• Title/Summary/Keyword: db/db Mice

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Anti-diabetic Effects of Triticum aestivum L. Water Extracts in db/db Mice as an Animal Model of Diabetes Mellitus Type II (제2형 당뇨모델 db/db 마우스에서 밀순 물추출물의 항당뇨 효과)

  • Lee, Sun-Hee;Lim, Sung-Won;Lee, Young-Mi;Hur, Jung-Mu;Lee, Hoi-Seon;Kim, Dae-Ki
    • Korean Journal of Pharmacognosy
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    • v.41 no.4
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    • pp.282-288
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    • 2010
  • We evaluated the anti-diabetic effects of Triticum aestivum sprout water extract (TA) in diabetes mellitus type 2. For the experiments, the diabetic animal model db/db mice were divided to 3 groups: diabetic control (db/db) and two experimental groups orally treated with 25 and 100 mg/kg single dose of TA (TA-25 and TA-100, respectively). The lean mice were used as the non-diabetic normal control. All mice have free access to water and AIN-93 diet. TA was administrated to diabetic mice for 5 weeks and the diabetic clinical markers, including blood glucose level, body weight, food intake and insulin level, were measured at a time. After administration for 5 weeks, the blood glucose level was decreased 1.10 and 1.98 folds in TA-25 and TA-100 groups, respectively, compared with db/db group. The body weight and diet consumption were significantly reduced by TA treatment in dose-dependent manner. The treatments of TA-100 also significantly decreased remarkedly liver weight and slightly serum insulin levels when compared with them of the diabetic control group. However the immunohistochemical staining for insulin clearly showed high expression of insulin in the pancreatic islet cells derived from all db/db mice, even if TA was administrated. Moreover, TA-100 treatment significantly improved impaired glucose tolerance in diabetic db/db mice. The results suggest that TA has anti-hyperglycemic effect attenuating blood glucose in the animal model of type 2 diabetes and might be useful as a functional diet for human diabetic diseases.

Thermogenesis and cellular senescence of diabetic adipocytes in response to β-agonists and 18-carbon fatty acids

  • Seonjeong Park;Seung A Ock;Yun Jeong Park;Sung Nim Han;Sunhye Shin
    • Journal of Nutrition and Health
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    • v.57 no.4
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    • pp.376-388
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    • 2024
  • Purpose: Adipocyte dysfunction has been reported in diabetes, and stimulating thermogenesis and suppressing senescence in adipocytes potentially alleviates metabolic dysregulation. This study aimed to investigate thermogenesis and cellular senescence in diabetic adipocytes under basal conditions and in response to stimuli. Methods: White and brown primary adipocytes derived from control (CON) and db/db (DB) mice were treated with β-agonists, such as norepinephrine (NE) and CL316,243, and 18-carbon fatty acids, including stearic acid, oleic acid (OLA), linoleic acid (LNA), and α-linolenic acid, and the expression of the genes related to thermogenesis and cellular senescence was measured. Results: Although no difference in the thermogenic and cellular senescence gene expression in white adipose tissue (WAT) was noted between the CON and DB mice, brown adipose tissue (BAT) from the DB mice exhibited lower uncoupling protein 1 (Ucp1) expression and higher cyclin-dependent kinase inhibitor (Cdkn)1a and Cdkn2a expression levels compared to that from the CON mice. Stromal vascular cells isolated from the BAT of the DB mice displayed higher peroxisome proliferator-activated receptor gamma (Pparg), CCAAT/enhancer-binding protein alpha (Cebpa), Cdkn1a, and Cdkn2a expression levels. White adipocytes from the DB mice exhibited lower Ucp1, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (Pgc1a), and PR domain containing 16 (Prdm16) expression levels regardless of β-agonist treatment. NE upregulated Pgc1a in both white and brown adipocytes from the CON mice, but not in those from the DB mice. Although none of the fatty acids were observed to downregulate the cellular senescence genes in fully differentiated adipocytes, the OLA-treated brown adipocytes derived from DB mice exhibited lower Cdkn1a and Cdkn2b expression levels than the LNA-treated cells. Conclusion: These results indicate that the lower thermogenic capacity of diabetic adipocytes may be related to their cellular senescence, and different fatty acids potentially exert divergent effects on the expression of cellular senescence genes.

Antidiabetic Effects of Corni Fructus Extract on Blood Glucose and Insulin Resistance in db/db Mice

  • Kim, Hye-Jeong;Kim, Kil-Soo;Lee, Tae-Jong;Kim, Young-Chul
    • Toxicological Research
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    • v.25 no.2
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    • pp.93-99
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    • 2009
  • This study investigated the effect of Corni Fructus (Cornus officinalis Sieb. et Zucc.) extract on blood glucose and insulin resistance in db/db mice. Seven weeks old male mice were divided into normal control group (NC), diabetic control group (DC) and Corni Fructus treated diabetic group (DCF). Over an 8-week experimental period, Corni Fructus extract was administered orally at 500 mg/kg BW/day. Corni Fructus inhibited increase in blood glucose level during the OGTT (oral glucose tolerance test). At 8 weeks after beginning of the experiment, blood glucose level in the DCF group was significantly lower (p<0.01) than the DC group. Final fasting serum glucose and triglyceride in the DCF group were significantly lower (p<0.05) than the DC group by 32% and 41% respectively. Serum insulin did not differ among the NC, DC and DCF groups. The mRNA expression of adiponectin, GLUT 4 and PPAR-$\gamma$ in adipose tissue in the DC group were significantly lower than the NC group and they were higher in the DCF group than the DC group by 76%, 130% (p<0.05) and 43%, respectively. In conclusion, these results indicated that Corni Fructus would have antidiabetic effects via improving insulin resistance in favor of higher glucose utilization and reducing blood glucose level in db/db mice.

Improvement of blood glucose control in type 2 diabetic db/db mice using Platycodon grandiflorum seed extract (도라지 종자 추출물의 처리가 제2형 당뇨 db/db 마우스의 혈당개선에 미치는 효과)

  • Kim, Tae Yeong;Kim, Seok Joong;Imm, Jee-Young
    • Korean Journal of Food Science and Technology
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    • v.52 no.1
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    • pp.81-88
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    • 2020
  • The biological activities of Platycodon grandiflorum (PG) root extracts have been studied intensively, whereas there are limited number of studies on PG seed extract (PGSE). PGSE was prepared by ethanol extraction, and its antidiabetic effect was evaluated in mice with type 2 diabetes (C57BLKS/J-db/db). Results indicated that the administration of high-dose PGSE (600 mg/kg, wb) significantly stabilized the blood glucose levels, as evidenced by the results of the oral glucose tolerance test. Mice treated with high-dose PGSE exhibited significantly lower serum hemoglobin A1c, insulin, and leptin levels after eight weeks of feeding trial (p<0.05). High-dose PGSE administration significantly improved glucose uptake in the femoral muscle of db/db mice by activating both IRS-1/PI3K/AKT/AS160 and AMPK phosphorylation pathways. GLUT4 translocation from the cytosol to the plasma membrane increased 1.7-fold in the PGSE high-dose group. These results suggest that PGSE has potential for development as an antidiabetic agent.

Antidiabetic Effects of Herbal Medicine on db/db Mice (4종 한약 처방이 db/db 마우스의 혈당 개선에 미치는 영향)

  • Chang Mun Seog;Jin Hyun Sun;Jung Kye Jin;Park Sun Min;Choi Soo Bong;Ko Byoung Seob;Park Seong Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.1
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    • pp.58-62
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    • 2004
  • The effects of herbal medicine on type 2 diabetic animal model were investigated. Herbal medicine were composed with the addition of Coicis Semen into Okchun-san (OCS). Commelinae Herba into Gangsim-tang (GST). Scrophulariae Radix into Hyunsamsunki-san (HSK). and Erythrinae Cortex into Yukmijihuang-hwan (YMH). We evaluated anti-hyperglycemic and body weight reduction activity in diabetic db/db mice. The experimental animals were divided into six groups. as control group and five sample groups. Each 200mg/kg/day of OCS, GST, HSK and YMH was administered with orally for 14days long. 5mg/kg/day of acarbose was administered with orally for 14days long. On day 14, OCS-treated db/db mice had significantly lower fasting blood glucose levels compared to control group(296±25.9 versus 593±16.4mg/dl. p<0.001). During the 2 h intraperitoneal glucose tolerance test (IPGTT), all the sample groups were improved compared to control group but insignificantly. After 14days of extract treatment. body weight in control. YMH and acarbose groups were increased. but OCS. GST and HSK groups reduced. However. it did not significantly lower hemoglobin Alc(HbAlc) in blood of db/db mice. These result suggest that OCS could be effective on insulin-independent type 2 diabetes.

Tenebrio molitor (Mealworm) Extract Improves Insulin Sensitivity and Alleviates Hyperglycemia in C57BL/Ksj-db/db Mice (C57BL/Ksj-db/db 제 2형 당뇨모델을 이용한 갈색거저리 유충(밀웜) 추출물의 인슐린 감수성 및 혈당개선효과)

  • Kim, Seon Young;Park, Jae Eun;Han, Ji Sook
    • Journal of Life Science
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    • v.29 no.5
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    • pp.570-579
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    • 2019
  • Diabetes is one of the serious chronic metabolic diseases caused by Westernized eating habits, and the goal of diabetes treatment is to keep blood glucose at a normal level and prevent diabetic complications. This study was designed to investigate the anti-diabetic effects of a mealworm (Tenebrio molitor larva) extract (MWE) on hyperglycemia in an animal model with type 2 diabetes. Diabetic C57BL/Ksj-db/db mice were divided into three groups: diabetic control, rosiglitazone, and MWE. The mice supplemented with MWE showed significantly lower blood levels of glucose and glycosylated hemoglobin when compared with the diabetic control mice. The homeostatic index of insulin resistance was significantly lower in mice supplemented with MWE than in diabetic control mice. MWE supplementation significantly stimulated the phosphorylation of insulin receptor substrate-1 and Akt, and activation of phosphatidylinositol 3-kinase in insulin signaling pathway of skeletal muscles. Eventually, MWE increased the expression of the plasma membrane glucose transporter 4 (GLUT4) via PI3K/Akt activation. These findings demonstrate that the increase in plasma membrane GLUT4 expression by MWE promoted the uptake of blood glucose into cells and relieved hyperglycemia in skeletal muscles of diabetic C57BL/Ksj-db/db mice. Therefore, mealworms are expected to prove useful for the prevention and treatment of diabetes, and further studies are needed to improve type 2 diabetes in the future.

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.

Effect of Silk Fibroin Hydrolysate on Adipocyte Metabolism in db/db Mice (실크 피브로인 산 가수분해물이 db/db mice의 지방세포 대사에 미치는 영향)

  • Hong, Seong-Eui;Park, Kum-Ju;Suh, Byung-Sun;Do, Myoung-Sool;Hyun, Chang-Kee
    • Korean Journal of Pharmacognosy
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    • v.33 no.4 s.131
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    • pp.312-318
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    • 2002
  • Effect of the acid hydrolysate of silk fibroin on obesity was investigated in obese(057BL/KsJ-db/db) mice. After 8 weeks feeding of 1%(w/w) or 3%(w/w) fibroin hydrolysate, the extents of reduction in body weight were significantly higher than that of obese control. The weight reduction in female mice was higher than that in male mice. Plasma leptin in male mice increased up to 1.8-fold higher level than obese control by feeding hydrolysate. In case of female mice, however, it rather decreased with increased feeding concentration of hydrolysate. From the results of high glycine and serine contents of peptide fractions contained in fibroin hydrolysate, it was inferred that fibroin peptides might affect xylosyltransferase(XT) activity on chondroitin sulfate synthesis causing to change susceptibility of adipocytes to hormones such as insulin followed by the reduced leptin synthesis in female mice. The result of the higher lipolysis in hydrolysate-fed group than obese control indicated that the reduction in body weight was due to the increased lipolytic activities in male and female mice in common.

Effects of Gamiolnyeo-jeon on Lipid Metabolism and Blood Glucose Level in db/db Mice (가미옥녀전(加味玉女煎)이 db/db 마우스 당뇨(糖尿)모델에서 지질대사(脂質代謝)와 항당뇨(抗糖尿) 효능(效能)에 미치는 영향(影響))

  • Sim, Boo-Yong;Kim, Dong-Hee
    • The Korea Journal of Herbology
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    • v.31 no.2
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    • pp.39-45
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    • 2016
  • Objectives : Abnormal regulation of glucose and impaired lipid metabolism that result from a defective or deficient insulin are the key etiological factor in type 2 diabetes mellitus. The our study investigated the effects of Gamioknyeo-jeon (GO) on blood glucose and lipid metabolism improved by it in db/db mice (a murine model of type 2 diabetes mellitus).Methods : The animals were divided into 3 groups: Normal groups were not-treated C57BL/6 mice; Control groups were treated orally with DW in db/db mice; GO groups were treated orally with GO (200 ㎎/㎏/day) in db/db mice. After mice were treated with GO for 5 weeks, we measured AST, ALT, creatinine, BUN, body weight, food intake, blood glucose, insulin and lipid levels (total cholesterol, HDL cholesterol, and LDL cholesterol and atherogenic index(AI) and cardiac risk factor(CRF).Results : Serum AST, ALT, creatinine, BUN levels were not changed by GO do not show any toxic effects. GO groups were decreased in body weight, food intake and blood glucose level among compared to Control groups. Also, GO groups were found to have atherogenic Index and cardiac risk factor as well as lipid metabolism improvement (total cholesterol and LDL cholesterol decrease). Finally, GO groups were increased the insulin compared to Normal and control groups.Conclusions : We suggest that GO may have the control effects of diabetes mellitus by improving blood glucose control and lipid metabolism.

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.