• Title/Summary/Keyword: insulin signaling pathway

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Exploring the quality standard of Phellinus spp through β-glucan content and sensory evaluation (β-glucan 함량과 관능검사를 통한 상황버섯 품질기준 모색)

  • Shin, Yong-Wook
    • The Korea Journal of Herbology
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    • v.32 no.4
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    • pp.47-52
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    • 2017
  • Objective : Phellinus spp. mushroom is an object of interest because it has excellent anticancer effect. Owing to the similalarities in the morphology, Phellinus linteus and Phellinus baumii are often used as same Sang Hwang Mushroom in the Korean market.. The quality control for mushrooms is needed because there are many differences in the efficacy according to cultivation method and cultivation area. Therefore, a reliable authentication method of these herbal medicine is necessary to compare and measure the amount of beta-glucan which is known to have a hypoglycemic effect, from the mushrooms collected in various regions Methods : 7 samples of medicinal mushrooms supplying phellinus spp. were collected in Korea, China and Cambodia. We investigated the hardness, colors, extract ratio, ${\alpha}-amylase$ and ${\alpha}-glucosidase$ inhibitory activities, glucose transporter 4 (GLUT-4) expressions of water extracts from Phellinus spp and also MTT assay were examined for cell toxicity. Results : The results revealed that Phellinus spp.water Ext.inhibited ${\alpha}-glucosidase$ activity. glucose transporter 4 (GLUT-4), the key insulin signaling pathway transcription factor, was remarkably increased by the Phellinus baumii water extract Conclusions : These results suggest that The more yellowish the mushroom is, the lower the hardness, the more the content of ${\beta}-glucan$ is proportional. Because the more ${\beta}-glucan$, the greater the effect of hypoglycemia. compared to the hypoglycemic effect, Phellinus Baumii grown at hanging on selves for 7 month in the green house is the best.

Fagopyritol, a Derivative of D-chiro-inositol, Induces GLUT4 Translocation via Actin Filament Remodeling in L6-GLUT4myc Skeletal Muscle Cells (랫드 근육세포에서 fagopyritol이 액틴 필라멘트 구조와 포도당 수송체 4에 미치는 영향)

  • Nam, Hajin;Hwang, In Koo;Jung, Harry;Kwon, Seung-Hae;Park, Ok Kyu;Suh, Jun Gyo
    • Journal of Life Science
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    • v.23 no.9
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    • pp.1163-1169
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    • 2013
  • Insulin induces glucose transporter 4 (GLUT4) translocation to the muscle cell surface. As fagopyritol has insulin-like effects, the effects of fagopyritol on GLUT4 translocation and filamentous (F) actin remodeling in L6-GLUT4myc skeletal muscle cells were investigated. Fagopyritol significantly increased plasma membrane GLUT4 levels compared with the basal control in L6-GLUT4myc myoblast cells. Phosphatidylinositol (PI) 3-kinase inhibitor (LY294002) treatment prevented GLUT4 translocation to the plasma membrane in the myoblasts. Fagopyritol treatment apparently stimulates F-actin remodeling in myoblasts. In addition, fagopyritol treatment induced GLUT4 translocation and F-actin remodeling in myotubes. Taken together, these results suggest that fagopyritol promotes GLUT4 translocation and F-actin remodeling by activating the PI 3-kinase-dependent signaling pathway.

Anti-diabetic effect of mulberry leaf extract fermented with Lactobacillus plantarum (Lactobacillus plantarum으로 발효한 뽕잎 추출물의 항당뇨 효과)

  • Choi, Jisu;Lee, Sulhee;Park, Young-Seo
    • Korean Journal of Food Science and Technology
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    • v.52 no.2
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    • pp.191-199
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    • 2020
  • The purpose of this study was to isolate novel lactic acid bacteria to ferment mulberry leaf extract (MLE) and to investigate its anti-diabetic effect. Lactobacillus plantarum SG-053 isolated from gatkimchi was selected to ferment MLE because it exhibited high α-glucosidase inhibitory activity (96.8%) and enhanced the content of 1-deoxynojirimycin (DNJ), an anti-diabetic substance, in fermented MLE up-to 2.2 times. MLE fermented with L. plantarum SG-053 (FMLE) showed growth promoting activity against L6 myotubes and increased the gene expressions of IRS-1, PI3K p85α, and GLUT-4 up-to 1.4, 2.2, and 1.4 times, respectively, and 2-deoxyglucose uptake up-to 40.7%. In rat skeletal muscle tissue, the expressions of PI3K p85α and GLUT-4 increased by 6.4 and 2.1 times, respectively. These results suggest that L. plantarum SG-053 could enhance the DNJ content of MLE by fermentation and that FMLE is effective in ameliorating insulin resistance via activation of the insulin signaling pathway.

Betulinic Acid Stimulates Glucose Uptake through the Activation of PI3K and AMPK in 3T3-L1 Adipocytes (Betulinic acid의 PI3K와 AMPK경로 활성화를 통한 3T3-L1 지방세포에서 포도당 흡수 촉진 효과)

  • Lee, Jung Kyung;Park, Jae Eun;Han, Ji Sook
    • Journal of Life Science
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    • v.32 no.10
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    • pp.762-770
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    • 2022
  • Hyperglycemia in type 2 diabetes can be alleviated by promoting cellular glucose uptake. Betulinic acid (3β,-3-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic lupane-type triterpenoid compound. Although there have been studies on the antidiabetic activity of betulinic acid, studies on cellular glucose uptake are lacking. We investigated the effects of betulinic acid on glucose uptake and its mechanism of action in 3T3-L1 adipocytes. Betulinic acid significantly stimulated glucose uptake in 3T3-L1 adipocytes by increasing the phosphorylation of the insulin receptor substrate 1-tyrosine (IRS-1tyr) in the insulin signaling pathway, which in turn stimulated the activation of phosphoinositide 3-kinase (PI3K) and the phosphorylation of protein kinase B (Akt). The activation of PI3K and Akt by betulinic acid translocated glucose transporter 4 to the plasma membrane (PM-GLUT4), thereby increasing the expression of PM-GLUT4 and thus stimulating cellular glucose uptake. Betulinic acid also significantly increased the phosphorylation/activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. The activation of PI3K and AMPK by betulinic acid was confirmed using the PI3K inhibitor wortmannin and the AMPK inhibitor compound C. The increase in glucose uptake induced by betulinic acid was significantly decreased by wortmannin and compound C in the 3T3-L1 adipocytes. These results suggest that betulinic acid stimulates glucose uptake by activating PI3K and AMPK in 3T3-L1 adipocytes.

Beneficial Effects of Acanthopanax senticosus Extract in Type II Diabetes Animal Model via Down-Regulation of Advanced Glycated Hemoglobin and Glycosylation End Products (제2형 당뇨 동물모델에서 가시오가피 추출물의 당화혈색소 및 최종당화산물 억제를 통한 혈당조절 효과)

  • Kwon, Han Ol;Lee, Minhee;Kim, Yong Jae;Kim, Eun;Kim, Ok-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.7
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    • pp.929-937
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    • 2016
  • The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

Anti-obesity and Anti-diabetic Effects of the Fermented Ethanol Extracts from White Jelly Fungus (Tremella fuciformis Berk) with Lactobacillus rhamnosus BHN-LAB 76 (Lactobacillus rhamnosus BHN-LAB 76로 발효한 흰목이버섯 (Tremella fuciformis Berk) 추출물의 항비만 및 항당뇨 효과)

  • Yoon, Yeo-Cho;Kim, Byung-Hyuk;Kim, Jung-Gyu;Lee, Jun-Hyeong;Park, YeEun;Park, Hye-Suk;Hwang, Hak-Soo;Kwon, Gi-Seok;Lee, Jung-Bok
    • Microbiology and Biotechnology Letters
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    • v.47 no.3
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    • pp.323-331
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    • 2019
  • White jelly fungus (Tremella fuciformis Berk; TF) has been used as a traditional medicine in Asia; it is known to prevent hypertension, aging, cancer, and arteriosclerosis. This study aimed to investigate the anti-diabetic effects of fermented Tremella fuciformis Berk (FTF) ethanol extracts fermented with L. rhamnosus BHN-LAB 76. We show that FTF increases the ${\alpha}$-glucosidase inhibitory activity and suppress the adipogenesis of 3T3-L1 adipocytes. These inhibitory effects of FTF are accompanied by the regulation of the phosphorylation of AMPK, JNK, and Akt. These data demonstrate that FTF not only inhibits adipogenesis by affecting the adipogenic signaling, but also increases the anti-diabetic effects by regulating the insulin signaling pathway. Therefore, we suggest that the FTF can be used for developing functional food and cosmetics materials.

Gene Expression Profiling of Acetaminophen Induced Hepatotoxicity in Mice

  • Suh, Soo-Kyung;Jung, Ki-Kyung;Jeong, Youn-Kyoung;Kim, Hyun-Ju;Lee, Woo-Sun;Koo, Ye-Mo;Kim, Tae-Gyun;Kang, Jin-Seok;Kim, Joo-Hwan;Lee, Eun-Mi;Park, Sue-Nie;Kim, Seung-Hee;Jung, Hai-Kwan
    • Molecular & Cellular Toxicology
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    • v.2 no.4
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    • pp.236-243
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    • 2006
  • Microarray analysis of gene expression has become a powerful approach for exploring the biological effects of drugs, particularly at the stage of toxicology and safety assessment. Acetaminophen (APAP) has been known to induce necrosis in liver, but the molecular mechanism involved has not been fully understood. In this study, we investigated gene expression changes of APAP using microarray technology. APAP was orally administered with a single dose of 50 mg/kg or 500 mg/kg into ICR mice and the animals were sacrificed at 6, 24 and 72 h of APAP administration. Serum biochemical markers for liver toxicity were measured to estimate the maximal toxic time and hepatic gene expression was assessed using high-density oligonucleotide microarrays capable of determining the expression profile of >30,000 well-substantiated mouse genes. Significant alterations in gene expression were noted in the liver of APAP-administered mice. The most notable changes in APAP-administered mice were the expression of genes involved in apoptosis, cell cycle, and calcium signaling pathway, cystein metabolism, glutatione metabolism, and MAPK pathway. The majority of the genes upregulated included insulin-like growth factor binding protein 1, heme oxygenase 1, metallothionein 1, S100 calcium binding protein, caspase 4, and P21. The upregulation of apoptosis and cell cycle-related genes were paralleled to response to APAP. Most of the affected gene expressions were returned to control levels after 72 hr. In conclusion, we identified potential hepatotoxicity makers, and these expressions profiling lead to a better understanding of the molecular basis of APAP-induced hapatotoxicity.

Effects of Baicalin on Gene Expression Profiles during Adipogenesis of 3T3-L1 Cells (3T3-L1 세포의 지방세포형성과정에서 Baicalin에 의한 유전자 발현 프로파일 분석)

  • Lee, Hae-Yong;Kang, Ryun-Hwa;Chung, Sang-In;Cho, Soo-Hyun;Yoon, Yoo-Sik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.1
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    • pp.54-63
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    • 2010
  • Baicalin, a flavonoid, was shown to have diverse effects such as anti-inflammatory, anti-cancer, anti-viral, anti-bacterial and others. Recently, we found that the baicalin inhibits adipogenesis through the modulations of anti-adipogenic and pro-adipogenic factors of the adipogenesis pathway. In the present study, we further characterized the molecular mechanism of the anti-adipogenic effect of baicalin using microarray technology. Microarray analyses were conducted to analyze the gene expression profiles during the differentiation time course (0 day, 2 day, 4 day and 7 day) in 3T3-L1 cells with or without baicalin treatment. We identified a total of 3972 genes of which expressions were changed more than 2 fold. These 3972 genes were further analyzed using hierarchical clustering analysis, resulting in 20 clusters. Four clusters among 20 showed clearly up-regulated expression patterns (cluster 8 and cluster 10) or clearly down-regulated expression patterns (cluster 12 and cluster 14) by baicalin treatment for over-all differentiation period. The cluster 8 and cluster 10 included many genes which enhance cell proliferation or inhibit adipogenesis. On the other hand, the cluster 12 and cluster 14 included many genes which are related with proliferation inhibition, cell cycle arrest, cell growth suppression or adipogenesis induction. In conclusion, these data provide detailed information on the molecular mechanism of baicalin-induced inhibition of adipogenesis.

Anti-obesity Effect of Salsola collina Ethanol Extract (솔장다리 추출물의 항비만 효과)

  • Jin, Kyong-Suk;Lee, Su Hyeon;Kwon, Hyun Ju;Kim, Byung Woo
    • Journal of Life Science
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    • v.27 no.8
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    • pp.888-895
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    • 2017
  • Salsola collina (S. collina) is an annual plant widely distributed in drought and semi-drought areas, which has been used for a long time as a kind of folk remedy in traditional Chinese medicine for the treatment of hypertension. Previously, the anti-oxidative and anti-cancer activities of S. collina were elucidated in our research group. In this study, the anti-obesity activities of S. collina ethanol extract (SCEE) were evaluated using a pancreatic lipase enzyme inhibition assay and cell culture model. The results showed that SCEE effectively suppressed pancreatic lipase enzyme activity in a dose-dependent manner. Furthermore, SCEE significantly suppressed adipocyte differentiation, lipid accumulation, and triglyceride (TG) content, and triggered lipolysis on insulin, dexamethasone, and 3-isobutyl-l-methylxanthine-treated 3T3-L1 preadipocytes in a dose-dependent manner without cytotoxicity. Its anti-obesity effect was modulated by cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, and the peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) gene, as well as protein expressions. Taken together, these results offer the important new insight that S. collina possesses anti-obesity properties, such as pancreatic lipase inhibition and anti-adipogenic and lipolysis effects through the modulation of their upstream signaling pathway. It could become a promising source in the field of nutraceuticals, and the identification of active compounds that confer the biological activities of SCEE may be needed.

Molecular Analysis of Alternative Transcripts of the Equine Cordon-Bleu WH2 Repeat Protein-Like 1 (COBLL1) Gene

  • Park, Jeong-Woong;Jang, Hyun-Jun;Shin, Sangsu;Cho, Hyun-Woo;Choi, Jae-Young;Kim, Nam-Young;Lee, Hak-Kyo;Do, Kyong-Tak;Song, Ki-Duk;Cho, Byung-Wook
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.6
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    • pp.870-875
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    • 2015
  • The purpose of this study was to investigate the alternative splicing in equine cordon-bleu WH2 repeat protein-like 1 (COBLL1) gene that was identified in horse muscle and blood leukocytes, and to predict functional consequences of alternative splicing by bioinformatics analysis. In a previous study, RNA-seq analysis predicted the presence of alternative spliced isoforms of equine COBLL1, namely COBLL1a as a long form and COBLL1b as a short form. In this study, we validated two isoforms of COBLL1 transcripts in horse tissues by the real-time polymerase chain reaction, and cloned them for Sanger sequencing. The sequencing results showed that the alternative splicing occurs at exon 9. Prediction of protein structure of these isoforms revealed three putative phosphorylation sites at the amino acid sequences encoded in exon 9, which is deleted in COBLL1b. In expression analysis, it was found that COBLL1b was expressed ubiquitously and equivalently in all the analyzed tissues, whereas COBLL1a showed strong expression in kidney, spinal cord and lung, moderate expression in heart and skeletal muscle, and low expression in thyroid and colon. In muscle, both COBLL1a and COBLL1b expression decreased after exercise. It is assumed that the regulation of COBLL1 expression may be important for regulating glucose level or switching of energy source, possibly through an insulin signaling pathway, in muscle after exercise. Further study is warranted to reveal the functional importance of COBLL1 on athletic performance in race horses.