• Title/Summary/Keyword: Diabetic mouse

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Effects of quercetin on the improvement of lipid metabolism through regulating hepatic AMPK and microRNA-21 in high cholesterol diet-fed mice (고콜레스테롤 식이 섭취 쥐에서 quercetin의 간 AMPK 및 microRNA-21 조절을 통한 지질대사 개선 효과)

  • Lee, Mak-Soon;Kim, Yangha
    • Journal of Nutrition and Health
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    • v.55 no.1
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    • pp.36-46
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    • 2022
  • Purpose: Quercetin is a polyphenolic flavonoid abundant in many fruits and vegetables. It has potential health-beneficial properties, such as antioxidant, anti-obesity, anti-cancer, anti-diabetic and anti-inflammatory effects. The purpose of this study was to investigate whether the lipid metabolism improvement effect of quercetin affected the regulation of AMP-activated protein kinase (AMPK) activity and microRNA (miR)-21 expression in the liver of mice fed a high-cholesterol diet. Methods: Male C57BL/6J mice were fed with normal diet, quercetin-free diet and diets containing 0.05% or 0.1% quercetin for six weeks. Hypercholesterolemia was induced by adding 1% cholesterol and 0.5% cholic acid to all diets. Serum and liver triglyceride (TG), and total cholesterol (TC) concentrations were analyzed using a commercial enzymatic colorimetric kit. AMPK activity was quantified using an AMPK kinase assay kit. The levels of miR-21 and genes involved in lipid metabolism were measured by real-time quantitative polymerase chain reaction. Results: Supplementation of quercetin reduced serum and hepatic TG and TC levels without changing body weight and food intake. Dietary quercetin significantly inhibited the mRNA levels of hepatic sterol-regulatory element binding protein-1c, acetyl-CoA carboxylase 1 and fatty acid synthesis, which are involved in hepatic lipogenesis. Dietary quercetin enhanced AMPK activity and suppressed miR-21 expression, promoting hepatic lipid accumulation. Conclusion: These results suggest that the lipid-lowering effect of quercetin on the serum and liver of mice may be partially mediated by the regulation of lipogenic gene expression, AMPK activity and miR-21 expression in the liver of mice fed a high-cholesterol diet.

The Herbal Formula C-DM3 Improves the Changes of Diabetes-Related Biomarkers in High-Fat Diet-Induced Obese Mice through Regulation of the IRS1/PI3K/AKT and AMPK Signaling Pathways in the Liver and Pancreas (고지방식이를 통해 비만이 유발된 마우스에서 C-DM3 복합추출물의 항비만 및 항당뇨 효능 연구)

  • Yoon Yong Choi;Chenzi Lyu;Tong Zhang;Haifeng Shao;Xianglong Meng;Chu Duc Thanh;Jong-Seong Kang;Hyo Won Jung;Yong-Ki Park
    • Journal of Korean Medicine for Obesity Research
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    • v.24 no.1
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    • pp.25-40
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    • 2024
  • Objectives: In the present study, we investigated the effects of clean-diabetes mellitus 3 (C-DM3), a herbal formula with Trichosanthis Radix, Coptidis Rhizoma, Crataegi Fructus, and Cinnamomi Cortex, on the pathological and serological symptoms of diabetes and its related molecular mechanisms in diet-induced obese mice. Methods: We prepared an obese mouse model using a high-fat diet for 8 weeks and then administered the C-DM3 extract for 4 weeks. The changes of pathological and serological biomarkers for diabetes assessment were measured in the mice and histological changes were observed in the liver and pancreas tissues. We also identified the main compounds in the C-DM3 extract using high pressure liquid chromatography (HPLC) and analyzed the molecular mechanism of the disease condition by network pharmacological analysis. Results: In the in vivo, the administration of C-DM extract to obese mice significantly reduced body weight gain, fatty liver symptoms, and muscle loss, and decreased the levels of fasting blood glucose, insulin, aspertate aminotransferase, triglycerides, and low-density lipoprotein-cholesterol. In addition, C-DM extract significantly increased the phosphorylation of insulin receptor substrate 1, protein kinase b (AKT), phosphoinositide 3-kinase (PI3K), adenosine monophosphate-activated protein kinase, and glucose transporter 4 in all pancreatic and liver tissues, with inhibition of histopathological changes in obese mice. HPLC analysis identified hyperoside, berberine, epiberberine, columbamin, coptisine, coumarin, jatrorrhizine, and citric acid as the main compounds. In the network pharmacological analysis, the molecular targets of C-DM3 extract on obesity and diabetes were shown as the insulin, AKT, PI3K, and mitogen-activated protein kinase pathways with the regulation of inflammatory molecules interleukin 6 (IL-6), jun proto-oncogene, and IL-1β, which matched our in vivo targets. Conclusions: Based on these results, C-DM3 extract is expected to be effective in improving obesity and preventing diabetic progression.

Effects of Silk Protein Hydrolysates on Blood Glucose in C57BL/KsJ db/db Mice (실크단백질 효소 가수분해물이 2형 당뇨 마우스 C57BL/KsJ db/db의 혈당에 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.9
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    • pp.1166-1171
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    • 2006
  • This study was performed to investigate the effect of silk protein hydrolysates on blood glucose in diabetic mice (C57BL/KsJ db/db). The silk protein hydrolysates hydrolyzed by protease contains 87.52% of peptides of which molecular weight was below 2,000 dalton. The content of free amino acids was 14.80 g/100 g silk protein hydrolysates and major free amino acids were Pro, Thr, Arg and Ala. Silk protein hydrolysates were administered to the animals for 9 weeks at doses of 0.2, 0.5% and 0.8% solution. The body weight increase in the 0.5 and 0.8% fed groups were higher than control group. Food and water intake in the silk protein hydrolysates fed groups were lower than control group. The weight of liver was not different among groups, while the weight of kidney in control group was higher than silk protein hydrolysates fed groups. The blood glucose level in silk protein hydrolysates fed groups was lower than control group. In the glucose tolerance test, the blood glucose level in control group was the highest at 15 minutes after glucose injection while those in silk protein hydrolysates fed groups were the highest at 30 minutes. Results in this study suggest that silk protein hydrolysates show hypoglycemic effect in C57BL/KsJ db/db mice.

Effects of Pine Needle Extract Oil on Blood Glucose and Serum Insulin Levels in db/db Mice (2형 당뇨 마우스에서 솔잎 추출용액의 경구투여가 혈당조절에 미치는 영향)

  • Kim, Mi-Joung;Ahn, Jin-Hong;Choi, Kang-Ho;Lee, Yun-Hak;Woo, Gyeong-Jin;Hong, Eun-Kyung;Chung, Young-Shin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.3
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    • pp.321-327
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    • 2006
  • This study was performed to investigate the hypoglycemic effect of pine needle extract oil against type 2 diabetes. Six-week-old male C57BL/Ks(db/db) mice were divided into four groups : negative control, pine needle extract oil low dose, high dose and positive control groups, which fed daily for 6 weeks with corn oil, pine needle extract oil 112.5 mg/kg, 450 mg/kg or metformin (150 mg/kg ), respectively. The oral administration of the pine needle extract oil resulted in the significant and dose-dependent decreases of blood glucose levels in comparison with corn oil treatment. The levels of HbAlc showed a tendency of the decrease by the high dose treatment of the pine needle extract oil and were positively correlated with blood glucose levels (r=0.5046, p=0.0023) . However, the levels of serum insulin and C-peptide were not affected by pine needle extract oil or metformin treatments. The levels of serum leptin, which is related with the insulin sensitivity, showed a tendency of the increases by pine needle extract oil treatment and were negatively correlated to blood glucose levels (r=-0.4754, p=0.0052). In conclusion, these results suggest that the pine needle extract oil have a potential for the oral anti-hyperglycemic agent and the mode of action may be related with the improvement of the insulin sensitivity through blood leptin.

Amelioration of Plasma Glucose and Cholesterol levels in Db/db Mice by a Mixture of Chinese Herbs (Db/db 마우스 모델에 있어서 한약재조성물의 혈당 및 혈장 콜레스테롤 개선효과)

  • Lee, Jai-Heon;Cho, Chang-Woo;Han, Xiang-Fu;Hwang, Ji-Yeon;Kang, Min-Jung;Joo, Hee-Jeong;Kim, Mi-Eun;Seo, Yeong-Ju;Kim, Jung-In
    • Korean Journal of Medicinal Crop Science
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    • v.16 no.4
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    • pp.225-230
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    • 2008
  • Diabetes mellitus is the fifth leading cause of death among Koreans. Control of hyperglycemia and dyslipidemia is strongly correlated with decrease in risks for cardiovascular diseases, the most common and fatal diabetic complication. The effects of chronic feeding of a mixture of Chinese herbs on blood lipid profile were measured in an animal model of type 2 diabetes mellitus, db/db mice (C57BL/Ks). The Chinese herb mixture was composed of Panax ginseng C. A. Meyer,Astragalus membranaceus, Glycyrrhiza uralensis, Lycium chinense, Morus, Pueraria thunbergiana, Prunella vulgaris var. lilacina, Acanthopanax sessiliflorus, Schizandra chinensis, Scutellaria baicalensis, Dioscorea batatas, Polygonatum doratumvar. pluriflorum, Paeonia lactiflora, and Rehmannia glutinosa in a ratio of 1 : 0.7 : 0.4 : 0.7 :0.4 : 0.7 : 1.1 : 0.9 : 0.4 : 0.4 : 0.7 :0.7 : 0.9 : 0.9. Methanol extract of the Chinese herb mixture was tested for the inhibitory activity against yeast ${\alpha}$-glucosidase in vitro. The Chinese herb mixture extract inhibited ${\alpha}$-glucosidase by 25.2% at the concentration of 0.5mg/mL. Four weekold male db/db mice (n = 14) were fed AIN-93G semipurified diet or diet containing 10% powder of the Chinese herb mixture for 6 weeks after 1 week of adaptation period. Body weight (39.5 ${\pm}$ 1.6 g) and food intake (4.3 ${\pm}$ 0.6 g/day) of the Chinese herb group were not significantly different from those of the control group (40.4 ${\pm}$ 2.6 g and 4.5 ${\pm}$ 0.6 g/day). Consumption of Chinese herb mixture significantly decreased plasma glucose level (442.5 ${\pm}$ 36.0mg/dL) compared with the control group (489.8 ${\pm}$ 34.6 mg/dL, p < 0.05). Plasma cholesterol level (159.2 ${\pm}$ 18.4 mg/dL) of the Chinese herb group was significantly lower than that of the control group (185.4 ${\pm}$ 13.7 mg/dL, p < 0.05). Blood glycated hemoglobin (6.3 ${\pm}$ 0.8%) and plasma triglyceride levels (99.4 ${\pm}$ 15.0mg/dL) of the Chinese herb group were not significantly different from those of the control group (6.7 ${\pm}$ 0.7% and 108.8 ${\pm}$ 11.0mg/dL). Thus, the Chinese herb mixture could be useful in the treatment of diabetes and cardiovascular complications of diabetes.