• BMB Reports
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• 제42권10호
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• pp.655-660
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• 2009

The potential anti-metastasis and anti-invasion activities of early growth response gene-1 (Egr-1) and claudin-3, a tight junction (TJ)-related protein, were evaluated using histone deacetylase (HDAC) inhibitors in human hepatocarcinoma cells. The results of wound healing and Transwell assays showed that HDAC inhibitors such as trichostatin A and sodium butyrate inhibited cell migration and invasion. HDAC inhibitors markedly induced Egr-1 expression during the early period, after which expression levels decreased. In addition, the down-regulation of snail and type 1 insulin-like growth factor receptor (IGF-1R) in HDAC inhibitor- treated cells induced the upregulation of thrombospondin-1 (TSP-1), E-cadherin and claudin-3. Cells transfected with Egr-1 and claudin-3 siRNA displayed significant blockage of HDAC inhibitor-induced anti-invasive activity. Collectively, these findings indicate that the up-regulation of Egr-1 and claudin-3 are crucial steps in HDAC inhibitor-induced anti-metastasis and anti-invasion.

• Nutrition Research and Practice
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• 제7권3호
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• pp.166-171
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• 2013

The purpose of this study was to investigate the effects of lotus leaf on hyperglycemia and dyslipidemia in animal model of diabetes. Inhibitory activity of ethanol extract of lotus leaf against yeast ${\alpha}$-glucosidase was measured in vitro. The effect of lotus leaf on the postprandial increase in blood glucose levels was assessed in streptozotocin-induced diabetic rats. A starch solution (1 g/kg) with and without lotus leaf extract (500 mg/kg) was administered to the rats after an overnight fast, and postprandial plasma glucose levels were monitored. Four-week-old db/db mice were fed a basal diet or a diet containing 1% lotus leaf extract for 7 weeks after 1 week of acclimation to study the chronic effect of lotus leaf. After sacrifice, plasma glucose, insulin, triglycerides (TG), total cholesterol (CHOL), high-density lipoprotein (HDL)-CHOL, and blood glycated hemoglobin levels were measured. Lotus leaf extract inhibited ${\alpha}$-glucosidase activity by 37.9%, which was 1.3 times stronger than inhibition by acarbose at a concentration of 0.5 mg/mL in vitro. Oral administration of lotus leaf extract significantly decreased the area under the glucose response curve by 35.1% compared with that in the control group (P < 0.01). Chronic feeding of lotus leaf extract significantly lowered plasma glucose and blood glycated hemoglobin compared with those in the control group. Lotus leaf extract significantly reduced plasma TG and total CHOL and elevated HDL-CHOL levels compared with those in the control group. Therefore, we conclude that lotus leaf is effective for controlling hyperglycemia and dyslipidemia in an animal model of diabetes mellitus.

• 한국생활과학회지
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• 제23권1호
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• pp.137-148
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• 2014

고지방식이에 의해 경중 정도의 비만과 당뇨가 유발되는 제2형 당뇨동물 모델인 C57BL/6J-ob/ob 마우스에서 콩 이소플라본 단독 또는 콩 이소플라본과 올리고당을 첨가한 우유 아이스크림이 당뇨지표에 미치는 영향을 조사함으로써 콩 이소플라본 첨가 아이스크림의 항당뇨 효능을 조사하였다. 5주령 된 C57BL/6J-ob/ob 수컷 마우스를 1주일간 적응시킨 후 대조군과 설탕 첨가 아이스크림(MS), 콩 이소플라본 첨가 아이스크림(MS-SI), 콩 이소플라본/프럭토올리고당 첨가 아이스크림(MF-SI)을 대조식이에 30% 첨가하여 12주 동안 자유롭게 섭취시켰다. 희생 후 당뇨 지표에 해당하는 경구 당부하 혈당 반응, 공복혈당, 인슐린, C-peptide, $HbA_{1c}$ 및 렙틴 농도와 중성지방, 그리고 비장세포 증식능과 비장세포에서 분비되는 사이토카인인 IL-6과 TNF-${\alpha}$에 미치는 효과를 측정한 결과 군간 유의한 차이를 보이지 않았다. 결론적으로 제2형 당뇨모델 마우스에서 우유 아이스크림에 첨가된 콩 이소플라본이 당뇨 지표에 긍정적인 효과를 나타내지 않았다.

• Child Health Nursing Research
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• 제21권2호
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• pp.176-182
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• 2015

Purpose: The study purposes were to explore school nurses' experience, perceived barriers, and education needs in diabetes management at school. Methods: This study was a cross sectional study and the study participants were recruited conveniently at continuing education seminars for school nurses at Incheon Metropolitan City. Results: Data for 101 school nurses were analyzed. The nurses were all women and their mean age was $46.9{\pm}9.3$ years. About 66% of them had experience with children with diabetes at school. The school nurses reported that 74.6% of the students tested their blood glucose by themselves, the school clinic was the most common place for blood glucose tests (47.8%) and insulin injections (50.8%) and the nurses knew students' diagnosis through the student health survey (58.2%). About half of the nurses (53.7%) reported that glucagon should be available at school and 49.2% were willing to inject glucagon when necessary. The most frequently reported barrier in diabetes management was role confusion ($6.0{\pm}1.3$) and the most common educational need was emergency responses ($5.9{\pm}1.4$). Conclusions: School health policy for diabetes management and diabetes resources are necessary to minimize role confusion of school nurses, improve emergency response, and facilitate health promotion activities in diabetes management.

• Asian-Australasian Journal of Animal Sciences
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• 제15권7호
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• pp.1026-1030
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• 2002

A trial was conducted to investigate the effect of dietary NMA on several growth associated hormones and fat metabolism in finishing pigs. A total of 84 crossbred finishing pigs (average initial BW of $56{\pm}$0.37kg) were divided into 6 pens, 14 pigs per pen (7 gilts and 7 barrows per pen). 3 pens of pigs were fed with control diet (corn-soybean meal) and the others were fed control diet addition with 50 mg/kg NMA. During the trial, all pigs were given free access to feed and water. After 44 days trial, 8 pigs from each treatment (4 gilts and 4 barrows, weight similar to average group weight, $86.94{\pm}0.71kg$ for control group, and $90.55{\pm}1.51kg$ for NMA treated group) were sacrificed to collect the sample of the liver, longissimus muscle, subcutaneous fat (10th rib). The addition of NMA in diet increased the IGF-I, Insulin, T3, T4 levels in serum by 50.68% (p<0.05), 38.36% (p<0.05), 123.33% (p<0.01), 60.58% (p<0.03), respectively. Meanwhile, IGF-I level in the liver and the muscle were increased with 17.83% (p<0.03) and 26.00% (p<0.03) with addition of NMA. The data from subcutaneous fat (10th rib) analysis showed that supplement of 50 mg/kg NMA decreased the total activities of malic dehydrogenase (MDH) by 20.54% (p<0.05), glucose-6- phosphate dehydrogenase (G-6-DPH) by 16.97% (p<0.05), and decreased the specific activities of MDH and G-6-DPH by 37.46% (p<0.01) and 35.06% (p<0.01), respectively. The hormone sensitive lipase (HSL) total activity was increased by 25.00% (p<0.05) in NMA treated pigs. These results indicated that addition of 50 mg/kg NMA to diet can induce the endocrine great change in finishing pigs, furthermore, inhibit the fat synthesis through suppressing lipogenic enzymes and promote the fat degradation by elevating HSL activity in finishing pigs.

• Asian-Australasian Journal of Animal Sciences
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• 제28권4호
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• pp.573-583
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• 2015

B-32 is one of a panel of monoclonal anti-idiotypic antibodies to growth hormone (GH) that we developed. To characterize and identify its potential role as a novel growth hormone receptor (GHR) agonist, we determined that B-32 behaved as a typical $Ab2{\beta}$ based on a series of enzyme-linked immunosorbent assay assays. The results of fluorescence-activated cell sorting, indirect immunofluorescence and competitive receptor binding assays demonstrated that B-32 specifically binds to the GHR expressed on target cells. Next, we examined the resulting signal transduction pathways triggered by this antibody in primary porcine hepatocytes. We found that B-32 can activate the GHR and Janus kinase (2)/signal transducers and activators of transcription (JAK2/STAT5) signalling pathways. The phosphorylation kinetics of JAK2/STAT5 induced by either GH or B-32 were analysed in dose-response and time course experiments. In addition, B32 could also stimulate porcine hepatocytes to secrete insulin-like growth factors-1. Our work indicates that a monoclonal anti-idiotypic antibody to GH (B-32) can serve as a GHR agonist or GH mimic and has application potential in domestic animal (pig) production.

• Nutrition Research and Practice
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• 제9권3호
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• pp.262-267
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• 2015

BACKGROUND/OBJECTIVES: The primary objective of the treatment of diabetes mellitus is the attainment of glycemic control. Hyperglycemia increases oxidative stress which contributes to the progression of diabetic complications. Thus, the purpose of this study was to investigate the hypoglycemic and antioxidant effects of Daraesoon (Actinidia arguta shoot) in animal models of diabetes mellitus. MATERIALS/METHODS: Rats with streptozotocin-induced diabetes received an oral administration of a starch solution (1 g/kg) either with or without a 70% ethanol extract of Daraesoon (400 mg/kg) or acarbose (40 mg/kg) after an overnight fast and their postprandial blood glucose levels were measured. Five-week-old C57BL/6J mice were fed either a basal or high-fat/high-sucrose (HFHS) diet with or without Daraesoon extract (0.4%) or acarbose (0.04%) for 12 weeks after 1 week of adaptation to determine the effects of the chronic consumption of Daraesoon on fasting hyperglycemia and antioxidant status. RESULTS: Compared to the control group, rats that received Daraesoon extract (400 mg/kg) or acarbose (40 mg/kg) exhibited a significant reduction in the area under the postprandial glucose response curve after the oral ingestion of starch. Additionally, the long-term consumption of Daraesoon extract or acarbose significantly decreased serum glucose and insulin levels as well as small intestinal maltase activity in HFHS-fed mice. Furthermore, the consumption of Daraesoon extract significantly reduced thiobarbituric acid reactive substances and increased glutathione levels in the livers of HFHS-fed mice compared to HFHS-fed mice that did not ingest Daraesoon. CONCLUSIONS: Daraesoon effectively suppressed postprandial hyperglycemia via the inhibition of ${\alpha}$-glucosidase in STZ-induced diabetic rats. Chronic consumption of Daraesoon alleviated fasting hyperglycemia and oxidative stress in mice fed a HFHS diet.

• The Korean Journal of Physiology and Pharmacology
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• 제24권5호
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• pp.395-402
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• 2020

This study has investigated the effect of a potent bioflavonoid, troxerutin, on diabetes-induced changes in pro-inflammatory mediators and expression of microRNA-146a and nuclear factor-kappa-B (NF-κB) signaling pathway in aortic tissue of type-I diabetic rats. Male Wistar rats were randomly divided into four groups (n = 6/each): healthy, healthy-troxerutin, diabetic, and diabetic-troxerutin. Diabetes was induced by streptozotocin injection (60 mg/kg; intraperitoneally) and lasted 10 weeks. Troxerutin (150 mg/kg/day) was administered orally for last month of experiment. Inflammatory cytokines IL-1β, IL-6, and TNF-α, as well as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), cyclooxygenase-II (COX-II), and inducible-nitric oxide synthase (iNOS) were measured on aortic samples by enzyme-linked immunosorbent assay. Gene expressions for transcription factor NF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), TNF receptor-associated factor-6 (TRAF-6), and microRNA-146a were determined using real-time polymerase chain reaction. Ten-week diabetes significantly increased mRNA levels of IRAK-1, TRAF-6, NF-κB, and protein levels of cytokines IL-1β, IL-6, TNF-α, adhesion molecules ICAM-1, VCAM, and iNOS, COX-II, and decreased expression of microRNA-146a as compared with healthy rats (p < 0.05 to p < 0.01). However, one month treatment of diabetic rats with troxerutin restored glucose and insulin levels, significantly decreased expression of inflammatory genes and pro-inflammatory mediators and increased microRNA level in comparison to diabetic group (p < 0.05 to p < 0.01). In healthy rats, troxerutin had significant reducing effect only on NF-κB, TNF-α and COX-II levels (p < 0.05). Beside slight improvement of hyperglycemia, troxerutin prevented the activation of NF-κB-dependent inflammatory signaling in the aorta of diabetic rats, and this response may be regulated by microRNA-146a.

• 대한본초학회지
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• 제31권6호
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• pp.29-35
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• 2016

Objectives : Blood stasis (BS) is related to be caused by blood circulation and stagnation which are cancer, atherosclerosis and hyperlipidemia in traditional medicine. We extracted 3 kinds of BS formula; Seogakjihwang-tang (SGT), Tonggyuhawlhyul-tang (THT), Hyulbuchukeo-tang (HCT). This study was conducted to investigate whether the 3 kinds of herbal formula extracts have inhibitory efficacy association with anti-adipogenesis. Methods : To investigate the anti-adipogenesis, we used the mouse fibroblast cell line, 3T3-L1 which differentiated into adipocytes in response to insulin, IBMX and dexamethasone (MDI). Cytotoxicity of herbal formula extracts were examined by CCK-8 kit. Intracellular lipid droplets were detected by Oil-Red-O staining. Triglyceride (TG) and leptin were measure using elisa kit. Results : The yield of water extracts was 14.62% (SGT), 21.27% (THT), 20.02% (HCT). Lipid accumulation was reduced significantly by 3 kinds of herbal formula compared to control. Especially, THT and HCT decreased lipid droplet, respectively at all concentration. The TG and leptin were also inhibited by 3 kinds of herbal formula. The IC50 of TG were $280.51{\mu}g/m{\ell}$ (SGT), $52.62{\mu}g/m{\ell}$ (THT), $313.99{\mu}g/m{\ell}$ (HCT). The IC50 of leptin were $348.76{\mu}g/m{\ell}$ (SGT), $164.02{\mu}g/m{\ell}$ (THT), $257.00{\mu}g/m{\ell}$ (HCT). THT was better than other herbal formula on anti-adipogenesis. Conclusion : kinds of herbal formula inhibited adipogenesis in MDI-induced 3T3-L1 adipocytes, as indicated by the significant reduction in TG and leptin concentration without cytotoxicity. Therefore, 3 kinds of herbal formula for BS might act as a therapeutic agent for preventing lipid diseases, such as obesity and atherosclerosis.

• Archives of Pharmacal Research
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• 제27권7호
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• pp.806-810
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• 2004

Metformin is a biguanide antihyperglycemic agent often used for the treatment of non-insulin dependent diabetics (NIDDM). In this study, the pharmacokinetics and pharmacodynamics of metformin were investigated in Korean healthy volunteers during a fasting state for over 10 h. In order to evaluate the amount of glucose-lowering effect of metformin, the plasma concentrations of glucose were measured for a period of 10 h followed by the administration of metformin (oral 500 mg) or placebo. In addition, the concentration of metformin in blood samples was determined by HPLC assay for the drug. All volunteers were consumed with 12 g of white sugar 10 minutes after drug intake to maintain initial plasma glucose concentration. The time courses of the plasma concentration of metformin and the glucose-lowering effect were analyzed by nonlinear regression analysis. The estimated $C_{max}$, $T_{max}$, $CL_{t}$/F (apparent clearance), V/F(apparent volume of distribution), and half-life of metformin were 1.42$\{pm}$0.07 $\mu\textrm{g}$/mL, 2.59$\{pm}$0.18h, 66.12$\{pm}$4.6 L/h, 26.63 L, and 1.54 h respectively. Since a significant counterclock-wise hysteresis was found for the metformin concentration in the plasma-effect relationship, indirect response model was used to evaluate pharmacodynamic parameters for metformin. The mean concentration at half-maximum inhibition $IC_{50}$, $k_{in}$, $k_{out}$ were 2.26 $\mu\textrm{g}$/mL, 83.26 $H^{-1}$, and 0.68 $H^{-1}$, respectively. Therefore, the pharmacokinetic-pharmacodynamic model may be useful in the description for the relationship between plasma concentration of metformin and its glucose-lowering effect.