• Title/Summary/Keyword: type 1 diabetes mellitus

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The Effects of Galgunhwanggumhwangryun-tang on Glucose and Energy Metabolism in C2C12 Myotubes (C2C12 골격근 세포에서 갈근황금황련탕의 당 대사 및 에너지 조절 효과)

  • Jihong Oh;Song-Yi Han;Soo Kyoung Lim;Hojun Kim
    • Journal of Korean Medicine for Obesity Research
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    • v.22 no.2
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    • pp.93-101
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    • 2022
  • Objectives: This study aimed to observe the anti-diabetic effect and underlying mechanisms of Galgunhwanggumhwangryun-tang (GHH; Gegen-Qinlian-decoction) in the C2C12 myotubes. Methods: GHH (1.0 mg/ml) or metformin (0.75 mM) or insulin (100 nM) were treated in C2C12 myotubes after 4 days differentiation. The glucose uptake was assessed by 2-[N-(7-160 nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake by C2C12 cells. The expression of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation AMPK (pAMPK) were measured by western blot. We also evaluated gene expression of glucose transporter type 4 (Slc2a4, formerly known as GLUT4), glucokinase (Gk), carnitine palmitoyltransferase IA (Cpt1a), nuclear respiratory factors 1 (Nrf1), mitochondrial transcription factor A (Tfam), and peroxisome proliferator-activated receptor γ coactivator 1α (Ppargc1a) by quantitative real-time polymerase chain reaction. Results: GHH promoted glucose uptake in C2C12 myotubes. The expression of AMPK protein, which plays an essential role in glucose metabolism, was increased by treatment with GHH. GHH treatment tended to increase gene expression of Slc2a4, Gk, and Nrf1 but was not statistically significant. However, GHH significantly improved Tfam and Ppargc1a gene expression in C2C12 myotubes. Conclusions: In summary, GHH treatment promoted glucose uptake in C2C12 myotubes. We suggest that these effects are associated with increased gene expression involved in mitochondrial biosynthesis and oxidative phosphorylation, such as Tfam and Ppargc1a, and increased expression of AMPK protein.

The association of PBX1 polymorphisms with overweight/obesity and metabolic alterations in the Korean population

  • Ban, Ju-Yeon;Kang, Soon-Ah;Jung, Kyung-Hee;Kim, Hak-Jae;Uhm, Yoon-Kyung;Kim, Su-Kang;Yim, Sung-Vin;Choe, Bong-Keun;Hong, Seung-Jae;Seong, Yeon-Hee;Koh, In-Song;Chung, Joo-Ho
    • Nutrition Research and Practice
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    • v.2 no.4
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    • pp.289-294
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    • 2008
  • Pre-B-cell leukemia transcription factor 1 (PBX1), which is located on chromosome 1q23, was recently reported to be associated with type 2 diabetes mellitus. We examined whether single nucleotide polymorphisms (SNPs) of the PBX1 gene are associated with overweight/obesity in a Korean population. We genotyped 66 SNPs in the PBX1 gene and investigated their association with clinical phenotypes found in 214 overweight/obese subjects and 160 control subjects using the Affymetrix Targeted Genotyping chip array. Seven SNPs (g.+75l86C>T, g.+78350C>A, g.+80646C>T, g.+138004C>T, g.+185219G>A, g.+191272A>C, and g.+265317T>A) were associated with the risk of obesity in three models (codominant, dominant, and recessive) (P=0.007-0.05). Haplotype 1 (CAC) and 3 (TAC) of block 3 and haplotype 2 (GGAAT) of block 10 were also strongly associated with the risk of obesity. In the control group, subjects that had homozygote for the major allele for both g.+185219G>A and g.+191272A>C showed lower high density lipoprotein-cholesterol (HDL-C) level compared to those possessing the minor allele, suggesting that the association between the homozygote for the major allele for both g.+185219G>A and g.+191272A>C and HDL-C is attributable to the increased risk of obesity. This study suggests that the PBX1 gene is a possible risk factor in overweight/obese patients.

Growth and Antioxidant Activity of Gynura procumbens by Natural Media Composition in Hydroponic Cultivation Using Organic Nutrient Solution (유기 수경재배 시 천연배지 조성에 의한 명월초 생육 및 항산화 활성)

  • Lee, Kyu-Hoi;Lee, Sung-Hee;Kim, Ju Hyoung;Park, Jae-Ho
    • Korean Journal of Organic Agriculture
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    • v.27 no.3
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    • pp.341-351
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    • 2019
  • Gynura procumbens (Family Asteraceae) is a medicinal plant commonly found in tropical Asia countries such as China, Thailand, Indonesia, Malaysia, and Vietnam. Traditionally, it is widely used in many different countries for the treatment of a wide variety of health ailments such as kidney discomfort, rheumatism, diabetes mellitus, constipation, and hypertension. The objective of this study was to select the natural growth media for hydroponic cultivation of Gynura procumbens. The commercially available thirty four different organic nutrient solutions were analyzed for growing Gynura procumbens. After analysis, two organic nutrient solution were selected, mixed (pH 5.5~6.5 / EC 0.5~1.0 ds/m) and then used as organic fertilizers. Thirty day old seedlings were planted and the environmental conditions of the rhizosphere were also examined to select the natural media composition. The minimum temperature of rhizosphere by type of natural media was highest in cocopeat media and lowest in perlite media. Furthermore, plant growth was examined from 50 days old seedlings, and vermiculite was observed to be most effective and perlite was the least effective component as natural media. The total polyphenol content of the studied plant material was also higher in vermiculite in comparison to other growth media. The Gynura procumbens yields were also higher in vermiculite in comparison to other growth media. Thus, vermiculite can be used to improve Gynura procumbens plant growth as a natural growth media.

Pharmacophore Mapping and Virtual Screening for SIRT1 Activators

  • Sakkiah, Sugunadevi;Krishnamoorthy, Navaneethakrishnan;Gajendrarao, Poornima;Thangapandian, Sundarapandian;Lee, Yun-O;Kim, Song-Mi;Suh, Jung-Keun;Kim, Hyong-Ha;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.30 no.5
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    • pp.1152-1156
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    • 2009
  • Silent information regulator 2 (Sir2) or sirtuins are NAD(+)-dependent deacetylases, which hydrolyze the acetyllysine residues. In mammals, sirtuins are classified into seven different classes (SIRT1-7). SIRT1 was reported to be involved in age related disorders like obesity, metabolic syndrome, type II diabetes mellitus and Parkinson’s disease. Activation of SIRT1 is one of the promising approaches to treat these age related diseases. In this study, we have used HipHop module of CATALYST to identify a series of pharmacophore models to screen SIRT1 enhancing molecules. Three molecules from Sirtris Pharmaceuticals were selected as training set and 607 sirtuin activator molecules were used as test set. Five different hypotheses were developed and then validated using the training set and the test set. The results showed that the best pharmacophore model has four features, ring aromatic, positive ionization and two hydrogen-bond acceptors. The best hypothesis from our study, Hypo2, screened high number of active molecules from the test set. Thus, we suggest that this four feature pharmacophore model could be helpful to screen novel SIRT1 activator molecules. Hypo2-virtual screening against Maybridge database reveals seven molecules, which contains all the critical features. Moreover, two new scaffolds were identified from this study. These scaffolds may be a potent lead for the SIRT1 activation.

Dietary Exposure to Transgenic Rice Expressing the Spider Silk Protein Fibroin Reduces Blood Glucose Levels in Diabetic Mice: The Potential Role of Insulin Receptor Substrate-1 Phosphorylation in Adipocytes

  • Park, Ji-Eun;Jeong, Yeon Jae;Park, Joon Beom;Kim, Hye Young;Yoo, Young Hyun;Lee, Kwang Sik;Yang, Won Tae;Kim, Doh Hoon;Kim, Jong-Min
    • Development and Reproduction
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    • v.23 no.3
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    • pp.223-229
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    • 2019
  • Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR). T2DM is correlated with obesity and most T2DM medications have been developed for enhancing insulin sensitivity. Silk protein fibroin (SPF) from spiders has been suggested as an attractive biomaterial for medical purposes. We generated transgenic rice (TR) expressing SPF and fed it to diabetic $BKS.Cg-m+/+Lepr^{db}$ mice to monitor the changes in blood glucose levels and adipose tissue proteins associated with energy metabolism and insulin signaling. In the present study, the adipocyte size in abdominal fat in TR-SPF-fed mice was remarkably smaller than that of the control. Whereas the adenosine monophosphate-activated protein kinase (AMPK)-activated protein kinase and insulin receptor substrate 1 (IRS1) protein levels were increased in abdominal adipose tissues after TR-SPF feeding, levels of six-transmembrane protein of prostate 2 (STAMP2) proteins decreased. Phosphorylation of AMPK at threonine 172 and IRS1 at serine 307 and tyrosine 632 were both increased in adipose tissues from TR-SPF-fed mice. Increased expression and phosphorylation of IRS1 at both serine 307 and tyrosine 632 in adipose tissues indicated that adipocytes obtained from abdominal fat in TR-SPF-fed mice were more susceptible to insulin signaling than that of the control. STAMP2 protein levels decreased in adipose tissues from TR-SPF-fed mice, indicating that STAMP2 proteins were reducing adipocytes that were undergoing lipolysis. Taken together, this study showed that TR-SPF was effective in reducing blood glucose levels in diabetic mice and that concurrent lipolysis in abdominal adipocytes was associated with alterations of AMPK, IRS1, and STAMP2. Increased IRS1 expression and its phosphorylation by TR-SFP were considered to be particularly important in the induction of lipolysis in adipocytes, as well as in reducing blood glucose levels in this animal model.

Interrelationship of Matrix Metalloproteinase and $TNF-{\alpha}$ in Human Gingiva with Chronic Periodontitis associated to Type 2 Diabetes Mellitus (단순 만성 치주염 환자 및 2형 당뇨병을 가진 만성 치주염 환자의 치은조직에서 Matrix Metalloproteinase와 $TNF-{\alpha}$ 의 발현 양상 비교)

  • Kim, Doe-Heun;Park, Eei-Kyun;Shin, Hong-In;Cho, Je-Yeol;Suh, Jo-Young;Lee, Jae-Mok
    • Journal of Periodontal and Implant Science
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    • v.36 no.2
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    • pp.409-425
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    • 2006
  • 치주질환의 병원균은 세포벽의 항원에 의하여 조직내 존재하는 mononuclear phagocytes가 활성화되어 cytokine들이 생성됨 으로써 치주 결체조직의 파괴를 진행시킨다. 이런 관련된 cytokine들은 순차적으로 상주하는 치은세포 및 대식세포가 Matrix metalloproteinase 합성을 하도록 유도하여 조직파괴를 시작한다. 이들 Matrix metalloproteinase중 MMP-2, MMP-9 (Gelatinase A,B)는 type IV collagen 및 변성된 interstitial collagen을 파괴하며 치주환자의 치은 열구액, 치은조직, 타액 네에서 높게 보고 되어왔다. 당뇨병은 치주질환의 위험요소중 하나로 달뇨 환자에서는 치주질환의 유병율이 일반인에 비해 높고 치주질환의 중증도도 더 심하여 진행도 빠르다고 알려져 있다. 그 병리 기전 중 하나로는 당뇨 환자에서는 치은 열구액 내 중성구 유래의 Matrix metalloproteinase의 활성 증가 및$TNF-{\alpha}$ 의 활성 증가가 추정되고 있다. 본 실험에서는 제2형 당뇨병 환자와 비당뇨 환자들에서 만성 치주염 부위의 치은 및 건강한 치은에서 염증매개체 중 하나인 MMP-2, MMP-9 및 $TNF-{\alpha}$ 의 발현에 대해 상호 비교 분석함으로서 염증, 혈당이 미치는 영향을 밝히고 제 2형 당뇨병 환자에서 심한 치주조직 파괴의 기전을 연구하고자 하였다. 경북대학교병원 치주과 내원환자 중 제2형 당뇨병 환자와 비당뇨 환자들 및 치주질환이 없는 건강인 대조군을 대상으로 여러 가지 환자요소, 임상 치주상태를 기록하고, 전신적으로 건강한 환자의 건강한 부위(n=8,Group 1), 전신적으로 건강한 환자으 만성 치주염 부위(n=8, Group 2), 제2형 당뇨병 환자의 만성 치주염 부위 (n=8,Group 3)에서 각각 변연치은을 채득하고 액화질소에 급속 동결하였다. Western blotting을 이용하여 각 조직 내 MMP-2, MMP-9 및 $TNF-{\alpha}$ 의 발현을 관찰, densitometer를 이용하여 상대적 발현을 정량, 각 조직의${\beta}-actin$을 이용하여 표준화하여 실험군과 대조군들의 평균치를 비교하였다. 비당뇨 환자들의 만성 치주염 부위 및 제2형 당뇨병 환자의 만성 치주염 부위에서 모두 건강 대조군에 비해 MMP-2와 MMP-9 의 발현이 증가되었다. 또한 MMP-2와 MMP-9는 2형 당뇨 환자의 만성 치주염 부위가 비당뇨 환자의 만성 치주염 부위보다 증가된 발현양상을 보였으며, $TNF-{\alpha}$ 발현 비교시 각 군간 유의성 있는 변화는 없었으나 2형 당뇨환자군에서 MMP-2 및 MMP-9의 증가와 함께 다소 증가 양상을 보였다. 결론적으로 본 실험에서 MMP-2 및 MMP-9의 증가가 만성 치주염 및 2형 당뇨 환자에서의 만성치주염에서 비당뇨환자 보다 MMP-2, MMP-9의 증가양상을 보여 주었으며 $TNF-{\alpha}$ 가 2형 당뇨환자의 만성치주염 진행과정에 기여인자로써 역할을 하는 것으로 생각된다.

Antiproliferative Effect of Opuntia humifusa Ethanol Extract on Human Carcinoma HT-29 Cells (천년초 선인장 줄기 에탄올 추출물의 HT-29 대장암 세포증식 저해효과)

  • Park, Soo Young;Kim, Young A;Ly, Sun Yung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.12
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    • pp.1827-1834
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    • 2014
  • Colon cancer is the third highest cause of death in Korea. Known dietary causes of colon cancer include a diet rich in fat and red meat as well as inadequate intake of dietary fiber, fruits, and vegetables. Therefore, recent research has focused on the anticancer effects of natural products. Opuntia humifusa is a type of prickly pear that is known to contain biologically active compounds that can be used in the treatment of diabetes mellitus, arteriosclerosis, and hyperglycemia. The aim of this study was to determine whether or not O. humifusa extract affects proliferation, cell death, and DNA fragmentation in human carcinoma HT-29 cells. O. humifusa is rich in carbohydrates, minerals (Mg, K, and Ca), and total phenolics. HT-29 cells were treated with extracts of O. humifusa at concentrations of 0, 0.25, 0.5, 1, and 2 mg/mL for 24 or 48 hours. O. humifusa extracts inhibited HT-29 cell growth in a dose-dependent manner. Hoechst 33342/PI double staining and Comet assay were performed to observe changes in nuclei of cancer cells undergoing cell death. The results of both tests showed that O. humifusa extract induced cell shrinkage, DNA fragmentation, and chromatin condensation dose-dependently in HT-29 cells. The results of this study suggest that O. humifusa extract inhibits the growth of HT-29 via induction of DNA fragmentation and chromatin condensation.

Risk Factors and Preoperative Risk Scoring System for Shunt-Dependent Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage

  • Kim, Joo Hyun;Kim, Jae Hoon;Kang, Hee In;Kim, Deok Ryeong;Moon, Byung Gwan;Kim, Joo Seung
    • Journal of Korean Neurosurgical Society
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    • v.62 no.6
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    • pp.643-648
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    • 2019
  • Objective : Shunt-dependent hydrocephalus (SdHCP) is a well-known complication of aneurysmal subarachnoid hemorrhage (SAH). The risk factors for SdHCP have been widely investigated, but few risk scoring systems have been established to predict SdHCP. This study was performed to investigate the risk factors for SdHCP and devise a risk scoring system for use before aneurysm obliteration. Methods : We reviewed the data of 301 consecutive patients who underwent aneurysm obliteration following SAH from September 2007 to December 2016. The exclusion criteria for this study were previous aneurysm obliteration, previous major cerebral infarction, the presence of a cavum septum pellucidum, a midline shift of >10 mm on initial computed tomography (CT), and in-hospital mortality. We finally recruited 254 patients and analyzed the following data according to the presence or absence of SdHCP : age, sex, history of hypertension and diabetes mellitus, Hunt-Hess grade, Fisher grade, aneurysm size and location, type of treatment, bicaudate index on initial CT, intraventricular hemorrhage, cerebrospinal fluid drainage, vasospasm, and modified Rankin scale score at discharge. Results : In the multivariate analysis, acute HCP (bicaudate index of ${\geq}0.2$) (odds ratio [OR], 6.749; 95% confidence interval [CI], 2.843-16.021; p=0.000), Fisher grade of 4 (OR, 4.108; 95% CI, 1.044-16.169; p=0.043), and an age of ${\geq}50years$ (OR, 3.938; 95% CI, 1.375-11.275; p=0.011) were significantly associated with the occurrence of SdHCP. The risk scoring system using above parameters of acute HCP, Fisher grade, and age (AFA score) assigned 1 point to each (total score of 0-3 points). SdHCP occurred in 4.3% of patients with a score of 0, 8.5% with a score of 1, 25.5% with a score of 2, and 61.7% with a score of 3 (p=0.000). In the receiver operating characteristic curve analysis, the area under the curve (AUC) for the risk scoring system was 0.820 (p=0.080; 95% CI, 0.750-0.890). In the internal validation of the risk scoring system, the score reliably predicted SdHCP (AUC, 0.895; p=0.000; 95% CI, 0.847-0.943). Conclusion : Our results suggest that the herein-described AFA score is a useful tool for predicting SdHCP before aneurysm obliteration. Prospective validation is needed.

Treatment outcomes of neoadjuvant concurrent chemoradiotherapy followed by esophagectomy for patients with esophageal cancer

  • Kim, Yong-Hyub;Song, Sang-Yun;Shim, Hyun-Jeong;Chung, Woong-Ki;Ahn, Sung-Ja;Yoon, Mee Sun;Jeong, Jae-Uk;Song, Ju-Young;Nam, Taek-Keun
    • Radiation Oncology Journal
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    • v.33 no.1
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    • pp.12-20
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    • 2015
  • Purpose: To evaluate treatment outcomes and determine prognostic factors in patients with esophageal cancer treated with esophagectomy after neoadjuvant chemoradiotherapy (NCRT) Materials and Methods: We retrospectively evaluated 39 patients with esophageal cancer who underwent concurrent chemoradiotherapy followed by esophagectomy between 2002 and 2012. Initial clinical stages of patients were stage IB in 1 patient (2.6%), stage II in 5 patients (12.9%), and stage III in 33 patients (84.6%). Results: The median age of all the patients was 62 years, and the median follow-up period was 17 months. The 3-year overall survival (OS) rate was 33.6% in all the patients. The 3-year locoregional recurrence-free survival (LRFS) rate was 33.7%. In multivariate analysis with covariates of age, the Eastern Cooperative Oncology Group performance status, hypertension, diabetes mellitus, tumor length, clinical response, clinical stage, pathological response, pathological stage, lymphovascular invasion, surgical type, and radiotherapy to surgery interval, only pathological stage was an independent significant prognostic factor affecting both OS and LRFS. The complications in postoperative day 90 were pneumonia in 9 patients, anastomotic site leakage in 3 patients, and anastomotic site stricture in 2 patients. Postoperative 30-day mortality rate was 10.3% (4/39); the cause of death among these 4 patients was respiratory failure in 3 patients and myocardial infarction in one patient. Conclusion: Only pathological stage was an independent prognostic factor for both OS and LRFS in patients with esophageal cancer treated with esophagectomy after NCRT. We could confirm the significant role of NCRT in downstaging the initial tumor bulk and thus resulting in better survival of patients who gained earlier pathological stage after NCRT.

Convergence Analysis of Risk factors for Readmission in Cardiovascular Disease: A Machine Learning Approach (의사결정나무분석을 이용한 심혈관질환자의 재입원 위험 요인에 대한 융합적 분석)

  • Kim, Hyun-Su
    • Journal of Convergence for Information Technology
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    • v.9 no.12
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    • pp.115-123
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    • 2019
  • This is descriptive study to 2nd analysis data KNHANES IV-VI about risk factors of readmission among patients with cardiovascular disease. Among the total 65,973 adults, 1,037 with angina or myocardial infarction were analyzed. The analysis was conducted using SPSS window 21 Program and CHAID decision tree was used in the classification analysis. Root nodes are economic activity(χ2=12.063, p=.001), children's nodes are personal income(χ2=6.575, p=.031), weight change(χ2=12.758, p=.001), residential area(χ2=4.025, p=.045), direct smoking(χ2=3.884, p=.031). p=.049), level of education(χ2=9.630, p=.024). Terminal nodes are hypertension(χ2=3.854, p=.050), diabetes mellitus(χ2=6.056, p=.014), occupation type(χ2=7.799, p=.037). We suggest that the development and operation of programs considering the integrated approach of various factors is necessary for the readmission management of cardiovascular patients.