• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.100-100
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• 2001

Hypoxia is a pathophysiological condition that occurs during injury, ischemia, and stroke. Hypoxic stress induces the expression of genes associated with increased energy flux, including the glucose transporters Glutl and Glut3, several glycolytic enzymes, nitric oxide synthase, erythropoietin and vascular endothelial growth factor. Induction of these genes is mediated by a common basic helix-loop-helix PAS transcription complex, the hypoxia-inducible factor-l${\alpha}$ (HIF-1${\alpha}$)/ aryl hydrocarbon receptor nuclear translocator (ARNT). Insulin plays a central role in regulating metabolic pathways associated with energy storage and utilization. It triggers the conversion of glucose into glycogen and triglycerides and inhibits gluconeogenesis. Insulin also induced hypoxia-induced genes. However the underlying mechanism is unestablished. Here, we study the possibility that transcription factor HIF-1${\alpha}$ is involved in insulin-induced gene expression. We investigate the mechanism that regulates hypoxia-inducible gene expression In response to insulin We demonstrate that insulin increases the transcription of hypoxia- inducible gene. Insulin-induced transcription is not detected in Arnt defective cell lines. Under hypoxic condition, HIF- l${\alpha}$ stabilizes but does not under insulin treatment. Insulin-induced gene expression is inhibited by presence of PI-3 kinase inhibitor and Akt dominant negative mutant, whereas hypoxia-induced gene expression is not. ROS inhibitor differently affects insulin-induced gene expressions and hypoxia-induced gene expressions. Our results demonstrate that insulin also regulates hypoxia-inducible gene expression and this process is dependent on Arnt. However we suggest HIF-l${\alpha}$ is not involved insulin-induced gene expression and insulin- and hypoxia- induces same target genes via different signaling pathway.

• Biomolecules & Therapeutics
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• v.25 no.1
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• pp.1-3
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• 2017

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2004.05a
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• pp.90-90
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• 2004

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.199-199
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• 2001

• Journal of Applied Biological Chemistry
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• v.64 no.1
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• pp.89-96
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• 2021

The aim of this study is to examine the effect of Caulerpa okamurae ethanol extract (COE) on glucose metabolism and insulin sensitivity as one of the drug targets for treatment of type2 diabetes. COE significantly inhibited protein tyrosine phosphatase (PTP1B) and dipeptidyl peptidase-IV (DPP-IV) enzyme activities in vitro assay. Also, COE significantly enhanced the glucose uptake and the expression of insulin receptor substrate-1 (IRS-1) and glucose transporter4 (GLUT4) proteins in 3T3-L1 adipocytes or zebrafish larvae compared with control. In dexamethasone-induced resistance model of L6 myotubes, the protein expression of insulin signaling and glucose uptake was effectively increased by the treatment of COE. In contrast, the elevated phosphorylation of IRS-1 Ser307 was normally suppressed by treatment of COE. However, COE had no effect on insulin secretion in pancreatic beta cells. Thus, our results suggest that COE improves the glucose metabolism and insulin sensitivity through the regulation of insulin signaling and GLUT4 protein in insulin's target cells and zebrafish larvae.

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.267-273
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• 2011

Syndecans are membrane-anchored proteoglycans and implicated in the pathogenesis of cancer progression and metastasis. Syndecans also play important roles in interacting with growth factors, extracellular matrix and other cell surface molecules such as IGF-1 receptor. In the present review, we discuss about the syndecan structure, their role in signaling with other receptors, in addition to its general biology. The emerging roles of syndecans in the pathophysiology of human diseases, especially insulin resistance, diabetes and cancer is discussed.

• Journal of Pharmacopuncture
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• v.26 no.4
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• pp.319-326
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• 2023

Objectives: The study's goal was to find out whether Chrysanthemum rubellum extract has anti-diabetic properties by concentrating on α-glucosidase and the PTP-1B signaling pathway. C. rubellum flowers were used for extraction using Methanol/water (80/20) as solvent. Methods: LC-MS techniques was used to check the presence of phytoconstituents present in C. rubellum extract. In vitro antidiabetic activity was evaluated using α-glucosidase inhibitory activity and PTP-1B signaling pathway. On Streptozotocin (STZ)-induced rats with diabetes, the in vivo antidiabetic efficacy was assessed using a test for oral glucose tolerance. Results: The phytoconstituents identified in the extract of C. rubellum were apigenin, diosmin, myricetin, luteolin, luteolin-7-glucoside, and Quercitrin as compound 1-6, respectively. Results showed that diosmin exhibited highest α-glucosidase inhibitory activity i.e. 90.39%. The protein level of PTP-1B was lowered and the insulin signalling activity was directly increased by compounds 1-6. The maximum blood glucose levels were seen in all groups' OGTT findings at 30 minutes following glucose delivery, followed by gradual drops. In comparison to the control group, the extract's glucose levels were 141 mg/dL at 30 minutes before falling to 104 mg/dL after 120 minutes. The current study has demonstrated, in summary, that extract with phytoconstituents reduce blood sugar levels in rats. Conclusion: This finding suggests that extract may reduce the chance of insulin resistance and shield against disorders like hyperglycemia.

• Journal of Life Science
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• v.25 no.1
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• pp.8-15
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• 2015

The peroxisome proliferator-activated receptor (PPAR) signaling pathway is well known as a candidate pathway related to meat quality in mammals. In particular, there are many studies on the relationship between the PPAR signaling pathway and intramuscular fat. However, recent studies have demonstrated that genes in the PPAR signaling pathway are associated with carcass weight in cattle. Among 48 genes in the PPAR signaling pathway, 16 genes are related to the insulin that regulates the adipocyte glucose metabolism and thus affects body weight. Therefore, we conducted an investigation to try to identify candidate genes associated with the carcass weight and relationships between the expressions of these 16 genes in the loin muscle of Hanwoo (Korean cattle). From regression analysis, the three genes (ACSL6, FADS2, and ILK) showed significant effects with regard to carcass weight (p<0.05). Finally, we analyzed the common regulators of the significant genes from pathway analysis. The significant genes are regulated by insulin as well as D-glucose. These findings show that the differentially expressed genes are possible candidate genes associated with carcass weight in the longissimus muscle of Korean cattle.

• Nutrition Research and Practice
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• v.7 no.6
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• pp.439-445
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• 2013

It has been shown that dysregulation of IGF-1 signaling is associated with tumor incidence and progression, whereas blockade of the signaling can effectively inhibit carcinogenesis. Although several mechanisms of anticancer activity of quercetin were proposed, molecular targets of quercetin have not been identified yet. Hence, we assessed the effect of quercetin on IGF-1 signaling inhibition in BK5.IGF-1 transgenic (Tg) mice, which over-expresses IGF-1 in the skin epidermis. A quercetin diet (0.02% wt/wt) for 20 weeks remarkably delayed the incidence of skin tumor by 2 weeks and reduced tumor multiplicity by 35% in a 7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two stage mouse skin carcinogenesis protocol. Moreover, skin hyperplasia in Tg mice was significantly inhibited by a quercetin supplementation. Further analysis of the MT1/2 skin papilloma cell line showed that a quercetin treatment dose dependently suppressed IGF-1 induced phosphorylation of the IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1, Akt and S6K; however, had no effect on the phosphorylation of PTEN. Additionally, the quercetin treatment inhibited IGF-1 stimulated cell proliferation in a dose dependent manner. Taken together, these data suggest that quercetin has a potent anticancer activity through the inhibition of IGF-1 signaling.

• 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.