• Molecules and Cells
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• 제38권5호
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• pp.452-456
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• 2015

Obesity is the fifth leading risk for death globally, and a significant challenge to global health. It is a common, complex, non-malignant disease and develops due to interactions between the genes and the environment. DNA methylation can act as a downstream effector of environmental signals; analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. To assess the effects of excessive weight and obesity on gene-specific methylation levels of promoter regions, we determined the methylation status of four genes involved in inflammation and oxidative stress [interleukin 6 (IL6), tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$), mitochondrial transcription factor A (TFAM), and glucose transport 4 (GLUT4)] in blood cell-derived DNA from healthy women volunteers with a range of body mass indices (BMIs) by methylation-specific PCR. Interestingly, the samples from obese individuals ($BMI{\geq}30kg/m^2$) showed significantly increased hypermethylation for IL6 gene compared to normal weight ($BMI<23kg/m^2$) and overweight sample ($23kg/m^2{\leq}BMI<30kg/m^2$) (P = 0.034 and P = 0.026). However there was no statistically significant difference in promoter methylation of the other 3 genes between each group. These findings suggest that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment. Further studies are required to elucidate the potential mechanisms underlying this relationship.

• 대한본초학회지
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• 제32권5호
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• pp.39-46
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• 2017

Objective : This study was designed to evaluate the hypoglycemic effects of Helianthus tuberosi Rhizoma extracts and its optimum Heat processing conditions Methods : We investigated the Salivary ${\alpha}$-amylase, pancreas ${\alpha}$-amylase and ${\alpha}$-glucosidase inhibitory activities of extracts from Steam Heated Helianthus tuberosi Rhizoma Ext. The inhibitory activities of a 50% EtOH extract of Steam Heated Helianthus tuberosi Rhizoma Ext against ${\alpha}$-glucosidases were evaluated in this study. Inhibiting these enzymes involved in the absorption of disaccharides significantly decreases the postprandial increase in blood glucose level after a mixed carbohydrate diet. Furthermore, the postprandial blood glucose lowering effect of Steam Heated Helianthus tuberosi Rhizoma Ext. was compared to a known type 2 diabetes drug(Acarbose(R)) in a mice model. Steam Heated Helianthus tuberosus L. Ext significantly reduced the blood glucose increase after glucose loading. Results : The results were confirmed by real-time PCR that after treated with Streptozotocin in L6 cells, induced expression of GLUT4, after the steamed Helianthus tuberosus L. Ext. treated, observed its expression was increased. Steam Heated Helianthus tuberosus L Ext treated 4 hours in L6 cells, cytotoxicity was measured in MTT assay. Its toxicity were 5.7%, 9% and 11.3% at the treatment concentration $12.5{\mu}g/m{\ell}$, $25{\mu}g/m{\ell}$, the $50{\mu}g/m{\ell}$ respectively. Conclusions : Overall, the results of this study indicate that Hypoglycemic effect of Helianthus tuberosi Rhizoma caused by the Steam heat treatment, the optimum Heat processing condition is steamming at $121^{\circ}C$ for 30 min, and it will provide the basis for developing a useful dietary supplement for controlling postprandial hyperglycemia.

• 운동영양학회지
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• 제16권2호
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• pp.85-92
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• 2012

This study was conducted to examine the possibility of Salicornia herbacea L. powder as a functional food beneficially affecting carbohydrate metabolism and antioxidant capacity. Twenty-four, 6-week old, maleSprague-Dawleyrats were classified into three groups: normal diet control (CON), high-fat diet control (HFC) and high fat diet + Salicornia herbacea L. (SHF). Related feed was provided to each group for 4 weeks. Weight gain rate increased most in the HFC rats, and the concentration of glucose was significantly high in both the HFC and SHF groups, compared to the CON group. The SHF group showed a significantly high expression rate of Glut 4 (21.36%), compared to the CON and HFC groups. The glycogen content in muscle was significantly high in both the HFC and SHF groups, compared to the CON group. There were significant differences in the malondialdehydecontent in muscles between the groups, with the content in the CON and HFC groups being significantly higher than the SHF group. All the groups showed a similar tendency to each other in the liver tissue as well. Concerning the expression of Cu,Zn-super oxide dismutase andglutathione peroxidaseproteins, the SHF group was significantly higher than the CON and HFC groups. Overall, the experiment result above implies a possibility that an intake of Salicornia herbacea L. powder can regulate weight by decreasing the weight gain rate, further suggesting its effectiveness as a functional food before exercise by increasing the energy storage capacity and antioxidant capacity.

• 한국산학기술학회논문지
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• 제15권6호
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• pp.3799-3804
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• 2014

Mycosporine-like 아미노산(MAAs)은 UV 흡수물질이며, 다양한 해양생물들은 MAAs의 합성과 축적을 통하여 환경자외선의 직 간접적인 영향을 감소시키는 기능을 진화시켜 왔다. 이 연구에서는 미세조류, Chlamydomonas hedleyi에 포도당 전달 단백질인 Glucose transporter 1(Glut-1) 유전자를 pCAM1303 벡터에 도입한 형질전환체를 제작하여, 형질전환체의 바이오매스를 최대로 증가시킬 수 있는 최적의 Glucose 농도와 NH4Cl농도를 결정하고, 고주파(Radiofrequency) 발생장치를 활용한 바이오매스 증가와 함께 MAA를 대량 생산할 수 있는 배양 조건을 확립하였다. 연구결과 고주파 처리를 통한 형질전환 미세조류는 4.13 mg/L(MAAs/DCW)으로 3.23 mg/L(MAAs/DCW)의 고주파 처리 없이 배양한 형질전환체보다 효율이 증가하였다. 이러한 결과는 자외선 A 흡수물질을 인위적으로 증폭시킬 수 있어서, 대량배양한 후 MAAs물질을 분리 및 정제하여 피부자극성이 없는 친환경적인 자외선 차단 화장품 산업화에 크게 기여할 수 있음을 의미한다.

• Genomics & Informatics
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• 제12권4호
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• pp.240-246
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• 2014

Mutation in HNF1B, the hepatocyte nuclear factor-$1{\beta}$ (HNF-$1{\beta}$) gene, results in maturity-onset diabetes of the young (MODY) 5, which is characterized by gradual impairment of insulin secretion. However, the functional role of HNF-$1{\beta}$ in insulin secretion and glucose metabolism is not fully understood. We identified a family with early-onset diabetes that fulfilled the criteria of MODY. Sanger sequencing revealed that a heterozygous P159L (CCT to CTT in codon 159 in the DNA-binding domain) mutation in HNF1B was segregated according to the affected status. To investigate the functional consequences of this HNF1B mutation, we generated a P159L HNF1B construct. The wild-type and mutant HNF1B constructs were transfected into COS-7 cells in the presence of the promoter sequence of human glucose transporter type 2 (GLUT2). The luciferase reporter assay revealed that P159L HNF1B had decreased transcriptional activity compared to wild-type (p < 0.05). Electrophoretic mobility shift assay showed reduced DNA binding activity of P159L HNF1B. In the MIN6 pancreatic ${\beta}$-cell line, overexpression of the P159L mutant was significantly associated with decreased mRNA levels of GLUT2 compared to wild-type (p < 0.05). However, INS expression was not different between the wild-type and mutant HNF1B constructs. These findings suggests that the impaired insulin secretion in this family with the P159L HNF1B mutation may be related to altered GLUT2 expression in ${\beta}$-cells rather than decreased insulin gene expression. In conclusion, we have identified a Korean family with an HNF1B mutation and characterized its effect on the pathogenesis of diabetes.

• 생명과학회지
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• 제29권5호
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• pp.570-579
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• 2019

당뇨병은 서구화된 식습관으로 발생하는 심각한 만성대사질환의 하나이며, 당뇨병의 치료는 혈당을 정상적인 수준으로 유지하며 당뇨 합병증을 예방하는 것이다. 따라서 본 연구는 당뇨병 및 인슐린 저항성에 대한 유전적 분석에 널리 이용되는 C57BL/Ksj-db/db 당뇨동물모델을 이용하여 갈색거저리 유충(밀웜) 추출물의 6주간 섭취가 혈당개선에 미치는 영향에 대해 조사하고 이에 인슐린 민감성 개선과 당대사 조절을 통한 항당뇨 효과를 규명하고자 하였다. 제 2형 당뇨동물모델 실험 결과, db/db-MWE군(식이 0.5%)이 db/db-control군에 비해 유의적(p<0.05)으로 혈당이 감소하였다. 약물군인 db/db-RG군(식이 0.05%)은 부작용에 의해 눈에 띄게 체중이 증가하였으나, db/db-MWE군에서는 약물군에서의 체중증가와 같은 큰 부작용 없이 혈당 감소효과를 나타내었다. HbA1c와 혈장인슐린 농도의 경우 db/db-control군에 비해 db/db-MWE군이 유의적(p<0.05)으로 낮았다. 또한 골격근에서 p-IRS, p-AKT, PM-GLUT4의 발현을 확인한 결과, db/db-MWE군에서 db/db-control군에 비해 p-IRS, p-AKT, PM-GLUT4의 발현이 증가된 것을 알 수 있었다. 이는 밀웜 추출물의 섭취가 골격근 내로 당이 원활이 유입되도록 도와주어 인슐린 민감성을 개선시키며, 고혈당 증상을 개선시킨 것으로 사료된다. 밀웜 추출물을 식이에 0.5% 첨가하여 6주간 C57BL/Ksj-db/db 당뇨동물모델에 제공한 결과, 공복혈당과 HbA1c의 감소 및 인슐린 저항성을 개선시켰다. 이는 인슐린 민감성을 증가시키고, 당 대사 조절을 통해 고혈당 증상의 완화에 기인한 것으로 보인다. 따라서 밀웜은 당뇨병의 예방과 치료에 유용한 소재가 될 것으로 기대되며, 향후 제 2형 당뇨병 개선을 위해 더욱 다양한 연구가 이루어져야 할 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제20권6호
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• pp.581-593
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• 2016

The advantages of monounsaturated fatty acids (MUFAs) on insulin resistance and type 2 diabetes mellitus (T2DM) have been well established. However, the molecular mechanisms of the anti-diabetic action of MUFAs remain unclear. This study examined the anti-hyperglycemic effect and explored the molecular mechanisms involved in the actions of fish oil- rich in MUFAs that had been acquired from hybrid catfish (Pangasius larnaudii${\times}$Pangasianodon hypophthalmus) among experimental type 2 diabetic rats. Diabetic rats that were fed with fish oil (500 and 1,000 mg/kg BW) for 12 weeks significantly reduced the fasting plasma glucose levels without increasing the plasma insulin levels. The diminishing levels of plasma lipids and the muscle triglyceride accumulation as well as the plasma leptin levels were identified in T2DM rats, which had been administrated with fish oil. Notably, the plasma adiponectin levels increased among these rats. The fish oil supplementation also improved glucose tolerance, insulin sensitivity and pancreatic histological changes. Moreover, the supplementation of fish oil improved insulin signaling ($p-Akt^{Ser473}$ and p-PKC-${\zeta}/{\lambda}^{Thr410/403}$), $p-AMPK^{Thr172}$ and membrane GLUT4 protein expressions, whereas the protein expressions of pro-inflammatory cytokines (TNF-${\alpha}$ and nuclear NF-${\kappa}B$) as well as p-PKC-${\theta}^{Thr538}$ were down regulated in the skeletal muscle. These data indicate that the effects of fish oil-rich in MUFAs in these T2DM rats were partly due to the attenuation of insulin resistance and an improvement in the adipokine imbalance. The mechanisms of the anti-hyperglycemic effect are involved in the improvement of insulin signaling, AMPK activation, GLUT4 translocation and suppression of pro-inflammatory cytokine protein expressions.

• 한국식품과학회지
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• 제52권1호
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• pp.81-88
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• 2020

PGSE의 혈당조절 효과를 평가하기 위하여 제2형 당뇨 동물모델을 이용하여 8주간의 동물실험을 진행한 결과, 고농도 PGSE(600 mg/kg)의 투여는 경구 포도당 내성 및 혈당 수준을 유의적으로 감소시켰으며(p<0.05), 당화혈색소도 유의적으로 낮은 수준을 유지시켰다(p<0.05). 또한, 혈청 인슐린과 렙틴 농도 역시 대조군과 비교하여 PGSE 고농도 처리군에서 유의적으로 감소하였다(p<0.05). PGSE 투여는 db/db 마우스의 골격근에서 인슐린 의존적 세포신호전달경로를 유의적으로 활성화시켰으며, AMPK 인산화를 촉진시키고, 골격근내 포도당 흡수를 위한 GLUT4의 세포막으로의 전이를 대조군 대비 약 1.7배 증가시켰다. 이러한 결과를 근거로 할 때 PGSE는 항 당뇨병 치료제로서의 잠재적 가능성을 가진 것으로 판단된다.

• Fisheries and Aquatic Sciences
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• 제23권9호
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• pp.24.1-24.9
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• 2020

Brown alga (Ishige okamurae; IO) dietary supplements have been reported to possess anti-diabetic properties. However, the effects of IO supplements have not been evaluated on glucose metabolism in the pancreas and skeletal muscle. C57BL/6 N male mice (age, 7 weeks) were arranged in five groups: a chow diet with 0.9% saline (NFD/saline group), high-fat diet (HFD) with 0.9% saline (HFD/saline group). high-fat diet with 25 mg/kg IO extract (HFD/25/IOE). high-fat diet with 50 mg/kg IO extract (HFD/50/IOE), and high-fat diet with 75 mg/kg IO extract (HFD/75/IOE). After 4 weeks, the plasma, pancreas, and skeletal muscle samples were collected for biochemical analyses. IOE significantly ameliorated glucose tolerance impairment and fasting and 2 h blood glucose level in HFD mice. IOE also stimulated the protein expressions of the glucose transporters (GLUTs) including GLUT2 and GLUT4 and those of their related transcription factors in the pancreases and skeletal muscles of HFD mice, enhanced glucose metabolism, and regulated blood glucose level. Our results suggest Ishige okamurae extract may reduce blood glucose levels by improving glucose metabolism in the pancreas and skeletal muscle in HFD-induced diabetes.

• 동의생리병리학회지
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• 제17권2호
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• pp.529-541
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• 2003

Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.