• Environmental Analysis Health and Toxicology
• /
• 제19권3호
• /
• pp.287-294
• /
• 2004

Diabetic complication is one of major risk factors leading to vascular disease such as atherosclerosis, stroke, coronary heart disease and etc. Several factors affecting the acceleration of diabetic vascular complication have been known such as hypertension, hyperlipidemia, immune complex and genetic factors. To screen and develop new therapeutics agents for diabetic vascular complication, it is strongly needed to develop animal models for diabetic complications. However in rodents models, diabetic complications is not well developed. Furthermore to assess the possibility of new therapeutics for diabetic vascular complications, diabetic animal models which have the risk factors of diabetic complications is needed. We aim to develop and establish an diabetic animal model which have diabetic complications with hyperlipidemia which is one of risk factors for diabetic complications. We induced insulin -dependent diabetes by intra. venous injection of streptozotocin (35 mg/kg/day) in RICO rats which is a spontaneous animal model for hyperlipidemia. Our models (STZ RICO) showed hyperglycemia, persistent high level of plasma cholesterol and triglyceridemia with severe diabetic renal changes until 28 weeks after induction of diabetes. STZ-RICO rats could be used for the evaluations of newly developed diabetic drugs.

• Archives of Pharmacal Research
• /
• 제23권4호
• /
• pp.267-282
• /
• 2000

Cytochrome P45O (CYP) 2E1 catalyzes the metabolism of a wide variety of therapeutic agents, procarcinogens, and low molecular weight solvents. CYP2E1-catalyzed metabolism may cause toxicity or DNA damage through the production of toxic metabolites, oxygen radicals, and lipid peroxidation. CYP2E1 also plays a role in the metabolism of endogenous compounds including fatty acids and ketone bodies. The regulation of CYP2E1 expression is complex, and involves transcriptional, post-transcriptional, translational, and post-translational mechanisms. CYP2E1 is transcriptionally activated in the first few hours after birth. Xenobiotic inducers elevate CYP2E1 protein levels through both increased translational efficiency and stabilization of the protein from degradation, which appears to occur primarily through ubiquitination and proteasomal degradation. CYP2E1 mRNA and protein levels are altered in response to pathophysiologic conditions by hormones including insulin, glucagon, growth hormone, and leptin, and growth factors including epidermal growth factor and hepatocyte growth factor, providing evidence that CYP2E1 expression is under tight homeostatic control.

• Nutrition Research and Practice
• /
• 제14권6호
• /
• pp.580-592
• /
• 2020

BACKGROUND/OBJECTIVES: The present study aimed to further investigate the potential health beneficial effects of long-term seaweed supplementation on lipid metabolism and hepatic functions in DIO mice. MATERIALS/METHODS: Four brown seaweeds (Undaria pinnatifida [UP], Laminaria japonica [LJ], Sargassum fulvellum [SF], or Hizikia fusiforme [HF]) were added to a high fat diet (HFD) at a 5% ratio and supplemented to C57BL/6N mice for 16 weeks. Triglycerides (TGs) and total cholesterol (TC) in the liver, feces, and plasma were measured. Fecal bile acid (BA) levels in feces were monitored. Hepatic insulin signaling- and lipogenesis-related proteins were evaluated by Western blot analysis. RESULTS: Fasting blood glucose levels were significantly reduced in the LJ, SF, and HF groups compared to the HFD group by the end of 16-week feeding period. Plasma TG levels and hepatic lipid accumulation were significantly reduced in all 4 seaweed supplemented groups, whereas plasma TC levels were only suppressed in the UP and HF groups compared to the HFD group. Fecal BA levels were significantly elevated by UP, LJ, and SF supplementation compared to HFD feeding only. Lastly, regarding hepatic insulin signaling-related proteins, phosphorylation of 5'-AMP-activated protein kinase was significantly up-regulated by all 4 types of seaweed, whereas phosphorylation of protein kinase B was up-regulated only in the SF and HF groups. Lipogenesis-related proteins in the liver were effectively down-regulated by HF supplementation in DIO mice. CONCLUSIONS: Brown seaweed consumption showed hypotriglyceridemic effects in the prolonged DIO mouse model. Specifically, combinatory regulation of BA excretion and lipogenesis-related proteins in the liver by seaweed supplementation contributed to the reduction of plasma and hepatic TG levels, which inhibited hyperglycemia in DIO mice. Thus, the discrepant and species-specific functions of brown seaweeds provide novel insights for the selection of future targets for therapeutic agents.

• Journal of Nutrition and Health
• /
• 제51권3호
• /
• pp.201-207
• /
• 2018

본 연구에서는 고지방식이로 유도한 비만 C57BL/6N 마우스 모델에서 누에체액 투여가 마우스의 체중 감소 및 혈중 지질 개선 효과를 보이는지 평가하였다. 실험동물은 정상군 (N), 고지방대조군 (HFC), 누에체액투여군 (HFS-1, HFS-5, HFS-10)으로 분리하여 12주 동안 열량비 10% 지방식이나 45% 지방식을 섭취시키고 고지방식이 급여군들의 일부에 누에체액을 체중 대비 1%, 5%, 10% 경구투여 하였다. 그 결과 체중과 부고환지방 및 총지방의 무게가 유의하게 감소하였으며 혈장 LDL-cholesterol 농도가 고지방대조군 (HFC)군에 비하여 HFS-1, HFS-5, HFS-10군에서 유의하게 감소하였다. 혈중 ALT와 AST의 활성은 고지방대조군에 비하여 HFS-5, HFS-10 군에서 유의하게 저하되었고 누에체액을 투여한 모든 군에서 HFC군과 비교하여 혈장 leptin 수준이 유의하게 감소하였다. 비록 누에체액의 유효성분을 동정하고 그 특성을 규명하기 위해서는 더 많은 연구를 필요로 하지만 본 연구 결과는 누에체액이 비만을 예방할 수 있는 잠재적인 천연소재로서 가능성을 보여준다.

• 약학회지
• /
• 제58권1호
• /
• pp.71-79
• /
• 2014

Although Korean patients with type 2 diabetes mellitus (T2DM) are generally treated by western medicine, many of them strongly believe in the traditional oriental Sasang constitutional classification and depend on it for food, health supplements, and oriental medicines decision making. Sasang constitutional classification is a part of traditional Korean medicine that divides people into four constitutional types (Tae-Yang: TY, Tae-Eum: TE, So-Yang: SY, and So-Eum: SE), which differ in inherited characteristics such as appearance, personality traits, susceptibility to diseases, and drug responses. It is recommended for T2DM patients to control their blood glucose very well from early stages with drugs and diet. However, many T2DM patients respond differently to their drugs, even though they receive the same medicine. Therefore, the present study investigated whether Sasang constitutional type can explain the therapeutic differences between oral hypoglycemic agents (OHAs) therapy (mono, dual and triple drug therapy). Patients of 618 with T2DM diagnosis and Sasang constitutional type known who received both western and oriental medicine treatment in a hospital between April 2006 and April 2013 retrospectively studied. HbA1c (%) and blood glucose (mg/dl) levels before OHAs therapy and 3 month after were collected for metformin (MET) or sulfonylurea (SU) monotherapy, MET+SU dual therapy, MET+except SU (where was either alpha-glucosidase inhibitor, dipeptidyl peptidase-4 inhibitor, meglitinide or thiazolidinedione) dual therapy, and triple therapy, according to Sasang constitutional type. For statistical analysis, ANOVA was used and paired t-test by SPSS 19.0 where P values less than 0.05 were considered statistically significant. Pattern was similar levels of HbA1c and blood glucose and which was decreased in order of mono, MET+SU dual, MET+except SU dual and triple therapy. In all patients comparison, for the So-yang (SY) constitutional type, either monotherapy was less effective; for Te-eum (TE) type, MET+SU dual therapy was less effective while MET+except SU dual therapy was more effective and the triple therapy was less effective; and for So-eum (SE) type, the triple therapy was more effective. For the management of TE type it is recommended to use drugs except SU when dual therapy is needed, restrict triple therapy and consider dual and insulin therapy; for SY type it is recommended to follow current guidelines; and for SE type it is advisable to skip dual therapy and start the triple therapy early. Finally, the therapeutic response to OHAs is different among Korean T2DM patients with different Sasang constitutional types. Taken together, the choice of effective OHAs therapy for each type is necessary in order to minimize the poor control of blood glucose level, the risk of complications, and the costs from a failure of therapy.

• 성인간호학회지
• /
• 제24권4호
• /
• pp.406-416
• /
• 2012

Purpose: The purposes of this secondary data analysis study were first to identify the number of Korean adults achieving goals set by the American Diabetes Association for hemoglobin A1c (HbA1c), blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C), and secondly to identify the characteristics associated with lack of goals attainment. Methods: The sample was 413 Koreans with diagnosed diabetes aged thirty years or older who participated in the Fourth Korea National Health and Nutrition Examination Survey. Goals attainment for HbA1c, BP, and LDL-C were presented in percentages. Logistic regressions were used to examine associations between participants' characteristics and lack of goals attainment. Results: About 48% had HbA1c<7%, 48.2% had BP<130/80mmHg, and 34.1% had LDL-C<100mg/dL. Only 8.7% of the sample achieved all three parameters. In multivariate analysis, younger age, longer diabetes duration, insulin use, and abdominal obesity were associated with not meeting HbAlC goal. Smoking and use of antihypertensive medication were associated with BP${\geq}$130/80 mmHg. No use of lipid lowering agents was associated with LDL-C${\geq}$100 mg/dL. Conclusion: Many Koreans with diabetes were not at goals for HbA1c, BP, and LDL-C. For optimal control, appropriateness of therapy and poor lifestyle habits should be assessed periodically and managed accordingly.

• 동의생리병리학회지
• /
• 제34권2호
• /
• pp.75-80
• /
• 2020

In this study, we investigated the dose-dependent effects of mixtures of Atractylodes macrocephala (AM) and Amomum villosum (AV) water extracts in a ratio of 3:1 on high fat diet (HFD)-induced obesity model. Oral administration of various concentrations with mixtures of AM and AV extracts in a ratio of 3:1 for 6 weeks inhibited HFD-induced increases of body, liver and epididymal fat weights in a dose-dependent fashions. Those effects may be mediated by decreased expressions of lipogenesis-related genes such as acetyl coA carboxylase (ACC) and fatty acid synthase (FAS) in liver. Also, increase of insulin and decrease of adiponectin in serum by HFD supply were inhibited by three different dosages of mixtures of AM and AV extracts in a ratio of 3:1. HFD supply induced increases of serum total cholesterol, triglyceride and LDL cholesterol. However, hyperlipidemia was significantly decreased in dose-dependent manners by treatment with mixtures of AM and AV extracts. Based on the results of the present study, hypolipidemic and anti-obesity effects by mixtures of AM and AV extracts were found in HFD-induced obesity model. Further clinical investigation is needed to develop anti-obesity therapeutic or preventive agents by using mixtures of AM and AV extracts.

• 한방안이비인후피부과학회지
• /
• 제19권3호통권31호
• /
• pp.22-33
• /
• 2006

Objective : Angiogenesis induced by hypoxia and inflammation are an essential process of solid tumors and psoriasis. We researched the HIF-1 ${\alpha}$ (hypoxia inducible factor 1 alpha), VEGF(Vascular Endothelial Growth Factor), survival related PI3K-Akt, and inflammation related COX-2 protein expressions to get the information of the mechanism and effects of Rehmannia glutinosa in HepG2 and HaCaT cell lines. Method : To investigate the roles of the Rehmannia glutinosa extract, we performed MTS assay and western blots using HaCaT cells and HepG2 cells. HaCaT cells and HepG2 cells were treated with $50{\mu}g/ml$ and $100{\mu}g/ml$ Rehmannia glutinosa extracts. After 4hrs, HaCaT cells were treated with IGF-II protein for 24hrs and HepG2 cells were treated with $CoCl_2$. Results : 1. We could ohserve that the reduction of the protein level of HIT-1 ${\alpha}$ induced by IGF-II in HaCaT cells. 2. We Could ohserve that the decreased PI3K-Akt and COX-2 expression level by Rehmannia glutinosa extracts treated in HaCaT cells independently ith ERK1/2. 3. We could observe that the reduction of the protein level of HIF-1 ${\alpha}$ induced by $CoCl_2$ in HepG2 cells. Conclusion : These results suggest that Rehmannia glutinosa extracts contributes to the anti-survival pathway and anti-inflammatory activities. Also, we could assume that Rehmannia glutinosa act as anti-inflanmmatory or anti-hypoxia agents via reduction of COX-2 and HIF-1 ${\alpha}$.

• Journal of Yeungnam Medical Science
• /
• 제11권1호
• /
• pp.153-159
• /
• 1994

당뇨병을 가진 백내장 환자에 있어서 수정체낭외적출술 및 후방인공수정체삽입술후 당뇨망막증의 경과변화, 시력의 예후, 시력의 예후 및 망막증의 진행에 영향을 미치는 관련인자들에 대한 후향적 조사를 시행하여 다음과 같은 결과를 얻었다. 1. 백내장수술을 한 눈의 경우 전체 24안중 11안(46%)에서 망막증이 진행하였으며 수술을 하지 않은 눈의 경우 망막증의 진행을 보인 경우는 4안(17%)이였다. 2. 백내장수술후 시력이 향상되었던 경우는 24안 중 22안(92%)이였으나 이중 0.5이하가 12안, 0.1이하가 3안이였다. 3. 술후 망막증의 진행이 있었던 경우 여자는 11안 중 7안, 남자는 13안 중 4안이였으며 경구 혈당강하제를 사용하는 환자가 인슐린 투여군보다 망막증의 진행이 더욱 많았다. 4. 본 연구의 결과 백내장수술은 당뇨망막증의 진행을 더욱 촉진시키며 경구혈당강하제의 사용, 그리고 여자환자에서 망막증의 진행이 더욱 빈번히 나타났으며 이는 시력의 예후를 나쁘게 하는 인자로 작용하였다.

• 한방비만학회지
• /
• 제18권1호
• /
• pp.10-18
• /
• 2018

Objectives: Metabolic syndrome is correlated with increased cardiovascular risk and characterized by several factors, including visceral obesity, hypertension, insulin resistance, and dyslipidemia. Several members of a large family of nonselective cation entry channels, e.g., transient receptor potential (TRP) melastatin 7 (TRPM7) channels have been associated with the development of cardiovascular diseases. The purpose of this study was to investigate the effects of Dangkwisoo-san, ginger and curcumin on TRPM7 channel. Methods: Human embryonic kidney (HEK) 293 cells stably transfected with the TRPM7 expression vectors were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1% penicillin/streptomycin, $5{\mu}g/mL$ blasticidin, and 0.4 mg/mL zeocin in a humidified 20% $O_2$/10% $CO_2$ atmosphere at $37^{\circ}C$. Whole-cell patch clamp recordings were obtained using an Axopatch 700B amplifier and pClamp v.10.4 software, and signals were digitalized at 5 kHz using Digidata 1422A. Results: Dangkwisoo-san extract (100, 200, 300, 400, and $500{\mu}g/mL$) inhibited the outward and inward TRPM7 whole-cell currents at dose dependent manner and the half maximal inhibitory concentration $(IC)_{50}$ of Dangkwisoo-san was $218.3{\mu}g/mL$. Also, ginger extract (100, 200, 300, 400, and $500{\mu}g/mL$) inhibited the outward and inward of TRPM7 whole-cell currents in a dose dependent manner and the $IC_{50}$ of ginger was $877.2{\mu}g/mL$. However, curcumin had no effects on TRPM7 whole-cell currents. Conclusions: These results suggest that both Dangkwisoo-san and ginger have good roles to inhibit the TRPM7 channel, suggesting that Dangkwisoo-san and ginger are considered one of the candidate agents for the treatment of metabolic syndrome such as cardiovascular disease.