• BMB Reports
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• v.32 no.2
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• pp.196-202
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• 1999

The existence of the Ras-independent signal transduction pathway of insulin leading to DNA synthesis was investigated in Rat-1 fibroblasts overexpressing human insulin receptor (HIRc-B) using the single-cell microinjection technique. Microinjection of a dominant-negative mutant $Ras^{N17}$ protein into quiescent HIRc-B cells inhibited the DNA synthesis stimulated by insulin. Microinjection of oncogenic H-$Ras^{V12}$ protein ($H-Ras^{V12}$) (0.1 mg/ml) induced DNA synthesis by 35%, whereas that of control-injected IgG was induced by 20%. When the marginal amount of oncogenic H-$Ras^{V12}$ protein was coinjected with a dominant-negative mutant of the H-Ras protein ($Ras^{N17}$), DNA synthesis was 35% and 74% in the absence and presence of insulin, respectively. This full recovery of DNA synthesis by insulin suggests the existence of the Ras-independent pathway. The same recovery was observed in the cells coinjected with either H-$Ras^{V12}$ plus H-$Ras^{N17}$ plus SH2 domain of the p85 subunit of PI3-kinase ($p85^{SH2-N}$) or H-$Ras^{V12}$ plus H-$Ras^{N17}$ plus interfering anti-Shc antibody. When co-injected with a dominant-negative H-$Ras^{N17}$, the DNA synthesis induced by the Ras-independent pathway was blocked. These results indicate that the Ras-independent pathway of insulin leading to DNA synthesis exists, bypassing the p85 of PI3-kinase and Shc protein, and requires Rac1 protein.

• Journal of Integrative Natural Science
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• v.10 no.3
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• pp.137-140
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• 2017

Diabetes mellitus has become a major growing public health problem worldwide. More than 90% of all diabetes cases are classified as type 2 diabetes (T2D), which is also known as non-insulin dependent diabetes. Protein tyrosine phosphatase 1B (PTP1B) plays an important role in the negative regulation of insulin signal transduction pathway and has emerged as novel therapeutic strategy for the treatment of type 2 diabetes. PTP1B inhibitors enhance the sensibility of insulin receptor (IR) and have favorable curing effect for insulin resistance-related diseases. Recently twelve anti-diabetic xanthones were isolated from the bark of Garcinia xanthochymus. Hence, in the present study, molecular docking was carried out for these twelve xanthones. The objective of this work is to study the interaction of the newly isolated xanthones with PTP1B. The docking results showed that xanthones have good interactions and has better docking score with PTP1B and suggest LYS120 and ASP181 are the important residues involved in interaction between PTP1B enzyme and the xanthones.

• The Journal of the Korea Contents Association
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• v.9 no.4
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• pp.355-363
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• 2009

Increased oxidative stress by abnormal mitochondrial function can damage cell signal transduction and gene expression, and induce insulin resistance or diabetes. Autophagy, however, improve insulin resistance by clearance of malfunctioning mitochondria. Exercise also recovers the muscle dysfunction and degeneration by activating mitochondrial biogenesis. As it seems that exercise and autophagy might act as an orchestrated network to induce mitochondrial biogenesis, we investigated whether autophagy is involved in AMPK signal pathway stimulated by exercise or AICAR to increase mitochondrial biogenesis. And it showed that PGC-1 and mtTFA, but not autophagy marker LC3 mRNA expression were significantly increased by 6 hr of acute exercise. On the other hand, PGC-1 and mtTFA mRNA expression were upregulated by AICAR treatment to C2C12 myotube. However these genes were not inhibited by LC3 siRNA transfection. These results provide the evidence that autopahgy affects on mitochondrial biogenesis through different signal pathway from AMPK signal transduction.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.417-424
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• 2019

The aim of this study is to investigate the effect of Lespedeza maximowiczii var. tricolor Nakai (LMTN) on glucose metabolism. LMTN extract significantly enhanced the glucose uptake and lipid accumulation in 3T3-L1 adipocytes compared with control. Also, LMTN extract in 3T3-L1 adipocytes significantly increased the protein expression of peroxisome proliferator-activated receptor (PPAR)γ, insulin receptor substrate-1, and glucose transporter (GLUT)4. The regulatory effect on glucose uptake or insulin signal transduction of LMTM extract was lower than troglitazone or pinitol such as the positive control, but increased PPARγ activation. Additionally, LMTM extract has an insulin-mimetic effect. In db/db mice, LMTN extract (250 mg/kg BW) significantly reduced water and food intake, blood glucose, and level of plasma triglyceride and total cholesterol. Furthermore, the expression of PPARã and GLUT4 mRNA in adipose or muscle tissue effectively was increased by oral treatment of LMTN extract. Thus, our results suggest that LMTN extract improves the glucose metabolism through PPARγ and insulin-mimetic effect in 3T3-L1 adipocytes and db/db mice.

• BMB Reports
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• v.45 no.12
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• pp.700-706
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• 2012

Obesity is a worldwide epidemic as well as being a major risk factor for diabetes, cardiovascular diseases and several types of cancers. Obesity is mainly due to the overgrowth of adipose tissue arising from an imbalance between energy intake and energy expenditure. Adipose tissue, primarily composed of adipocytes, plays a key role in maintaining whole body energy homeostasis. In view of the treatment of obesity and obesity-related diseases, it is critical to understand the detailed signal transduction mechanisms of adipogenic differentiation. Adipogenic differentiation is tightly regulated by many key signal cascades, including insulin signaling. These signal cascades generally transfer or amplify the signal by using serial tyrosine phosphorylations. Thus, protein tyrosine kinases and protein tyrosine phosphatases are closely related to adipogenic differentiation. Compared to protein tyrosine kinases, protein tyrosine phosphatases have received little attention in adipogenic differentiation. This review aims to highlight the involvement of protein tyrosine phosphatases in adipogenic differentiation and the possibility of protein tyrosine phosphatases as drugs to target obesity.

• Korean Journal of Pharmacognosy
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• v.35 no.1 s.136
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• pp.16-21
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• 2004

Protein tyrosine phosphatase 1B(PTP1B) is thought to be a negative regulator in insulin signal-transduction pathway. Insulin-resistance by the activation of PTP1B is a hallmark of both type 2 diabetes and obesity. Thus, the compounds inhibiting PTP1B can improve insulin resistance and can be effective in treating type 2 diabetes and obesity. The methanol extracts of 160 herbal medicines were screened for the inhibitory activity against PTP1B. Among the tested extracts, methanol extracts of Amsonia elliptica, Areca catechu, Benincasa hispida, Morus alba, Salvia miltiorrhiza, Siegesbeckia orientalis, and Trichosanthes kirilowii showed relatively strong inhibitory activity against PTP1B.

• Development and Reproduction
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• v.20 no.3
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• pp.179-185
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• 2016

The insulin-like growth factor (IGF) pathway is a key signal transduction pathway involved in cell proliferation, migration, and apoptosis. In dairy cows, IGF family proteins and binding receptors, including their intracellular binding partners, regulate mammary gland development. IGFs and IGF receptor interactions in mammary glands influence the early stages of mammogenesis, i.e., mammary ductal genesis until puberty. The IGF pathway includes three major components, IGFs (such as IGF-I, IGF-II, and insulin), their specific receptors, and their high-affinity binding partners (IGF binding proteins [IGFBPs]; i.e., IGFBP1-6), including specific proteases for each IGFBP. Additionally, IGFs and IGFBP interactions are critical for the bioactivities of various intracellular mechanisms, including cell proliferation, migration, and apoptosis. Notably, the interactions between IGFs and IGFBPs in the IGF pathway have been difficult to characterize during specific stages of bovine mammary gland development. In this review, we aim to describe the role of the interaction between IGFs and IGFBPs in overall mammary gland development in dairy cows.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1532-1536
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• 2008

Quercetin which isolated form the roots of Houttuynia cordata. was determined on the basis of IR, ID and 2D NMR specta by direct comparison with authentic compounds. Protein tyrosine phophatase 1B (PTP1B) is thought to be a negative regulator in insulin signal-transduction pathway. Insulin-resistance by the activation of PTP1B is a hallmark of both type 2 diabetes and obesity. Thus, the compound inhibiting PTP1B can improve insulin resistance and can be effective in treating type 2 diabetes and obesity. Quercetin which measured the inhibitory activity against PTP1B was 92.1% inhibition in the 30 ${\mu}g$/mL, 83.4% inhibition in the 6 ${\mu}g$/mL and 76.5% inhibition in the 3 ${\mu}g$/mL. These results suggest that quercetin retains a potential PTP1B activity.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.12
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• pp.1785-1793
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• 2001

The interaction of growth hormone with it's receptor results in dimerization of receptor, a feature known in action of certain cytokines. The interaction results in generation of number of signalling molecules. The involvement of Janus kinases, mitogen activated kinases, signal transduction and activator of transcription proteins, insulin like substrate, phosphatidylinositol 3-kinase, phospholipase C, protein kinase C is almost established in growth hormone action. There are still many missing links in explaining diversified activities of growth hormone. Amino acid sequence data for growth hormones and growth hormone receptors from a number of species have proved useful in understanding species specific effects of growth hormone. Complete understanding of growth hormone action can have implications in designing drugs for obtaining desired effects of growth hormone.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.141-149
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• 2015

"G protein-coupled receptor 40" (GPR40), a receptor for long-chain fatty acids, mediates the stimulation of glucose-induced insulin secretion. We examined the profiles of differential gene expression in GPR40-activated cells treated with linoleic acid, and finally predicted the integral pathways of the cellular mechanism of GPR40-mediated insulinotropic effects. After constructing a GPR40-overexpressing stable cell line (RIN-40) from the rat pancreatic ${\beta}$-cell line RIN-5f, we determined the gene expression profiles of RIN-5f and RIN-40. In total, 1004 genes, the expression of which was altered at least twofold, were selected in RIN-5f versus RIN-40. Moreover, the differential genetic profiles were investigated in RIN-40 cells treated with $30{\mu}M$ linoleic acid, which resulted in selection of 93 genes in RIN-40 versus RIN-40 treated with linoleic acid. Based on the Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG, http://www.genome.jp/kegg/), sets of genes induced differentially by treatment with linoleic acid in RIN-40 cells were found to be related to mitogen-activated protein (MAP) kinase- and neuroactive ligand-receptor interaction pathways. A gene ontology (GO) study revealed that more than 30% of the genes were associated with signal transduction and cell proliferation. Thus, this study elucidated a gene expression pattern relevant to the signal pathways that are regulated by GPR40 activation during the acute period. Together, these findings increase our mechanistic understanding of endogenous molecules associated with GPR40 function, and provide information useful for identification of a target for the management of type 2 diabetes mellitus.