• Title, Summary, Keyword: C57BL/KsJ-db/db mice

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Sargassum coreanum extract alleviates hyperglycemia and improves insulin resistance in db/db diabetic mice

  • Park, Mi Hwa;Nam, Young Hwa;Han, Ji-Sook
    • Nutrition Research and Practice
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    • v.9 no.5
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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.

Anti-diabetic Effect and Mechanism of Korean Red Ginseng in C57BL/KsJ db/db Mice

  • Yuan, Hai-Dan;Shin, Eun-Jung;Chung, Sung-Hyun
    • Journal of Ginseng Research
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    • v.32 no.3
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    • pp.187-193
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    • 2008
  • The present study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice. The db/db mice were divided into three groups: diabetic control group (DC), Korean red ginseng group (KRG, 100 mg/kg) and metformin group (MET, 300 mg/kg), and treated with drugs once per day for 10 weeks. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in KRG-, 67.7% in MET-treated group. With decreased plasma glucose and insulin levels, the insulin resistance index of the KRG-treated group was reduced by 27.6% compared to the DC group. The HbA1c levels in KRG and MET-treated groups were also decreased by 11.0% and 18.9% compared to that of DC group, respectively. Plasma triglyceride and non-esterified fatty acid levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the KRG-treated group compared to those in DC group. Histological analyses of the liver and fat tissue of mice treated with KRG revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the DC group. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin contents, but decreased glucagon production. To elucidate action mechanism of KRG, effects on AMP-activated protein kinase (AMPK) and its downstream target proteins responsible for fatty acid oxidation and gluconeogenesis were explored in the liver. KRG activated AMPK and acetyl-coA carboxylase (ACC) phosphorylations, resulting in stimulation of fatty acid oxidation. KRG also caused to down regulation of SREBP1a and its target gene expressions such as FAS, SCD1 and GPAT. In summary, our results suggest that KRG exerted the anti-diabetic effect through AMPK activation in the liver of db/db mice.

A Vinegar-processed Ginseng Radix (Ginsam) Ameliorates Hyperglycemia and Dyslipidemia in C57BL/KsJ db/db Mice

  • Han, Eun-Jung;Park, Keum-Ju;Ko, Sung-Kwon;Chung, Sung-Hyun
    • Food Science and Biotechnology
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    • v.17 no.6
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    • pp.1228-1234
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    • 2008
  • Having idea to develop more effective anti-diabetic agent from ginseng root, we comprehensively assessed the anti-diabetic activity and mechanisms of ginsam in C57BL/KsJ db/db mice. The db/db mice were divided into 4 groups; diabetic control (DC), ginsam at a dose of 300 or 500 mg/kg (GS300 or GS500) and metformin at a dose of 300 mg/kg (MT300). Ginsam was orally administered for 8 weeks. GS500 reduced the blood glucose concentration and significantly decreased an insulin resistance index. In addition, GS500 reduced the plasma non-esterified fatty acid, triglyceride, and increased high density lipoprotein-cholesterol as well as decreased the hepatic cholesterol and triglyceride. More interestingly, ginsam increased the plasma adiponectin level by 17% compared to diabetic control group. Microarray, quantitative-polymerase chain reaction and enzyme activity results showed that gene and protein expressions associated with glycolysis, gluconeogenesis, and fatty acid oxidation were changed to the way of reducing hepatic glucose production, insulin resistance and enhancing fatty acid $\beta$-oxidation. Ginsam also increased the phosphorylation of AMP-activated protein kinase and glucose transporter expressions in the liver and skeletal muscle, respectively. These changes in gene expression were considered to be the mechanism by which the ginsam exerted the anti-diabetic and anti-dyslipidemic activities in C57BL/KsJ db/db mice.

Effect of Genistein and Daidzein on Antioxidant Defense System in C57BL/KsJ-db/db Mice (Genistein과 Daidzein 급여가 제2형 당뇨동물모델의 적혈구와 조직 중의 항산화방어계에 미치는 영향)

  • Park, Sun-Ae;Kim, Myung-Joo;Jang, Joo-Yeun;Choi, Myung-Sook;Yeo, Ji-Young;Lee, Mi-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.9
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    • pp.1159-1165
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    • 2006
  • Our preliminary study showed that genistein and daidzein improved blood glucose level in type 2 diabetic mice by enhancing the glucose and lipid metabolism. The objective of this study was to evaluate whether genistein and daidzein are associated with alterations in antioxidant defense mechanism of type 2 diabetic mice. Male C57BL/KsJ-db/db (db/db) mice and age-matched non-diabetic littermates (db/+) were used in this study. The db/db mice were divided into control, genistein (0.02%, w/w) and daidzein (0.02%, w/w) groups. The relative weights of liver, epididymal adipose tissue and perirenal adipose tissue were significantly higher in the db/db group than in the db/+ group, whereas heart weight was lower. The genistein and daidzein supplement did not affect the organ weights in db/db mice. The blood glucose level was positively correlated with superoxide dismutase (SOD, r=0.380, p<0.05) and catalase (CAT, r=0.345, p<0.05) activities and negatively correlated with glutathione peroxidase (GSH Px, r= 0.404, p<0.05) activity in erythrocyte. Therefore, the erythrocyte SOD and CAT activities were significantly elevated in the db/db group compared to the db/+ group and the GSH-Px activity was lowered. However, the supplementation of genistein and daidzein reversed erythrocyte CAT and GSH-Px activities in type 2 diabetic mice. In this current study, the SOD activities in liver, kidney and heart were significantly not different between the groups. The CAT and GSH-Px activities in liver and GSH-Px activity in kidney were significantly higher in the db/db group than in the db/+ group, while the CAT activity in kidney, CAT and GSH-Px activities in heart were lowered. The supplementation of genistein and daidzein significantly attenuated the changes of CAT and/or GSH-Px activities in liver and heart. The supplementation of genistein and daidzein elevated GSH levels in kidney and heart compared to the db/db control group. The lipid peroxide levels in liver, kidney and heart were significantly lowered in the genistein and daidzein supplemented groups compared to the db/db control group. These results suggest that genistein and daidzein might be beneficial for the prevention of type 2 diabetic complication via suppressing changes of antioxidant enzymes activities with simultaneous reduction of lipid peroxidation.

Anti-diabetic Activities of Kocat-D1 in 3T3-L1 Adipocytes and C57BL/KsJ-db/db Mice (3T3-L1 Adipocyte와 C57BL/KsJ-db/db Mice에서 KOCAT-D1의 항당뇨 활성)

  • Yang, Ji-Hee;Won, Hye-Jin;Park, Ho-Young;Nam, Mi-Hyun;Lee, Hyun-Sun;Lee, Joong-Ku;Kim, Jong-Tak;Lee, Kwang-Won
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.5
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    • pp.692-698
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    • 2010
  • This study investigated anti-diabetic activity of Kocat-D1, which is a currently used traditional medicine for treatment of diabetes in Shandong, China. Insulin sensitizing activity was observed in a cell-based glucose uptake assay using 3T3-L1 adipocytes. The treatment of 0.2 mg/mL of hot water extract of Kocat-D1 with 0.2 nM insulin was associated with a significant increasing in glucose uptake ($165.0{\pm}0.7%$) over the treatment of 0.2 nM insulin. C57BL/KsJ-db/db mice (8 weeks of age) were separated into 3 groups: normal control (control, db/+ mice untreated), diabetic control (DM control, db/db mice untreated), Kocat-D1 (db/db mice treated with Kocat-D1 extract 350 mg/kg/day). After 16 weeks of treatment, body weight and total diet intake of Kocat-D1 group were significantly lower than DM control groups. Blood glucose levels of the Kocat-D1 group ($14.7{\pm}1.4\;mmol/L$) were significantly lower compared to the DM control group ($27.1{\pm}0.2\;mmol/L$). Furthermore, insulin level was significantly increased in the Kocat-D1 group ($0.17{\pm}0.02\;ng/mL$) compared with the DM control group ($0.05{\pm}0.02\;ng/mL$). The glomeruli in kidney was stained using periodic acid-shiff base (PAS) for confirming collagen accumulation. The glomeruli in kidney of Kocat-D1 group had significantly reduced PAS-positive compared with that of DM control.

Effects of Silk Protein Hydrolysates on Blood Glucose and Serum Lipid in db/db Diabetic Mice (실크단백질 효소 가수분해물이 2형 당뇨 마우스의 혈당 및 혈청지질에 미치는 영향)

  • Shin, Mi-Jin;Park, Min-Jeong;Youn, Myung-Sub;Lee, Young-Sook;Nam, Moon-Suk;Park, In-Sun;Jeong, Yoon-Hwa
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.10
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    • pp.1343-1348
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    • 2006
  • This study was performed to investigate the effects of silk protein enzyme hydrolysates on blood glucose and serum lipid in db/db diabetic mice. Twelve week-old-male C57BL/KsJ db/db mice were divided into two groups: diabetic control group and 0.25% silk protein hydrolysates solution group, which were fed for 8 weeks. Body weight increased in the silk protein hydrolysates group compared with the diabetic control group. There were no differences in food and water intake between the diabetic control and the silk protein hydrolysates groups. The weight of liver increased in the silk protein hydrolysates group while that of kidney increased in the diabetic control group. The blood glucose level increased about 18.0% in the diabetic control group after 8 weeks while that in the silk protein hydrolysates group increased about 5.8%. Also, silk protein hydrolysates improved the glucose tolerance in C57BL/KsJ db/db mice. There was no difference in total cholesterol and non-HDL cholesterol concentration between the diabetic control and the silk protein hydrolysates group. Triglyceride concentration were lower in the silk protein hydrolysates group than in the diabetic control group (p<0.05) while HDL-cholesterol concentration were higher in the silk protein hydrolysates group than in the diabetic control group (p<0.05). This results suggest that administration of silk protein enzyme hydrolysates reduces significantly an increasing rate of 1]food glucose, decreases triglyceride, and increases HDL-cholesterol in C57BL/KsJ db/db mice.

Gynura procumbens extract improves insulin sensitivity and suppresses hepatic gluconeogenesis in C57BL/KsJ-db/db mice

  • Choi, Sung-In;Lee, Hyun-Ah;Han, Ji-Sook
    • Nutrition Research and Practice
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    • v.10 no.5
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    • pp.507-515
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    • 2016
  • BACKGROUND/OBJECTIVES: This study was designed to investigate whether Gynura procumbens extract (GPE) can improve insulin sensitivity and suppress hepatic glucose production in an animal model of type 2 diabetes. MATERIALS/METHODS: C57BL/Ksj-db/db mice were divided into 3 groups, a regular diet (control), GPE, and rosiglitazone groups (0.005 g/100 g diet) and fed for 6 weeks. RESULTS: Mice supplemented with GPE showed significantly lower blood levels of glucose and glycosylated hemoglobin than diabetic control mice. Glucose and insulin tolerance test also showed the positive effect of GPE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in mice supplemented with GPE than in the diabetic control mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and PM-glucose transporter type 4 increased in mice supplemented with GPE when compared to that of the diabetic control mice. GPE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. CONCLUSIONS: These findings demonstrate that GPE might improve insulin sensitivity and inhibit gluconeogenesis in the liver.

Effects of Inonotus Obliqua Extract on Blood Glucose Levels in Genetically Diabetic Mice (차가버섯 추출물이 당뇨생쥐 $(C57BL/KsJ^-m^{+/+}Lepr^{db})$의 혈당수준에 미치는 영향)

  • Hong, Hee-Ok
    • Journal of Nutrition and Health
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    • v.40 no.7
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    • pp.601-605
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    • 2007
  • This study investigated the therapeutic effects of Inonotus obliqua extract on blood glucose, insulin, and other biochemical parameters in genetically diabetic mice $(C57BL/KsJ^-m^{+/+}Lepr^{db})$. The mice were divided into four groups-control, Chaga 1 (dose of 0.09 mg/kg of body weight), Chaga 5 (5 times of Chaga 1), and Chaga 10 (10 times of Chaga 1) - according to supplemented dose. Inonotus obliqua extract was orally administered to the animals for 6 weeks. The body and organ (liver and kidney) weights were not different among groups. Fasting blood glucose level was significantly lower in the Chaga 5 group compared with the control (p < 0.05). Hemoglobin A1c content was significantly lower in the Chaga 5 group compared with either the control and Chaga 1 group (p < 0.05). There was no significant difference in serum insulin level among groups. The glucose-6-phosphatase activity in liver was significantly the lowest in Chaga 10 group and was significantly lower in Chaga 5 group as compared with those of control and Chaga 1 groups. Therefore, the results of this study demonstrate that Inonotus obliqua extract alleviates many of the symptoms of diabetes in genetically obese mice and may offer a possibility as a therapeutic supplement for the normalization of blood glucose levels in human with hyperglycemia and have beneficial effects in patients with non-insulin-dependent diabetes mellitus.

Anti-diabetic effect of purple corn extract on C57BL/KsJ db/db mice

  • Huang, Bo;Wang, Zhiqiang;Park, Jong Hyuk;Ryu, Ok Hyun;Choi, Moon Ki;Lee, Jae-Yong;Kang, Young-Hee;Lim, Soon Sung
    • Nutrition Research and Practice
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    • v.9 no.1
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    • pp.22-29
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    • 2015
  • BACKGROUND/OBJECTIVES: Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS: The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS: Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2-fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic ${\beta}$-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS: Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic ${\beta}$-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice.