• Molecules and Cells
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• v.28 no.3
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• pp.189-194
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• 2009

The modulating effect of IGF-I on the regulation of AR gene expression and activation in skeletal muscle cells remains poorly understood. In this study, the effects of IGF-I treatment on AR induction and activation in the absence of AR ligands were examined. Differentiating C2C12 cells were treated with different concentrations (0-250 ng/ml) of IGF-I or for various periods of time (0-60 min) of 250 ng/ml IGF-I. Treatment of C2C12 cells with IGF-I resulted in a dose- and time-dependent increase in total AR and phosphorylated AR (Ser 213). IGF-I treatment also led to significantly increased AR mRNA expression when compared with the control. The levels of skeletal ${\alpha}-actin$ and myogenin mRNA, known target genes of AR, were also significantly upregulated after 5 or 10 min of treatment with IGF-I. Confocal images revealed that IGF-I stimulated nuclear localization of AR in the absence of ligands. In addition, an electrophoretic mobility shift assay indicated that IGF-I stimulated the AR DNA binding activity in a time-dependent manner. The present results suggest that IGF-I stimulates the expression and activation of AR by ligand-independent mechanism in differentiating C2C12 mouse skeletal muscle cells.

• 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.

• BMB Reports
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• v.48 no.6
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• pp.342-347
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• 2015

The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC) cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFRexpressing MDA-MB-436 cells show high sensitivity to insulinstimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells. [BMB Reports 2015; 48(6): 342-347]

• Advances in pediatric surgery
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• v.3 no.2
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• pp.98-107
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• 1997

To determine whether bile juice exclusion can prevent the mucosal damage, and Insulin-like growth factor-I can promote mucosal regeneration in ischemia-reperfusion injury of the bowel, 39 weanling rats with 10 cm of Thiry-Vella loop were studied. Animal groups were; Control, BL(common bile duct ligation), IGF{insulin-like growth factor-I(IGF-I) infusion} and IGF-BL(combined treatment). IGF-I(1.5 mg/kg/day) was continuously delivered through a subcutaneously implanted miniosmotic pump. After 15 minutes of superior mesenteric artery clamping, a tissue specimen(P) was taken after 30 minutes of reperfusion. Intestinal continuity was restored to allow oral feeding. A specimen of main tract(M) and another of the Thiry-Vella loop(T) were collected for histomorphometry after 48 hours of reperfusion and free feeding. Villus size ratio(VSR), crypt depth(CD), crypt-depth/villus-height ratio(CVR) and injury score(IS) were measured in 15 consecutive villi. The postoperative mortalities of bile duct ligation groups(BL and IGF-BL) were higher than those of other groups. In control group, VSR of M was lower(P<0.05) than P or T, but not in the other groups. VSR of M in control was lower than those in other groups. CD of T in control, IGF and IGF-BL group were higher than those of M. CD of M and T showed gradual increments from control, IGF and IGF-BL group, respectively. CVR of M and T in IGF group were higher than those in control. CVR in IGF-BL group, T was higher than M, and M was higher than P. About IS, M of BL($20.1{\pm}2.5$) and IGF-BL($20.9{\pm}3.3$) groups were significantly lower than that of control($32.4{\pm}2.5$). These results suggest that the exclusion of bile juice reduces the severity of the reperfusion injury of the mucosa, by inability to activate pancreatic enzymes and IGF-I stimulates mucosal regeneration in injured bowel, and the effect is potentiated by bile juice exclusion.

• Journal of Genetic Medicine
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• v.2 no.1
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• pp.41-47
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• 1998

Human uniparental gestations such as gynogenetic ovarian teratomas provide a model to evaluate the integrity of parent-specific gene expression - i.e. imprinting - in the absence of a complementary parental genetic contribution. The few imprinted genes characterized so far include the insulin-like growth factor-2 gene (IGF2) coding for a fetal growth factor and H19 gene whose normal function is unknown but it is likely to act as an mRNA. IGF2 is expressed by the paternal allele and H19 by the maternal allele. This reciprocal expression is quite interesting because both H19 and IGF2 genes are located close to each other on chromosome 11p15.5. In situ RNA hybridization analysis has shown variable expression of the H19 and IGF2 alleles according to the tissue origin in 11 teratomas. Especially, Skin, derivative of ectoderm, is expressed conspicuously. We examined imprinting of H19 and IGF2 in teratomas using PCR and RT-PCR of exonic polymorphism. H19 and IGF2 transcript could be expressed either biallelically or monoallelically in the teratomas. Biallelic expression (i.e., loss of imprinting) of IGF2 occurred in 5 out of 6 mature teratomas and 1 out of 1 immature teratoma. Biallelic expression of H19 occurred in 4 out of 10 mature teratomas and 1 out of 1 immature teratoma. Expression levels of H19 and IGF2 transcript using the semi-quantitative RT-PCR had no relation between monoallelic and biallelic expression. Moreover, IGF2 biallelic expression did not affect allele-specificity or levels of H19 expression. These results demonstrate that both genes, H19 and IGF2, can be imprinted, expressed and regulated independently and individually of each other in ovarian teratoma.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8633-8636
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• 2016

Background: To investigate the expression of insulin-like growth factor-I receptor (IGF-IR) and sushi domain containing protein 3 (SUSD3) in breast cancer tissue, and analyze their relationship with clinical parameters and the correlation between the two proteins. Materials and Methods: The expression of IGF-IR and SUSD3 in 100 cases of breast cancer tissues and adjacent normal breast tissues after surgery was detected by immunohistochemical technique MaxVisionTM, and the relationship with clinical pathological features was further analyzed. Results: The positive rate of IGF-IR protein was 86.0% in breast cancer, higher than 3.0% in adjacent normal breast tissue (P<0.05). The positive expression rate of SUSD3 protein was 78.0% in breast cancer, higher than 2.0% in adjacent normal breast tissue (P<0.05). The expression of IGF-IR and SUSD3 was related to estrogen receptor and pathological types (P<0.05),but not with age, stage, the expression of HER-2 and Ki-67 (P>0. 05). The expression of IGF-IR and SUSD3 in breast cancer tissue was positively related (r=0.553, P<0.01). Conclusions: The expression of IGF-IR and SUSD3 may be correlated to the occurrence and development of breast cancer. The combined detection of IGF-IR, SUSD3 and ER may play an important role in judging prognosis and guiding adjuvant therapy after surgery of breast cancer.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.10
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• pp.1451-1457
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• 2016

A comparative study was performed to investigate the efficacy of KiFAY as a feed additive on performance parameters, thyroid, and pancreatic hormone levels in broilers. Ninety birds (Vencobb 400) were randomly divided into three groups viz., Control (no DL-methionine supplementation), Treatment1 (containing added DL-methionine) and Treatment 2 (containing KiFAY and without DL-methionine supplementation). The performance parameters (weekly body weight, body weight gain, feed intake, and feed consumption ratio) were recorded and calculated during the whole study of 4 weeks. Analyses of insulin and insulin-like growth factor (IGF 1), triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) were performed at the end of the study. The results show that birds on supplementation of KiFAY performed significantly (p<0.001) better than other treatments. The weekly body weight, body weight gain, feed in-take and feed consumption ratio improved in KiFAY treated birds. The study found an increase in insulin and IGF1 levels (p<0.001) in KiFAY compared with the other treatments. Serum T3, T4, and TSH levels in the Treatment 2 were higher than other treatments (p<0.001). The KiFAY supplementation was able to improve performance with associated responses at a hormonal level in broilers.

• 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.

• 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.

• KSBB Journal
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• v.17 no.4
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• pp.403-408
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• 2002

For stimulating the in vivo secretion of IGF-1 (insulin-like growth factor-1) which is well known to promote the various physiological actions in human body, the natural herbal extract, YGF251 (young growth factor 251), was developed and evaluated for its effect as IGF-1 secretagogue in this study. The clinical study was peformed as double blind test, and 31 adult female and male volunteers between the age of 40 and 70 were investigated for their changes of concentration of IGF-1 , insulin level, weight, blood pressure, and liver and kidney functions. As the result of paired sample test on the change of the concentration of IGF-1, in YGF251 treated group, it was 245.6 ng/mL before dosing. The concentration of IGF-1 was increased to 269.3 ng/mL after a month and to 275.6 ng/mL after two months, and both were statistically significant (p〈0.05). While in control group, the concentration of IGF-1 was 280.0 ng/mL before dosing, but decreased to 239.2 ng/mL after a month and to 230.2 ng/mL after two months, and both were also statistically significant (p〈0.05). In YGF251 treated group, the concentration of insulin in blood increased about 2 times after a month dosing as an average level, but in control group, it showed a decrease of 36% compared with before dosing. And there were little changes regarding to the measured weight and blood pressure. Various measured data in order to observe the alteration in liver and kidney functions by the administration of YGF251 showed a little change within measuring error range.