• Journal of Life Science
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• v.22 no.12
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• pp.1651-1657
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• 2012

Plectin and microtubule actin cross-linking factor 1 (MACF1) are architectural proteins that contribute to the function of skeletal muscle as generators of mechanical force. However, the influence of insulin- like growth factor-I (IGF-I), a master regulator of skeletal muscle cells, on plectin and MACF1 in skeletal muscle cells has not been demonstrated. The effect of IGF-I on plectin and MACF1 gene expression was investigated by treating differentiated C2C12 murine skeletal muscle cells with 20 ng/ml of IGF-I at different time points. The IGF-I treatment increased plectin protein expression in a dose-dependent manner. The mRNA level of plectin was measured by real-time quantitative PCR to determine if plectin induction was regulated pretranslationally. IGF-I treatment resulted in a very rapid induction of plectin mRNA transcript in C2C12 myotubes. Plectin mRNA increased by 140 and 180% after 24 and 48 hours of IGF-I treatment, respectively, and returned to the control level after 72 hours of IGF-I treatment. MACF1 mRNA increased 86 and 90% after 24 and 48 hours of IGF-I treat-ment, respectively, and returned to the control level after 72 hours of IGF-I treatment. These results suggested that the plectin gene is regulated pretranslationally by IGF-I in skeletal muscle cells. In conclusion, IGF-I induces a rapid transcriptional modification of the plectin and MACF1 genes in C2C12 skeletal muscle cells and has modulating effects on a cytolinker protein as well as on contractile proteins.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.618-628
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• 1999

Background: Cell growth is a balance between cell proliferation and cell death. Insulin-like growth factor-I(IGF-I), which binds IGF-I receptor(IGF-IR), mediates cellular proliferation as a potent mitogen. IGF binding protein-3(IGFBP-3) as a circulating major IGFBP can inhibit or enhance the effects of IGF-I on cellular growth by binding IGFs. Methods: We investigated the expressions of mRNA of IGF-I and IGF-IR by northern blot and phosphorylation of IGF-IR with the treatment of IGF-I by western blot in 3T3 fibroblast cells. The cellular proliferations of 3T3 cells with the treatments of IGF-I were evaluated using $^3H$-thymidine incorporation and MTT assay. Also to observe the effect of IGFBP-3 on cellular proliferation, 3T3 cells were treated with anti-IGFBP-3 and ${\alpha}IR_3$(monoclonal antibody to IGF-IR) alone or in combination. Results: Our results demonstrated that 3T3 cells showed mRNA expressions of IGF-I and IGF-IR and the IGF-I increased phosphorylation of IGF-IR. The treatments of 3T3 cells with IGF-I increased cellular proliferation in 5 % and 1 % seruma-containing media, not in serum-free media. The addition of anti-IGFBP-3 to neutralize IGFBP-3 showed 2-fold increase of cellular proliferation, and also co-incubation of anti-IGFBP-3 and ${\alpha}IR_3$ together showed similar increase of cellular proliferation in 3T3 cells. Interestingly, when the cells were pretreated with ${\alpha}IR_3$ for 4 hr, prior to the simultaneous addition of ${\alpha}IR_3$ and anti-IGFBP-3, anti-IGFBP-3-mediated cellular proliferation was decreased to control level. All of these results suggest that free IGF-I released from IGF-I/IGFBP-3 complex would be involved in the cellular proliferation. Conclusion: IGF-I is a mitogen through the activation of IGF-IR in 3T3 cells, and IGFBP-3 could be a potent inhibitor for IGF-I action by binding IGF-I.

• Korean Journal of Animal Reproduction
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• v.23 no.4
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• pp.323-331
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• 1999

The effects of insulin-like growth factor-I (IGF-I) and cumulus cells during in vitro maturation in porcine oocytes were examined. When follicular oocytes were cultured in medium with different concentrations of IGF-I, maturation rates were 60, 61 and 62 and 72% for 0, 15 and l0ng/$m\ell$ IGF-I. In medium with 10ng/$m\ell$ IGF-I, maturation rates were not significantly difference between oocytes with (68%) and without (52%) cumulus cells during the culture. In medium with-out IGF-I, however, the maturation rates in oocytes with cumulus cells (63%) was significantly (P＜0.05) higher than oocytes without cumulus cells (32%). On the other hand, when IGF-I was added for first 24 h period or later 24 h period of culture, maturation rates were higher in oocytes with (61 and 49%) that than without (49 and 45%) cumulus cells. In experiment used medium without fetal calf serum (FCS) and porcine follicular fluid (PFF), the maturation rates in oocytes with cumulus cells for 48 h (48 and 67%) or first 24 h (46 and 63%) period after culture were significantly (P＜0.01) higher than in oocytes without cumulus cells (16 and 18%) in the presence or absence of IGF-I. These results indicated that cumulus cells is essential on maturation in vitro in porcine oocytes, but IGF-I can promote oocytes maturation of oocytes without cumulus cells in medium with FCS and PFF.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.5
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• pp.733-741
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• 2007

The effects of intra-duodenal infusion of methionine (Met), lysine (Lys) and leucine (Leu) on dry matter intake (DMI), the concentrations of insulin-like growth factor I (IGF-I), growth hormone (GH) and insulin in plasma, and liver IGF-I mRNA level were investigated in two experiments for Liuyang Black growing wether goats. In Experiment 1, three goats ($10.0{\pm}0.1$ kg) were fitted with ruminal, proximal duodenal and terminal ileal fistulaes to determine the infusion amounts of Met, Lys and Leu at the duodenum according to essential amino acid flows into the duodenum and their apparent digestibility. The infusion amounts were 0.77 g/d, 0.91 g/d and 0.58 g/d respectively. In Experiment 2, 4 groups of goats (($10.0{\pm}0.2$ kg) for each group, were cannulated at the duodenum, and were infused with a mixture of Met, Lys and Leu (Control), or mixtures with 21% Met, Lys or Leu replaced with glutamate respectively on a nitrogenous basis. The replacement of 21% Met, Lys or Leu with glutamate did not affect intakes of maize stover, concentrate or both (p>0.05) when compared with the control. The replacement of 21% Met or Lys significantly (p<0.05) reduced plasma GH, insulin and IGF-I concentrations and liver IGF-I mRNA level. The replacement of 21% Leu with glutamate reduced (p<0.05) plasma IGF-I concentration only, but not plasma insulin and GH, as well as liver IGF-I mRNA level (p>0.05). The close relationships between supplying Met and Lys in the lumen of the duodenum and plasma IGF-I, GH and insulin concentrations, as well as liver IGF-I mRNA level in this study indicate that the effects of the limiting amino acids on nutrition of animals are likely intermediated via their effects on these hormones, and these hormone profiles could be used as intermediate markers for the limiting order of amino acids.

• Clinical and Experimental Pediatrics
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• v.51 no.12
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• pp.1329-1335
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• 2008

Purpose : This study aimed to determine the best cutoff line for insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 to discriminate between growth hormone deficiency (GHD) patients and the control group. Methods : Two hundred thirty subjects with normal controls (129 boys and 101 girls, aged 7-15 years), 14 patients with complete GHD (12 boys and 2 girls), and 17 patients with partial GHD (9 boys and 8 girls) were studied. IGF-I serum concentrations were measured by radioimmunoassay (RI), and IGFBP-3 concentrations were measured by immunoradiometric assay (IRMA). Results : The receiver operating characteristic (ROC) plot analysis showed that the best IGF-I and IGFBP-3 cutoff line was at -1 standard deviation (SD). By comparing IGF-I serum levels of GHD children within 1 SD of normal control, we determined the sensitivity (S) (87.5-100%) and specificity (Sp) (80-84.6%) according to the age group. For IGFBP-3, we determined the following values: S (58.7-85.7%) and Sp (79.2-85.5%). Eleven of 14 patients with complete GHD (78.5%) and 16 of 17 patients with partial GHD (94.1%) had IGF-I concentrations equal to or below -1 SD of the control group mean. Ten of 12 complete GHD children (83.3%) and 13 of 17 partial GHD children (76.5%) had IGFBP-3 concentrations equal or below -1 SD of the control group mean. Conclusion : We conclude that the measurement of IGF-I and IGFBP-3 concentrations might provide essential supplementary data in the diagnostic evaluation of patients with GHD. Our results support the need to use cutoff lines based on below -1 SD of the control.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.3
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• pp.437-443
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• 2003

Epidemiological data suggest that lycopene has anticancer activities in humans. Insulin-like growth factor-I receptor (IGF-IR) is a transmembrane tyrosine kinase that mediates the biological actions of IGFs and may play an active role in cancer progression. Because our previous in vitro studies have indicated lycopene inhibits HT-29 cell growth, the aim of this study was to determine whether lycopene induces apoptotic cell death and the inhibitory effect of lycopene on HT-29 cell growth is related to changes in IGF-IR levels and the receptor's intracellular signalling pathways. HT-29 cells were incubated for 4 days in serum-free medium in the presence of 0, 25, 50, or 100 $\mu$M lycopene, and the DNA fragmentation assay was performed. Cells treated with lycopene produced a distinct oligonucleosomal ladder with different sizes of DNA fragments, a typical characteristic of cells undergoing apoptosis. HT-29 cells were cultured for 4 days in serum-free medium in the presence of 0~100 $\mu$M lycopene and IGF-I (10nM) was added for 0~60 minutes immediately prior to lysate preparations. Western blot analysis of total lysates revealed that lycopene decreased the levels of IRS-1, Akt, phosphatidylinositol 3-kinase (PI3K), and IGF-IR $\beta$-subunit, and increased the levels of the IGF-IR precursor dose dependently. Lycopene also decreased IGF-I-induced phosphorylation of IGF-IR$\beta$, IRS-1 and Akt, which were, at least in part, due to decreased expression of these proteins. These results suggest that lycopene induces apoptosis of HT-29 cells by inhibiting IGF-IR signaling thereby interfering with an IGF-II-driven autocrine growth loop, which is known to exist in this cell line.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.549-556
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• 2001

Background : IGF-I is an important mitogen in many types of malignancies. Tumors also express many IGF binding proteins, which modulate IGF action. The propose of this study was to evaluate the effect of IGF-I and IGFBP on cell proliferation in mouse lung cancer cells (3LL). Methods : The cellular proliferation of 3LL with the treatment of growth factors was evaluated using MTT assay. Western ligand blot was performed in order to determine whether 3LL cells secrete IGFBPs and we evaluated the effect of IGFBP on cellular proliferation. Results : The treatment of 3LL cells with IGF-I increased cellular proliferation in a serum free media. Western ligand blot of conditioned medium of 3LL with $^{125}I$-IGF-I demonstrated one single major band with an estimated molecular mass of 24 kDa. This band was identified as IGFBP-4 with immunoblot analysis using antisera. The addition of anti-IGFBP-4 antibody to abrogate the effect of IGFBP-4 resulted in increased cellular proliferation suggesting that IGFBP-4 inhibits cell growth. Conclusion : IGF-I increases cellular proliferation, however the secreted IGFBP-4 has an inhibitory function on cell growth in 3LL. These findings suggest that IGF-I and IGFBP are involved in the cell proliferation.

• 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.

• Archives of Pharmacal Research
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• v.27 no.3
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• pp.324-333
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• 2004

To determine whether Insulin-like growth factor (IGF-I) treatment represents a potential means of enhancing the survival of cardiac muscle cells from adriamycin (ADR)-induced cell death, the present study examined the ability of IGF-I to prevent cell death. The study was performed utilising the embryonic, rat, cardiac muscle cell line, H9C2. Incubating cardiac muscle cells in the presence of adriamycin increased cell death, as determined by MTT assay and annexin V-positive cell number. The addition of 100 ng/mL IGF-I, in the presence of adriamycin, decreased apoptosis. The effect of IGF-I on phosphorylation of PI, a substrate of phosphatidylinositol 3-kinase (PI 3-kinase) or protein kinase B (AKT), was also examined in H9C2 cardiac muscle cells. IGF-I increased the phosphorylation of ERK 1 and 2 and $PKC{\;}{\zeta}{\;}kinase$. The use of inhibitors of PI 3-kinase (LY 294002), in the cell death assay, demonstrated partial abrogation of the protective effect of IGF-I. The MEK1 inhibitor-PD098059 and the PKC inhibitor-chelerythrine exhibited no effect on IGF-1-induced cell protection. In the regulatory subunit of PI3K-p85- dominant, negative plasmid-transfected cells, the IGF-1-induced protective effect was reversed. This data demonstrates that IGF-I protects cardiac muscle cells from ADR-induced cell death. Although IGF-I activates several signaling pathways that contribute to its protective effect in other cell types, only activation of PI 3-kinase contributes to this effect in H9C2 cardiac muscle cells.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.4
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• pp.532-537
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• 2005

Increasing of body weight has been one of the important economic factors in the poultry industry. Insulin-like growth factor (IGF)-I is a polypeptide that serves to regulate muscle development and body growth. Moreover, IGF-I is related to feed efficiency. However, there are few studies regarding the regulatory roles of chicken IGF-I/-II compared with that of mammals. Especially, the Korean Native Ogol Chicken (KNOC) has a lean body growth and its body weight is generally lighter than the broiler chicken. Therefore, this study was conducted to investigate associations among serum IGF-I/-II concentration, feed efficiency, and body growth in KNOC. The body weight and feed intake of KNOC were recorded from 20 to 36 weeks at 2 weeks intervals, and blood was taken every 2 weeks. Serum IGF-I/-II were measured by RIA. Chickens were divided into two groups, high and low serum IGF-I concentration. Generally, feed efficiency and growth performance (body weight and weight gain) in the high serum IGF-I group were higher than those of the low group during the experimental period. In particular, the body weight of the IGF-I high group were significantly different from those of the IGF-I low group at 34 and 36 weeks, respectively (p<0.05). Moreover, body weight, weight gain, and feed efficiency had a significant correlation with serum IGF-I at several weeks (p<0.05 and p<0.01). These results show that IGF-I plays an important role in body growth and suggests a possibility that serum IGF-I could be used as a selection marker for body growth in KNOC.