• Korean Journal of Veterinary Research
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• v.39 no.5
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• pp.938-944
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• 1999

The insulin-like growth factor-I(IGF-I) is an important metabolic factor involved in cell growth and metabolism. Although secretion of IGF-I in rat liver is regulated by growth hormone, the effects of forskolin, adenylate cyclase activator, on secretion of IGF-I have not been reported. Therefore, a modified perfused rat liver model was used to investigate the regulatory effects of forskolin on IGF-I secretion in this experiment. The results were summerized as follows : 1. Modified perfused rat liver model was not changed to aspartate aminotransferase(AST), alanine aminotransferase(ALT) and lactic dehydrogenase(LDH) secretion in time. 2. The IGF-I secretion in hepatic cell was increased by forskolin($10^{-5}$, $10^{-6}$ and $10^{-7}M$) in a dose-dependent manner as compared with those of the controls, and significantly increased by $10^{-5}$ and $10^{-6}$ forskolin(p < 0.05). 3. Secretion of glucose in hepatic cell significantly was decreased by $10^{-5}$ forskolin as compared with those of controls(p < 0.05). These results suggest that forskolin may be involved in the regulation of IGF-I secretion in the perfused rat liver.

• Clinical and Experimental Pediatrics
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• v.51 no.1
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• pp.47-53
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• 2008

Purpose : The serum levels of total insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 reflect endogenous growth hormone (GH) secretion in healthy children. Free form of IGF-I which is suggested to have more potent biological action than complex form of IGF-I. The aim of this study is to investigate the serum levels of free IGF-I and its clinical value in healthy children. Methods : Serum levels of total IGF-I and IGFBP-3 were determined in 494 healthy children (248 boys and 246 girls) by RIA and IRMA. Serum level of free IGF-I was determined in 206 healthy children (103 boys and 103 girls) by IRMA. Results : The free IGF-I level increased with age in both sex. The free IGF-I level increased continuously between 7 and 15 years of age in boys, but decrement was noted after 14 years of age in girls. Serum total IGF-I level also increased with age in similar pattern of that of free IGF-I. There were no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age in both sex. And there were significant correlations between the level of free IGF-I and total IGF-I and the ratio of total IGF-I/IGFBP-3, respectively. Conclusion : In healthy children, serum free IGF-I increased with age in both sex and high free IGF-I level may play an important role in pubertal growth spurt. Our results suggest that the increased serum free IGF-I level in puberty may reflect changes in total IGF-I rather than IGFBP-3. But free IGF-I does not have more clinical value than total IGF-I because of no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age.

• 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.

• 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.

• 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]

• Clinical and Experimental Reproductive Medicine
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• v.43 no.2
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• pp.97-101
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• 2016

Objective: Growth hormone and its mediator, insulin-like growth factor-1 (IGF-1), have been suggested to exert gonadotropic actions in both humans and animals. The present study was conducted to assess the relationship between serum IGF-1 concentration, seminal plasma concentration, and sperm parameter abnormalities. Methods: A total of 79 men were enrolled in this study from December 2011 to July 2012 and were prospectively analyzed. Patient parameters analyzed included age, body mass index, smoking status, urological history, and fertility history. Patients were divided into four groups based on their semen parameters: normal (A, n=31), abnormal sperm motility (B, n=12), abnormal sperm morphology (C, n=20), and two or more abnormal parameters (D, n=16). Patient seminal plasma and serum IGF-1 concentrations were determined. Results: Patient baseline characteristics were not significantly different between any of the groups. The serum IGF-1 levels in groups B, C, and D were significantly lower than the levels in group A; however, the seminal plasma IGF-1 levels were not significantly different between any of the groups. Conclusion: Men with abnormal sperm parameters had significantly lower levels of serum IGF-1 compared with men with normal sperm parameters. Seminal plasma IGF-1 levels, however, did not differ significantly between the groups investigated here. Further investigations will be required to determine the exact mechanisms by which growth hormone and IGF-1 affect sperm quality.

• Korean Journal of Human Ecology
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• v.9 no.1
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• pp.81-88
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• 2006

IGFs and IGFBPs have an important role in controlling glucose homeostasis. This study was conducted to investigate the changes of insulin-like growth factor(IGF)-I. IGF-II and IGF binding proteins (IGFBPs) on fasting and postprandial state in Korean diabetes, Twenty eight healthy subjects and fifty seven diabetic patients participated in this study. The healthy subjects were not knowingly suffered from any disease and were not receiving any medical treatment, and diabetic subjects were undergo medical treatment, continuously. Weight and height were measured and body mass index (BMI) was calculated as weight (kg) divided by the square of height (m2). Blood pressure was measured. Plasma lipid profiles were analyzed by enzymatic methods, plasma Insulin and glucose levels were measured in fasting and postprandial state, respectively. The levels of serum IGFs and IGFBP-3 were measured by radioimmunoassay (RIA). The levels of glucose and insulin were significantly higher in diabetes than normal subjects on fasting as well as postprandial state (p<0.0l). The levels of IGF-I was significantly lower in diabetes than normal subjects, however in postprandial state, there was no significant difference between diabetes and control subjects, The levels of IGF-II were significantly lower in diabetes than control subjects both fasting and postpradial state, The level of IGFBP-3 were not significantly different between diabetes and normal subjects. Fasting IGF-I, IGF-II and IGFBP-3 levels were positively correlated with those levels on postprandial state, fasting IGe levels of IGF-I levels were positively correlated with fasting insulin levels, and postprandial IGF-I levels were positively correlated with fasting glucose, postprandial insulin and postprandial insulin levels, plasma triglyceride levels were correlated with plasma triglyceride levels. The IGFBP-3 levels were not correlated with IGF components, glucose, insulin and plasma lipids, These results demonstrate that in diabetes, the components IGF-I/IGFBPs system were significantly correlated with plsma glucose and insulin levels both fasting and postprandial state.

• 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.

• 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.

• 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.