• 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.

• Korean Journal of Animal Reproduction
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• v.27 no.1
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• pp.1-7
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• 2003

Transgenic rabbits were produced by DNA microinjection using growth hormone receptor (GHR) and IGF-1 receptor (IGF-1R) genes fused to metallothionein(MT) promoter. The overall efficiencies for production of transgenic rabbits were 3.2% and 3.1% for GHR and IGF-lR genes, respectively. Founder rabbits transmitted transgenes to their progenies through medelian fashion. Growth rate of GHR and IGF-lR transgenic rabbits was significantly faster than that of non-transgenic rabbits. Transgenic rabbits grew large. (25% and 15% increase in body weight of GHR and IGF-lR transgenic rabbits, respectively) than non-transgenic rabbits and organ weight of transgenic rabbits increased, suggesting that GHR and IGF-1R genes affects growth rates in transgenic rabbits.

• The korean journal of orthodontics
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• v.31 no.6 s.89
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• pp.589-600
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• 2001

Insulin-like growth factor I (IGF-I) has the local tissue regulating actions. In bone, IGF-I increases the replication of osteoblastic lineage, probably preosteoblasts, and enhances osteoblastic collagen synthesis and matrix composition rates. The purpose of this study was to investigate the local regulatory effect of IGF-I on periodontium totally, both in an autocrine and paracrine manner. To examine the effect of IGF-I directly on osteoblast (OB) of test rats, and indirectlv on OB via periodontal ligament fibroblast (PDLF), and the effect of gingival fibroblast (GF) on OB via cellular paracrine manner for the understanding of humoral action of adjacent tissue, GF and PDLF were obtained from male Sprague-Dawley rats of six to eight weeks of age. OB was obtained iron frontal and parietal calvarial bone of Sprague-Dawley 21day-old-fetus. After each tell was Incubated 24 hours, for collecting conditioned medium, different concentrations of IGF-I (1,10,100 ng/ml,1ml/well) was adding in the GF, PDLF cells, and the supernatant from these cultures was put into the primary OB culture with $1{\times}10^4$cell/ml/well. The experimental group was divided into six groups control OB, IGF-I treated OB, OB culture with conditioned medium from PDLF, OB culture with conditioned medium from IGF-I treated PDLF, OB culture with conditioned medium from GF, OB culture with conditioned medium from IGF-I treated GF. After final IGF-I treatment, OB was Incubated for 24 hours, and alkaline phosphatase activity assay, BMP expression, cell proliferation measurement using MTT assay, total protein measurement, Collagen synthesis assay using western blot, and examination of bone nodule synthesis were done. Alkaline phosphatase expressions were increased in the group of PDLF-IGF-I supernatant treatment. Direct IGF-I treatment with concentrations of 100ng/m1 showed increased viable tell number measured by MTT assay. And IGF-I treatment did not increase total protein amount. The entire experimental group showed BMP2, 4 expression in western blot, and there was no significant difference between control and experimental groups. These results suggested that supernatant from PDLF effects on increasing cellular activities of OB regardless of IGF-I, and at high concentration, IGF-I increases OB tell proliferation.

• 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.

• 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.

• Korean Journal of Veterinary Research
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• v.40 no.3
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• pp.489-496
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• 2000

This study was conducted to investigate the effects of streptozotocin-induced (STZ) diabetes on insulin-like growth factor-I (IGF-I), insulin-like growth factor binding proteins (IGFBPs), and IGF-I carrier proteins in serum, liver, and kidney. The levels of total and free IGF-I were measured by radioimmunoassay (RIA). The patterns of IGFBPs were determined by western ligand blotting (WLB) analysis. The profiles of IGF-I carrier proteins in serum were determined by column chromatography. The levels of total and free IGF-I in serum were lower in STZ-induced diabetic rat than normal rat (p<0.01). Similarly, the levels of total IGF-I in liver was lowered in STZ-induced diabetic rats. On the other hand, the levels of total IGF-I in kidney were increased in STZ-induced diabetic rats compared with normal rats (p<0.01). In serum and liver from STZ-induced diabetic rats, the amount of IGFBP-3 was decreased and the amount of IGFBP-2 was increased compared with normal rats. There was a not difference in amount of IGFBP-4 in serum between STZ-induced diabetic rats and normal rats. The serums of normal rats have higher 150kDa carrier proteins than in STZ-induced diabetic rats, whereas, most of 50kDa carrier proteins were found in STZ-induced diabetic rats. These results demonstrate that in STZ-induced diabetic rats, IGF-I/IGFBPs system that included functional bioactivity was changed in serum as well as tissues, and these changes may play an important role in pathogenesis of diabetes.

• Journal of Microbiology and Biotechnology
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• v.9 no.1
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• pp.113-118
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• 1999

The insulin-like growth factor (IGF) is found in all vertebrates and its type-II molecule is regarded as a fundamental embryonic growth factor during development. We have firstly identified, in this study, a cDNA clone corresponding to IGF-II (flIGF-II) from the adult brain of the teleost, Paralichthys olivaceus. We also examined the tissue expression of flIGF-II in several adult tissues by RT-PCR. The flIGF-II cDNA contained a complete ORF consisting of 215 amino acids and one stop codon. Its molecular characteristics appear to be similar to the previously identified IGF-II molecules, in which a common primary structure exhibiting B, C, A, D, and E domains is evidently observed. This cDNA clone seems to be cleaved at $Ala_{52}$ for the $NH_2$-end signal peptide and appears to produce a 98 amino acid-long E-peptide from the $Arg^{118}$. The functional B-D domain regions, therefore, include 65 amino acids and is able to encode a 7.4-kDa protein. The most prominent structural difference between IGF-I and IGF-II was that the D domain of IGF-II exhibits a two-codon-deleted pattern compared to the 8 amino acid-containing IGF-I. The insulin family signature in the A domain and six cysteins forming three disulfide bridges between the B and A domains were evolutionary-conserved from teleosts to mammalian IGF-II. Interestingly, the E-peptide region appears to provide a distinct hallmark between teleosts in amino acid composition. The flIGF-II shows 85.1% of sequence identity to salmon and trout, 90.6% to tilapia, and 98.4% to perch in amino acid level. In tissue expressions of IGF-II, it is very likely that flIGF-II has a significant expression in the adult brain. However, liver seems to be the main source for IGF-II production, and relatively low signals were observed in the adult muscle and kidney. Taken together, it would be concluded that the functional region for IGF-II mRNA is highly similar in phylogeny and is evolutionary, conserved as a mediator for the growth of vertebrates.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.31 no.5
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• pp.774-778
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• 1998

The effect of insulin-like growth factor-I (IGF-I) on circulating insulin-like growth factor binding proteins (IGFBPs) in the Korean rockfish, Sebastes schlegeli, was assessed after injected of recombinant human IGF-I (6 $\mu$g/100 g body weight). Growth and metabolic status of each fish were assessed by determing body length and body weight changes, and serum glucose concentration. Serum IGF binding proteins concentrations were assessed by the Western ligand blot procedure using $^{125}I$-labeled human IGF-I tracer. The fish received IGF-I were Heavier than the saline-injected control fish after 2 weeks of treatment. Plasma IGFBP-3 concentration inclosed, but plasma IGFBP-1 and glucose levels decreased significantly after administration. Taken together, the findings of this study suggest that human IGF-I is biologically active in Korean rockfish and may be of significance in metabolic and growth-related processes.

• Molecules and Cells
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• v.28 no.6
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• pp.589-593
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• 2009

In this study, the roles of the p38 MAPK, ERK1/2 and JNK signaling pathway in IGF-I-induced AR induction and activation were examined. C2C12 cells were treated with IGF-I in the absence or presence of various inhibitors of p38 MAPK (SB203580), ERK1/2 (PD98059), and JNK (SP600125). Inhibition of the MAPK pathway with SB203580, PD98059, or SP600125 significantly decreased IGF-I-induced AR phosphorylation and total AR protein expression. IGF-I-induced nuclear fraction of total AR and phosphorylated AR were significantly inhibited by SB203580, PD98059, or SP600125. Furthermore, IGF-I-induced AR mRNA and skeletal ${\alpha}-actin$ mRNA were blocked by those inhibitors in dose-dependent manner. Confocal images showed that IGF-I-induced AR nuclear translocation from cytosol was significantly blocked by SB203580, PD98059, or SP600125, suggesting that the MAPK pathway regulates IGF-I-induced AR nuclear localization in skeletal muscle cells. The present results suggest that the MAPK pathways are required for the ligand-independent activation of AR by IGF-I in C2C12 skeletal muscle cells.

• Molecules and Cells
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• v.28 no.5
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• pp.495-499
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• 2009

Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR and IGF-I in skeletal muscle cells has not been previously examined. In this study, the role of PI3K/Akt on IGF-I-induced gene expression and activation of AR in skeletal muscle cells was investigated. C2C12 cells were treated with IGF-I in the absence or presence of inhibitors of PI3K/Akt pathway (LY294002 and Wortmannin). Inhibition of the PI3K/Akt pathway with LY294002 or Wortmannin led to a significant decrease in IGF-I-induced AR phosphorylation and total AR protein expression. Furthermore, IGF-I-induced AR mRNA and skeletal ${\alpha}-actin$ mRNA were blocked by LY294002 or Wortmannin. Confocal images showed that IGF-I-induced AR translocation from cytosol to nucleus was inhibited significantly in response to treatment with LY294002 or Wortmannin. The present results suggest that modulating effect of IGF-I on AR gene expression and activation in C2C12 mouse skeletal muscle cells is mediated at least in part by the PI3K/Akt pathway.