• Toxicological Research
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• 제29권1호
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• pp.7-14
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• 2013

Betaine supplementation has been shown to alleviate altered glucose and lipid metabolism in mice fed a high-fat diet or a high-sucrose diet. We investigated the beneficial effects of betaine in diabetic db/db mice. Alleviation of endoplasmic reticulum (ER) and oxidative stress was also examined in the livers and brains of db/db mice fed a betaine-supplemented diet. Male C57BL/KsJ-db/db mice were fed with or without 1% betaine for 5 wk (referred to as the db/db-betaine group and the db/db group, respectively). Lean non-diabetic db/+ mice were used as the control group. Betaine supplementation significantly alleviated hyperinsulinemia in db/db mice. Betaine reduced hepatic expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha, a major transcription factor involved in gluconeogenesis. Lower serum triglyceride concentrations were also observed in the db/db-betaine group compared to the db/db group. Betaine supplementation induced hepatic peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase 1a mRNA levels, and reduced acetyl-CoA carboxylase activity. Mice fed a betaine-supplemented diet had increased total glutathione concentrations and catalase activity, and reduced lipid peroxidation levels in the liver. Furthermore, betaine also reduced ER stress in liver and brain. c-Jun N-terminal kinase activity and tau hyperphosphorylation levels were lower in db/db mice fed a betaine-supplemented diet, compared to db/db mice. Our findings suggest that betaine improves hyperlipidemia and tau hyperphosphorylation in db/db mice with insulin resistance by alleviating ER and oxidative stress.

• Nutrition Research and Practice
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• 제9권5호
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• pp.472-479
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• 2015

BACKGROUND/OBJECTIVES: The goal of this study was to examine the effect of Sargassum coreanum extract (SCE) on blood glucose concentration and insulin resistance in C57BL-KsJ-db/db mice. MATERIALS/METHODS: For 6 weeks, male C57BL/KsJ-db/db mice were administrated SCE (0.5%, w/w), and rosiglitazone (0.005%, w/w). RESULTS: A supplement of the SCE for 6 weeks induced a significant reduction in blood glucose and glycosylated hemoglobin concentrations, and it improved hyperinsulinemia compared to the diabetic control db/db mice. The glucokinase activity in the hepatic glucose metabolism increased in the SCE-supplemented db/db mice, while phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities in the SCE-supplemented db/db mice were significantly lower than those in the diabetic control db/db mice. The homeostatic index of insulin resistance was lower in the SCE-supplemented db/db mice than in the diabetic control db/db mice. CONCLUSIONS: These results suggest that a supplement of the SCE lowers the blood glucose concentration by altering the hepatic glucose metabolic enzyme activities and improves insulin resistance.

• Nutritional Sciences
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• 제7권1호
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• pp.8-16
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• 2004

The purpose of this study was to investigate the gene profiles that were up- or down-regulated in the livers of high-fat diet-induced obese mice and $db_-/db_-$ mice with deficient leptin receptor. C57/BL6 normal mice and $db_-/db_-$ mice, respectively, were divided into two groups and fed a standard or high-fat diet for four weeks. Liver weight was unchanged in the normal mice but the high-fat diet led to a 10% weight increase in the $db_-/db_-$mice. Adipose tissue mass increased by about 88% in the normal mice that were fed a high-fat diet and by about 17% in the $db_-/db_-$mice on the high-fat diet. In terms of serum lipids, total cholesterol significantly increased in mice on the high-fat diet. Microarray analysis was carried out using total RNA isolated from the livers of standard or high-fat diet-fed mice of the normal and $db_-/db_-$ strains. The change of gene expression was confirmed by RT-PCR. About 1.6% and 6.8% of total genes, respectively, showed different expression patterns in the normal mice fed the high-fat diet and $db_-/db_-$ mice. As a result of microarray, many genes involved in metabolism and signal pathways were shown to have different expression patterns. Expression of Mgst3 gene increased in the livers of normal and $db_-/db_-$ mice that were fed a high-fat diet. Wnt7b and Ptk9l were down-regulated in the livers of the normal mice and $db_-/db_-$ mice that were fed a high-fat diet. In conclusion, a high-fat diet induced obesity and affected gene expression involved in metabolism and signal pathway.

• 한국식품영양학회지
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• 제25권1호
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• pp.99-104
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• 2012

The goal of this study was to examine the ameliorative effects of black ginseng(BG) in male obese diabetic C57BLKS/ J-db/db mice. Ten-week-old male db/db mice were administrated 300 mg/kg of F-BG daily for 6 weeks, The db/db mice where corresponded to the normal group and db/db mice which were the diabetic positive group were not provided BG treatment. The supressive effects of treatment were examined on serum lipids levels, which included total cholesterol, triglyceride, LDL-cholesterol and nonesterified fatty acid. Also, weight changes and the relative weight of liver and kidney, organ pathological investigation were measured. The effects of treatment were assessed by comparing the results of the db/db mice that received BG for 6 weeks with that of the diabetic positive group. Significant differences in several biological parameters such as HDL level(p<0.05), TG level(p<0.05) and NEFA level(p<0.05) were observed for the BG group. BG treatment increased the HDL level and decreased the NEFA level, which could ameliorate hyperlipidemia or blood circulation.

• 생약학회지
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• 제33권4호통권131호
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• pp.332-336
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• 2002

Opuntia ficus-indica var. sabotan was administered with diet for 5 weeks on db/db diabetic mice and its antidiabetic activity was investigated. Leaves of Opuntia ficus-indica var. sabotan inhibited the increase of body weight, glucose elevation in blood and urine, and protein excretion in urine, and protein excretion in urine. Opuntia ficus-indica var. sabotan also inhibited the intestinal maltase and sucrase activity on db/db Mice loaded with maltose and sucrose. However, it did not significantly lower HbAlc in blood of db/db mice. These results suggest that leaves of Opuntia ficus-indica var. sabotan could be effective on insulin-independent diabetic mellitus type 2.

• Nutrition Research and Practice
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• 제18권1호
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• pp.88-97
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• 2024

BACKGROUND/OBJECTIVES: Mitigating insulin resistance and hyperglycemia is associated with a decreased risk of diabetic complications. The effect of Daraesoon (shoot of hardy kiwi, Actinidia arguta) on hyperglycemia was investigated using a type 2 diabetes animal model. MATERIALS/METHODS: Seven-week-old db/db mice were fed either an AIN-93G diet or a diet containing 0.4% of a 70% ethanol extract of Daraesoon, whereas db/+ mice were fed the AIN-93G diet for 7 weeks. RESULTS: Consumption of Daraesoon significantly reduced serum glucose and blood glycated hemoglobin levels, along with homeostasis model assessment for insulin resistance in db/db mice. Conversely, Daraesoon elevated the serum adiponectin levels compared to the db/db control group. Furthermore, Daraesoon significantly decreased both serum and hepatic triglyceride levels, as well as serum total cholesterol levels. Additionally, consumption of Daraesoon resulted in decreased hepatic tumor necrosis factor-α and monocyte chemoattractant protein-1 expression. CONCLUSIONS: These results suggest that hypoglycemic effect of Daraesoon is mediated through the improvement of insulin resistance and the downregulation of pro-inflammatory cytokine expression in db/db mice.

• 한국축산식품학회지
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• 제36권2호
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• pp.170-177
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• 2016

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. CLA has been reported to be able to reduce body fat. In this study, we investigated the antidiabetic effect of fermented milk (FM) containing CLA on type II diabetes db/db mice. Mice were treated with 0.2% low FM, 0.6% high FM, or Glimepiride (GLM) for 6 wk. Our results revealed that the body weight and the levels of fasting blood glucose, serum insulin, and leptin were significantly decreased in FM fed mice compared to db/db mice. Oral glucose tolerance and insulin tolerance were significantly ameliorated in FM fed mice compared to db/db mice. Consistent with these results, the concentrations of serum total cholesterol, triglycerides, and LDL cholesterol were also significantly decreased in FM fed mice compared to db/db mice. However, the concentration of HDL cholesterol was significantly higher in FM fed mice compared to db/db mice. These results were similar to those of GLM, a commercial anti-diabetic drug. Therefore, our results suggest that FM has anti-diabetic effect as a functional food to treat type II diabetes mellitus.

• 대한한방내과학회지
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• 제37권3호
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• pp.467-483
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• 2016

Objective: This study was performed to investigate the effect of IUS (Inulsan, an extract of Artemisiae capillaris (茵蔯), Curcumae longae (鬱金), and Crataegi fructus (山査)) on anti-hyperlipidemia, anti-oxidation, and anti-inflammation.Method: We administered water extracts of Artemisiae capillaris, Curcumae longae, and Crataegi fructus for three weeks to db/db mice (C57BL/Ks), animal models induced with type 2 diabetes mellitus. Mice were divided into three groups: normal (C57BL/6J mice group), control group (db/db mice without administration of IUS) and IUS group (db/db mice treated with IUS). Then we measured total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride in the serum after the oral administration of IUS.Results: 1. IUS did not show any cytotoxicity in RAW 264.7 cells. 2. IUS decreased AST, ALP, and creatinine levelsand did not show any liver or renal toxicity in the db/db mice. 3. IUS increased DPPH and ABTS radical scavenging activity and decreased ROS production in RAW 264.7 cells. 4. IUS significantly decreased IL-1β, IL-6, and TNF-α production in RAW 264.7 cells. 5. IUS increased HDL cholesterol and significantly decreased total cholesterol and triglyceride in db/db mice. 6. IUS significantly decreased the atherogenic index and cardiac risk factor. 7. In contrast with the control group, fat infiltration in the liver and aorta decreased in IUS treated mice. The cell nucleus was located in the central area in H&E staining of liver. And endomembranes also were more thinner than the control group in H&E staining of aorta.Conclusions: These results suggest that IUS might be effective in the prevention and treatment of dyslipidemia.

• Journal of Ginseng Research
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• 제47권6호
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• pp.784-794
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• 2023

Background: ginsenoside Rg5 is a rare ginsenoside with known hypoglycemic effects in diabetic mice. This study aimed to explore the effects of ginsenoside Rg5 on skin wound-healing in the Lepr^db/db mutant (db/db) mice (C57BL/KsJ background) model and the underlying mechanisms. Methods: Seven-week-old male C57BL/6J, SLC7A11-knockout (KO), the littermate wild-type (WT), and db/db mice were used for in vivo and ex vivo studies. Results: Ginsenoside Rg5 provided through oral gavage in db/db mice significantly alleviated the abundance of apoptotic cells in the wound areas and facilitated skin wound healing. 50 μM ginsenoside Rg5 treatment nearly doubled the efferocytotic capability of bone marrow-derived dendritic cells (BMDCs) from db/db mice. It also reduced NF-κB p65 and SLC7A11 expression in the wounded areas of db/db mice dose-dependently. Ginsenoside Rg5 physically interacted with SLC7A11 and suppressed the cystine uptake and glutamate secretion of BMDCs from db/db and SLC7A11-WT mice but not in BMDCs from SLC7A11-KO mice. In BMDCs and conventional type 1 dendritic cells (cDC1s), ginsenoside Rg5 reduced their glycose storage and enhanced anaerobic glycolysis. Glycogen phosphorylase inhibitor CP-91149 almost abolished the effect of ginsenoside Rg5 on promoting efferocytosis. Conclusion: ginsenoside Rg5 can suppress the expression of SLC7A11 and inhibit its activity via physical binding. These effects collectively alleviate the negative regulations of SLC7A11 on anaerobic glycolysis, which fuels the efferocytosis of dendritic cells. Therefore, ginsenoside Rg5 has a potential adjuvant therapeutic reagent to support patients with wound-healing problems, such as diabetic foot ulcers.

• 한국식품영양과학회지
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• 제42권6호
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• pp.861-868
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• 2013

유전적으로 제2형 당뇨병이 유발되는 db/db 생쥐에 OF를 5% 수준으로 4주간 급여한 결과 지방 대사를 개선시켜, 혈장 총콜레스테롤, LDL-콜레스테롤, VLDL-콜레스테롤과 중성지방을 유의적으로(p<0.05) 감소시켰고, HDL-콜레스테롤은 유의적인 차이를 보이지 않았다. 혈장 총콜레스테롤의 감소는 간에서 HMG-CoA-R의 감소에 의한 콜레스테롤의 생성이 줄어든 것이고, 또한 콜레스테롤을 담즙산으로 합성하는 CYP7A1을 증가시켜 콜레스테롤을 담즙산의 형태로 배설시켰기 때문이다. 이 결과 분변 중 담즙산의 함량이 증가하였다. LDL-콜레스테롤의 감소는 LDL-콜레스테롤을 세포로 이동시켜 분해를 촉진하는 LDL-R의 증가로 확인할 수 있었다. db/db mice에서는 비만뿐 아니라 심각한 지방간이 유발되는데 OF의 급여로 AST와 ALT를 낮추어 간세포의 파괴를 완화시켰으며, 간 조직의 H&E 염색 소견에서도 지방간의 완화를 확인할 수 있었다. 또한 대조군으로 C57 생쥐에게 5% 수준으로 OF를 급여한 결과 OF를 급여하지 않은 대조군과 OF를 급여한 실험군의 혈장 중성지방, 총 콜레스테롤, HDL-콜레스테롤, LDL-콜레스테롤, VLDL-콜레스테롤, AST와 ALT 함량의 차이가 없었으며, 간조직 관찰에서도 차이를 나타내지 않았다. 이상의 결과를 종합할 때, OF는 당뇨병이 유발되지 않은 정상혈당의 생쥐에서는 지질대사에 아무런 영향을 주지 않았으며, 제2형 당뇨병인 db/db mice의 당뇨병 합병증인 지질대사 이상을 개선하는데 효과가 있는 것으로 사료되며, OF의 어떤 성분이 이와 같은 효과를 나타냈는지 보다 구체적인 성분 분석과 세부적인 연구를 통한 확인이 필요하다고 사료된다.