• Advances in Traditional Medicine
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• 제10권3호
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• pp.165-172
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• 2010

The present study investigated the effect of silymarin, a flavonoid, on streptozotocin (STZ) - induced diabetic dyslipidaemia in rats. Experimental diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Silymarin (25 mg/kg and 50 mg/kg) was orally administered to diabetic rats for a period of 15 days. Blood glucose levels, serum lipid profile and liver glycogen levels were estimated following the established procedures. Biochemical observations were supplemented with histological examination of liver sections. Oral administration of silymarin to diabetic rats significantly (P < 0.001) decreased the blood glucose levels ($259.99{\pm}23.64$ vs. $99.90{\pm}2.62$ [25 mg] & $89.17{\pm}3.32$ [50 mg]). The most interesting finding was the significant (p < 0.001) increase in HDL-cholesterol levels ($26.99{\pm}0.61$ vs. $40.55{\pm}0.52$ [25 mg] & $41.12{\pm}0.37$ [50 mg]) whereas, there was a significant decrease in serum total cholesterol (TCh), triglycerides (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol levels observed in silymarin treated diabetic rats. STZ treatment caused significant degeneration of liver parenchyma, which was normalized to near normal morphology by administration of silymarin. The findings indicate that silymarin effectively improved the overall lipid profile and restored the glycogen stores in the liver of STZ-induced diabetic rats, in a dose dependent manner. The results indicate existence of abnormalities in lipid metabolism in STZ-induced diabetic rats and suggest a protective effect of silymarin in this animal model.

• Journal of Dairy Science and Biotechnology
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• 제39권2호
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• pp.78-85
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• 2021

본 연구는 고지방식이 마우스에서 체중 감소, 혈당 감소 및 인슐린 저항성 개선 효과를 가지는 LNS1 균주의 간 내 글리코겐 함량에 미치는 영향을 조사하여 고지방식이에 의한 비정상적인 글리코겐 대사 개선을 위한 활용 가능성을 검토하고자 실시하였다. LNS1을 12주간 경구 투여한 고지방식이 마우스의 간에서 포도당 운반체 단백질인 GLUT2와 글리코겐 합성의 주요 효소인 GCK, GYS2의 유전자 발현 변화를 확인한 결과, LNS1의 경구 투여는 고지방식이 마우스에 비해 GLUT2와 GYS2의 유전자 발현을 각각 약 2배, 1.8배 증가시켰으며, GCK의 발현에는 영향을 주지 않는 것으로 확인되었다. 또한, GCK의 regulatory unit으로 작용하여 GCK의 활성을 억제하는 GCKR와 글리코겐 분해 과정의 주요 효소인 G6PC의 발현은 LNS1 투여에 의해 HFD마우스에 비해 각각 약 53%, 32% 감소함을 보였다. 간 조직에서의 결과와 마찬가지로 HepG2 세포에 LNS1-CM의 처리는 GLUT2와 GYS2의 유전자 발현을 약 1.9배, 2배 증가시켰으며, GCK의 발현 변화에는 영향을 주지 않는 것으로 확인되었다. GCKR과 G6PC의 유전자 발현 또한 LNS1-CM 처리에 의해 각각 77%, 47% 감소함을 보였다. 또한, 간 조직 내 글리코겐 함량은 고지방식이와 LNS1 투여를 병행한 마우스에서 고지방식이 마우스에 비해 약 1.5배 증가한 것으로 조사되었다. 위의 결과들을 종합해 볼 때, LNS1은 GLUT2, GYS2, GCKR와 G6PC의 발현 조절을 통해 간 조직내 글리코겐 함량을 증가시켜 고지방식이에 의한 글리코겐 대사 이상을 개선시키는 효과를 가지는 것으로 사료된다.

• Clinical and Experimental Pediatrics
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• 제52권11호
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• pp.1279-1282
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• 2009

당뇨병 환자에서 간비대와 간 기능 이상이 동반될 경우 간 내 당원축적증과 비알콜성 지방간염을 감별해야 한다. 저자들은 인슐린 치료를 제대로 받지 않아 혈당 조절이 불량한 환자에서 저혈당과 간비대로 발현한 간 내 당원축적증을 경험하여 보고한다. 만 6세경 1형 당뇨병으로 진단받은 환아로 10세경 우상복부 통증과 반복되는 고혈당과 저혈당으로 내원하였으며, 당시 진찰상 둥근 얼굴, 우측 늑골연 하방 6 cm 정도에서 만져지는 간비대가 있었다. 검사상 소변 케톤 양성, 당화혈색소는 9.6%였다. 간 효소치가 증가되어 있었고, 혈중 콜레스테롤/중성지방 250/267 mg/dL였다. 바이러스성 간염, 자가면역성 간염, 대사성 간 질환에 대한 검사는 모두 정상이었다. 복부 초음파 및 컴퓨터 단층 촬영상 지방간과 간비대 소견을 보였다. 간 조직 검사상 PAS 염색에서 양성, diastase-PAS 염색에서는 음성으로 전형적인 당원축적증의 소견을 보였다. 고혈당을 보일 때마다 초속효성 인슐린을 투여하고 심한 저혈당의 증상이 동반된 경우 글루카곤을 투여하였으며 생옥수수 전분 가루를 간식으로 먹이면서 저혈당 횟수가 감소하여 퇴원하였다. 현재 외래에서 초속효성 인슐린으로 혈당 조절하면서 관찰 중이다. 제1형 당뇨병 환자에서 당원축적증은 간비대와 간 효소치의 상승을 야기할 수 있는 원인이다. 본 증례에서는 심한 저혈당이 반복되어 하루에도 수 차례 글루카곤을 투여하였으며, 생옥수수 전분 가루을 투여하면서 저혈당이 호전되었다. 엄격한 혈당 관리로 간 비대 및 간 기능 이상이 호전될 수 있으므로 적절한 인슐린 치료로 혈당을 조절하고 저혈당을 예방해야 하겠다.

• Nutrition Research and Practice
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• 제17권4호
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• pp.670-681
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is caused by reactive oxygen species and free radicals that accelerate inflammatory responses and exacerbate fatigue. Tormentic acid (TA) has antioxidant and anti-inflammatory properties. Thus, the aim of present study is to determine the fatigue-regulatory effects of TA in H₂O₂-stimulated myoblast cell line, C2C12 cells and treadmill stress test (TST) and forced swimming test (FST) animal models. MATERIALS/METHODS: In the in vitro study, C2C12 cells were pretreated with TA before stimulation with H₂O₂. Then, malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase (CK) activity, tumor necrosis factor (TNF)-α, interleukin (IL)-6, superoxide dismutase (SOD), catalase (CAT), glycogen, and cell viability were analyzed. In the in vivo study, the ICR male mice were administered TA or distilled water orally daily for 28 days. FST and TST were then performed on the last day. In addition, biochemical analysis of the serum, muscle, and liver was performed. RESULTS: TA dose-dependently alleviated the levels of MDA, LDH, CK activity, TNF-α, and IL-6 in H₂O₂-stimulated C2C12 cells without affecting the cytotoxicity. TA increased the SOD and CAT activities and the glycogen levels in H₂O₂-stimulated C2C12 cells. In TST and FST animal models, TA decreased the FST immobility time significantly while increasing the TST exhaustion time without weight fluctuations. The in vivo studies showed that the levels of SOD, CAT, citrate synthase, glycogen, and free fatty acid were increased by TA administration, whereas TA significantly reduced the levels of glucose, MDA, LDH, lactate, CK, inflammatory cytokines, alanine transaminase, aspartate transaminase, blood urea nitrogen, and cortisol compared to the control group. CONCLUSIONS: TA improves fatigue by modulating oxidative stress and energy metabolism in C2C12 cells and animal models. Therefore, we suggest that TA can be a powerful substance in healthy functional foods and therapeutics to improve fatigue.

• 한국응용과학기술학회지
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• 제31권2호
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• pp.277-284
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• 2014

The ethanol extraction yield of Meliae toosendan fructus(MT) was about 24.5% by extract apparatus. This study was done to investigate the carbohydrate metabolism related enzyme activities and antioxidative effects of MT in streptozotocin (STZ)-induced diabetic rats. The contents of serum glucose, triglyceride (TG) were significantly decreaed in MT treated group compared to the those of STZ-control group, also content of Total cholesterol was decreased. High density lipoprotein (HDL)-cholesterol was increased in MT treated group. The activity of glucose-6-pase(G-6-Pase) was significantly decreased in MT treated group. Also the activities of glucose-6-phosphate dehydrogenase(G-6-PDH) and glucokinase(Gk) were increaed in MT treated group. The content of hepatic glycogen was significantly increaed in MT treated group, in addition, content of malondialdehyde(MDA) was significanly decreased in MT treated group. Also, content of glutathione(GSH)was dereased in MT treated froup. whereas, activity of catalase(CAT) was significantly increaed in MT treated group compared to the those of STZ-control group. activity of glutathione peroxidase(GSH-Px) was inecreaed. In conclusion, these results indicated that ethanol extract of MT would have carbohydrate metabolism antioxidative effects in STZ-induced diabetic rats.

• Animal Bioscience
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• 제35권8호
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• pp.1184-1194
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• 2022

Objective: High concentrate diets are widely used to satisfy high-yielding dairy cows; however, long-term feeding of high concentrate diets can cause subacute ruminal acidosis (SARA). The endocrine disturbance is one of the important reasons for metabolic disorders caused by SARA. However, there is no current report about thyroid hormones involved in liver metabolic disorders induced by a high concentrate diet. Methods: In this study, 12 mid-lactating dairy cows were randomly assigned to HC (high concentrate) group (60% concentrate of dry matter, n = 6) and LC (low concentrate) group (40% concentrate of dry matter, n = 6). All cows were slaughtered on the 21st day, and the samples of blood and liver were collected to analyze the blood biochemistry, histological changes, thyroid hormones, and the expression of genes and proteins. Results: Compared with LC group, HC group showed decreased serum triglyceride, free fatty acid, total cholesterol, low-density lipoprotein cholesterol, increased hepatic glycogen, and glucose. For glucose metabolism, the gene and protein expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 in the liver were significantly up-regulated in HC group. For lipid metabolism, the expression of sterol regulatory element-binding protein 1, long-chain acyl-CoA synthetase 1, and fatty acid synthase in the liver was decreased in HC group, whereas carnitine palmitoyltransferase 1α and peroxisome proliferator activated receptor α were increased. Serum triiodothyronine, thyroxin, free triiodothyronine (FT3), and hepatic FT3 increased in HC group, accompanied by increased expression of thyroid hormone receptor (THR) in the liver. Conclusion: Taken together, thyroid hormones may increase hepatic gluconeogenesis, β-oxidation and reduce fatty acid synthesis through the THR pathway to participate in the metabolic disorders caused by a high concentrate diet.

• Journal of Ginseng Research
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• 제47권3호
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• pp.420-428
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• 2023

Background: Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. Methods: HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. Results: Cell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. Conclusion: Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

• Journal of Genetic Medicine
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• 제4권1호
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• pp.72-79
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• 2007

목 적 : 제3형 당원병은 상염색체 열성으로 유전되는 드문 글리코겐 대사 질환이다. 글리코겐 debranching 효소는 두 가지 효소의 기능을 가지는데, amylo-1,6-glucosidase와 4-alpha-glucanotransferase가 그것이며, 제3형 당원병에서는 글리코겐 debranching 효소의 결핍으로 글리코겐의 불완전한 분해가 초래되며, 다양한 임상 및 생화학적 양상을 보이는 것으로 알려져 있다. 본 연구에서는 3명의 한국인 환자의 임상 및 생화학적 양상을 분석하고, AGL 유전자의 돌연변이 형태를 밝히고자 하였다. 방 법 : 서로 혈연 관계가 없는 3명의 한국인 제3형 당원병 환자를 대상으로, 생화학적, 조직학적, 방사선학적 특징을 포함한 임상 양상을 의무 기록을 통하여 조사하였다. 환자의 말초혈액에서 백혈구를 분리하여 추출한 genomic DNA를 사용하여 직접적 염기 서열 분석법으로 AGL 유전자의 35개 exon 및 exon과 intron의 경계 부분을 조사하여 돌연변이를 조사하였다. 결 과 : 간비대, 경련, 저신장, 고지혈증, 간효소 수치의 증가, creatine kinase 수치의 증가, 경도의 심근증 등 다양한 임상 양상이 관찰되었고, 한 명의 환자는 진행성 간섬유화로 인하여 간이식 수술을 시행 받았다. 생옥수수 전분가루의 복용은 모든 환자에서 정상 혈당을 유지시키고, 생화학적 검사 소견을 개선시키며 정상적인 성장 속도를 보이게 하였다. AGL 유전자 분석 결과 6개의 대립유전자 중 5개에서 돌연변이를 확인할 수 있었으며, 이중에 p.R428K를 제외한 4개의 돌연변이는 이제까지 보고된 적이 없는 새로운 돌연변이(c.1306delA, c.1510-1511insT, c.3416 T>C, c.1735+1 G>T)였다. 결 론 : 제3형 당원병은 임상 증상 및 중등도가 다양한 질환으로, 제1형 당원병의 증상과 유사하여 초기에 감별이 쉽지 않으며, 한국인 환자에서의 AGL 유전자의 돌연변이 양상도 매우 이질적이다.

• 한국작물학회지
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• 제58권4호
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• pp.443-450
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• 2013

Effects of newly developed functional rice grains Goami (high-amylose rice) and Nokwon (green-kerneled rice) on the glucose metabolism and antioxidative defense system in C57BL/6N mice under high fat diet condition were investigated. Animals were randomly divided into five groups (n = 8) and given experimental diets for eight weeks: normal control diet (NC), high fat diet (HF), and high fat diet supplemented with white rice (HF-WR), Goami rice (HF-GR), and Nokwon rice (HF-NR). At the end of the experimental period, the HF group exhibited markedly higher blood glucose level, insulin concentration, plasma lipid peroxidation and lower hepatic glycogen concentration than that exhibited by NC group. However, diet supplementation of Goami and Nokwon suppressed the high fat diet-induced hyperglycemia and oxidative stress through inhibition of the glucose-regulating enzymes and enhancement of the antioxidant enzymes activities. The results illustrate that the new functional rice Goami and Nokwon may be useful in the development of functional foods with preventive effect against high fat diet-induced hyperglycemia and oxidative stress.

• Journal of Ginseng Research
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• 제17권1호
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• pp.13-21
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• 1993

We attempted in this study to understand the hypoglycemic action of the fat soluble fraction of red ginseng roots in streptozotocin injected diabetic rats, through its actions on several enzymes relating to carbohydrate metabolism of the 1eve1 to compare with those of ginsenosides in streptozotocin injected diabetic rats. It was realized that the increased level of glucose, ketone bodies, lactate, nonesterified fatty acids and triacylglycerol in blood was significantly decreased and the decreased liver glycogen content of streptozotocin injected rats were appreciably moderated by intraperitoneal injection of the fat soluble fraction of red ginseng roots as shown in the saponin injected diabetic rats. The deceased activities of liver enzymes relating to carbohydrate metabolism such as phosphofructokinase, glucokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and acetyl CoA carboxylase of streptozotocin induced diabetic rats were also sufficiently modified by the intraperitoneal injection of the above fat soluble fraction as shown in the ginsenoside injected streptozotocin induced rats.