This difference seriously reduces the production efficiency in fish culture. Growth hormone (GH)/Insulin-like growth factor 1 (IGF1) system is said to play some pivotal roles in fish growth. In this study, we investigated differences of GH, IGF1 and GHR gene expressions in juvenile red spotted grouper (Epinephelus akaara) with different growth performance. Red spotted groupers were reared under the same environmental condition (water temperature $24{\pm}1^{\circ}C$, natural light) for 96 days after hatching. They were divided into 3 groups by size (fast growing, middle growing and slow growing groups: FGG, MGG, and SGG, respectively). RNA was extracted from the brain, liver and muscle tissues from each group, and target gene expression was examined by real-time PCR. In the brain with pituitary gland, expression of GH gene in FGG was significantly higher than the expression in SGG, but the expression of IGF1 and GHR genes in the muscle was highest in SGG. Difference of GHR and IGF1 mRNA in the liver between groups with different growth performance was less clear than that in other tissues, although level of IGF1 mRNA was higher in SGG than in MGG. These results suggest that hormonal governing of growth is not the same in fast growing and slow growing fish, and size grading could cause a shift of hormonal state and growth pattern in this species.

Effects of Cheunggyeongsamul-tang Extract on Longitudinal Bone Growth in Adolescent Female Rats (청경사물탕(淸經四物湯) 추출물의 성장기 흰쥐 장골길이 성장에 대한 효과)

  • Lee, Jung-Hun;Lee, Se-Na;Son, Jae-Bong;Keum, So-Hyun;Leem, Kang-Hyun
    • The Korea Journal of Herbology
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    • v.24 no.4
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    • pp.149-157
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    • 2009
  • Objectives : This study was designed to investigate the effects of Cheunggyeongsamul-tang extract on the growth of longitudinal bone in adolescent female rats. Methods : Longitudinal bone growth was measured by fluorescent microscopy. To examine the effects on the growth plate metabolism, the total height of growth plate, the induction of local insulin-like growth factor-1 (IGF-1), IGF-1 receptor, bone morphogenetic protein-2 (BMP-2), BMPR-1A, indian hedgehog (IHH), and parathyroid hormone-related protein (PTH-rP) were measured. Results : Cheunggyeongsamul-tang extract enhanced longitudinal bone growth and total height of the growth plate. Also, it promoted the induction of local IGF-1, BMP-2, IHH and PTH-rP of the growth plate. Conclusions : This study shows that the Cheunggyeongsamul-tang extract effects longitudinal bone growth in adolescent rats and might be used for both stunted adolescents and inherent growth failure patients.

Distribution of Insulin-Like Growth Factor-Binding Proteins(IGFBPs) and IGFBP-3 Proteolysis in Noninsulin-Dependent Diabetes Mellitus Serum (인슐린 비의존형 당뇨병 환자의 혈청 중 Insulin-Like Growth Factor-Binding Proteins(IGFBPs)의 분포 및 IGFBP-3의 분해)

  • Lee, Hwa-Jin;Kim, Sung-Hyun;Kwon, Mi-Jin;Nam, Taek-Jeong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.2
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    • pp.285-290
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    • 1997
  • The insulin-like growth factors(IGFs) are bound to several binding proteins(IGFBPs) that appear to regulate IGF transport, receptor binding, and its action. The concentration of these peptides are altered by catabolic conditions. To determine IGF-I and IGFBP levels in noninsulin-dependent diabetes mellitus (NIDDM), sera was obtained from 5 patients and 7 controls. Serum levels of IGF-I in NIDDM were lower than those in either of the controls. By western immunoblot analysis, especially IGFBP-1 levels are increased, whereas IGFBP-3 levels decreased and their fragments was increased in NIDDM serum. IGFBP-3 proteolytic activity in NIDDM sera was inhibited by phenylmethylsulfonylfluoride (PMSF), aprotinin, and ethylenediaminetetraacetic acid(EDTA). This pattern of inhibition was consistent with a metal-dependent serine protease. By gelatin zymography, these proteolytic enzymes were identified as the size of 97 and 69 kDa. IGFBP-1, which is primarily insulin regulated, was increased in NIDDM and may modulate circulating IGF-I levels by regulating capillary passage of IGF-I. IGFBP-3 proteolysis markedly reduces its affinity for the IGFs, particularly for IGF-I. This accelerates their kinetics of dissociation, thereby increasing the proportions of IGF-I in free form and its availability to the cells.

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