• Title/Summary/Keyword: db/db-mice

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Design and Synthesis of Oxime Ethers of β-Oxo-γ-phenylbutanoic Acids as PPAR α and -γ Dual Agonists

  • Han, Hee-Oon;Koh, Jong-Sung;Kim, Seung-Hae;Park, Ok-Ku;Kim, Kyoung-Hee;Jeon, Sang-Kweon;Hur, Gwong-Cheung;Yim, Hyeon-Joo;Kim, Geun-Tae
    • Bulletin of the Korean Chemical Society
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    • v.33 no.6
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    • pp.1979-1982
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    • 2012
  • Oxime ethers of ${\beta}$-oxo-${\gamma}$-phenylbutanoic acids were prepared to develop more effective PPAR ${\alpha}$ and ${\gamma}$ dual agonists. Among them, compound 11k exhibited potent $in$ $vitro$ activities with $EC_{50}$ of 2.5 nM and 3.3 nM in PPAR ${\alpha}$ and ${\gamma}$, respectively. It showed better glucose lowering effects than rosiglitazone 1 and improved the lipid profile like plasma triglyceride in db/db mice model.

Antidiabetic Effect of Beta vulgaris Mixture: Regulation of Glycolytic Enzymes and Pancreatic Beta Cells

  • Dae Sik Haam;Dong-Yeop Shin;Hak Yong Lee;Young Mi Park;Byeong-Soo Kim;Myung-Sunny Kim;Hye Jeong Yang;Na-Rae Shin
    • Journal of Food and Nutrition Research
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    • v.10 no.1
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    • pp.32-40
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    • 2022
  • Diabetes is a chronic metabolic disease with a high prevalence worldwide. Beet (Beta vulgaris) is a plant that is widely used in many countries and has various biological activities. In this study, we aimed to evaluate the antidiabetic effect of a B. vulgaris mixture (BM). In the in vitro evaluation, we measured the inhibitory activities of α-amylase and α-glucosidase, performed the oral starch tolerance test (OATT) and oral sucrose tolerance test (OSTT) in Sprague Dawley (SD) rats, and evaluated the clinical symptoms, oral glucose tolerance test (OGTT), number of blood cells, and insulin resistance in db/db mice. BM showed an inhibitory effect against α-amylase and α-glucosidase activity and decreased the blood glucose increased in the OATT and OSTT. In the diabetes mouse model, BM alleviated the general symptoms of diabetes and OGTT results showed a decrease in the increased blood sugar level. Regarding diabetes-related tissue weight, BM decreased the reduced pancreatic weight and showed an effect on diabetes-related factors of blood. Histological analysis indicated that BM decreased insulin concentration, insulin resistance, and insulin secretion ability in serum, and increased insulin concentration in the islets of Langerhans. These results demonstrate that BM has an antidiabetic effect through the regulation of glycolytic enzymes and β cell activity in the pancreas.

Effects of Three Thiazolidinediones on Metabolic Regulation and Cold-Induced Thermogenesis

  • Sohn, Jee Hyung;Kim, Jong In;Jeon, Yong Geun;Park, Jeu;Kim, Jae Bum
    • Molecules and Cells
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    • v.41 no.10
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    • pp.900-908
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    • 2018
  • Insulin resistance is closely associated with metabolic diseases such as type 2 diabetes, dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones (TZDs) have been developed to ameliorate insulin resistance by activation of peroxisome proliferator-activated receptor (PPAR) ${\gamma}$. Although TZDs are synthetic ligands for $PPAR{\gamma}$, metabolic outcomes of each TZD are different. Moreover, there are lack of head-to-head comparative studies among TZDs in the aspect of metabolic outcomes. In this study, we analyzed the effects of three TZDs, including lobeglitazone (Lobe), rosiglitazone (Rosi), and pioglitazone (Pio) on metabolic and thermogenic regulation. In adipocytes, Lobe more potently stimulated adipogenesis and insulin-dependent glucose uptake than Rosi and Pio. In the presence of pro-inflammatory stimuli, Lobe efficiently suppressed expressions of pro-inflammatory genes in macrophages and adipocytes. In obese and diabetic db/db mice, Lobe effectively promoted insulin-stimulated glucose uptake and suppressed pro-inflammatory responses in epididymal white adipose tissue (EAT), leading to improve glucose intolerance. Compared to other two TZDs, Lobe enhanced beige adipocyte formation and thermogenic gene expression in inguinal white adipose tissue (IAT) of lean mice, which would be attributable to cold-induced thermogenesis. Collectively, these comparison data suggest that Lobe could relieve insulin resistance and enhance thermogenesis at low-concentration conditions where Rosi and Pio are less effective.

Effects of herbal mixture on blood glucose and lipid metabolism in type 2 diabetic mellitus mouse (천연물 복합제가 제 2형 당뇨 마우스에서 혈당 및 지질대사에 미치는 영향)

  • Seo, Dong-hyo;Joo, In-Hwan;Kim, Dong-Hee
    • Journal of Haehwa Medicine
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    • v.29 no.2
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    • pp.22-29
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    • 2020
  • Objectives: This study aims to investigate the effects of diabetes mellitus care mixture (DCM) on blood glucose and lipid metabolism in type 2 diabetic mellitus mice. DCM consisted of lagerstroemia speciose, allium hookeri, momordica charantia, amaranthus tricolor, and boesenbergia rotunda, which have been proven to have antidiabetic properties. Methods: In this study, we researched the effects of DCM in type 2 diabetic mellitus mice. C57BLKS/J mouse groups had no treatment, db/db mouse randomly assigned to 2 groups, and treated with distilled water and DCM (200 mg/kg/day). Blood glucose levels and body weight were checked every week. After 4 weeks of treatment, liver function indicators (AST, ALT, and LDH) and lipid metabolites (triglyceride, total cholesterol, LDL-cholesterol, HDL-cholesterol) were measured with a biochemistry analyzer. Diabetic factors (insulin, resistin, and leptin) were measured with ELISA. Results: DCM was decreased blood glucose, diabetic factors, liver function indicators, triglyceride, total cholesterol, and LDL-cholesterol significantly. Also, HDL-cholesterol was significantly increased in DCM group. The bodyweight of DCM group decreased but, no significant difference with the control group. DCM may have the potential to improved diabetes mellitus by regulating blood glucose levels and diabetic factors. Also protecting from diabetic complications by adjusting liver function indicators and lipid metabolites. Conclusions: These results suggest that DCM to be used as an oriental medicine for diabetes, the results of clinical trials are needed.

The influence of diabetes mellitus on periodontal tissues: a pilot study

  • Um, Yoo-Jung;Jung, Ui-Won;Kim, Chang-Sung;Bak, Eun-Jung;Cha, Jeong-Heon;Yoo, Yun-Jung;Choi, Seong-Ho
    • Journal of Periodontal and Implant Science
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    • v.40 no.2
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    • pp.49-55
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    • 2010
  • Purpose: The purpose of this study was to preliminarily evaluate the influence of diabetes mellitus (DM) on periodontal tissue without establishment of periodontitis. Methods: Seven-week-old db/db mice were used for the diabetic experimental group and systematically healthy mice of the same age were used as controls. After 1 week of acclimatization, the animals were sacrificed for hard and soft tissue evaluation. The pattern of bone destruction was evaluated by stereomicroscope evaluation with alizarin red staining and radiographic evaluation by microscopic computerized tomography images. Histological evaluation was performed with hematoxylin and eosin stain for evaluation of soft tissue changes. Results: In both stereomicroscope evaluation and radiograph image analysis, aggressive form of bone destruction was observed in diabetic animals when compared to the systematically healthy controls. In histological evaluation, apical migration of junctional epithelium with slight inflammatory cell infiltration was observed with disarrangement of connective tissue fibers. Conclusions: Within the limits of this study, diabetic animals presented distortion in periodontal attachment and an aggressive bone loss pattern when compared to the healthy controls, suggesting that DM has an independent effect on periodontal tissue destruction irrespective of the presence or absence of periodontal disease.

Review on Amorfrutin of Licorice for Type2 Diabetes Mellitus (감초의 amorfrutin성분과 당뇨 치료 효과에 대한 고찰)

  • Han, Juhee;Heo, Hyemin;Jeong, Minjeong;Kim, Hongjun;Jang, Insoo
    • The Journal of Internal Korean Medicine
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    • v.41 no.6
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    • pp.1078-1088
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    • 2020
  • Objective: The purpose of this study was to investigate the effect of amorfrutin of licorice for Type2 diabetes mellitus. Method: The PubMed, CNKI, Wanfang, OASIS, NDSL, J-STAGE, and CiNii databases were searched from the beginning of the search to September 20, 2020, with no limits on language. Extractions and selections from the literature were made by two authors. The study included in vivo experiments with amorfrutins in high-fat diet-induced obesity C57BL/6 mice and leptin receptor-deficient db/db mice and in silico studies. Results & Conclusion: Four studies were finally selected. We confirmed that amorfrutin treatment considerably improved insulin sensitivity and glucose tolerance and reduced plasma insulin and glucose. Amorfrutins bind to and selectively activate Peroxisome Proliferator-Activated Receptor Gamma (PPARγ), which plays an important role in glucose metabolism. Amorfrutins also strongly bind to the glucagon receptor (GCGR) and work as antagonist. Using the amorfrutins from licorice could therefore be helpful in treating type2 diabetes mellitus.

Brown preadipocyte transplantation locally ameliorates obesity

  • Takaya, Kento;Matsuda, Naruhito;Asou, Toru;Kishi, Kazuo
    • Archives of Plastic Surgery
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    • v.48 no.4
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    • pp.440-447
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    • 2021
  • Background Brown adipose tissue (BAT) is a potential target for anti-obesity treatments. Previous studies have shown that BAT activation causes an acute metabolic boost and reduces adiposity. Furthermore, BAT and BAT-derived cell transplantation reportedly help treat obesity by regulating glucose and fatty acid metabolism. However, since BAT transplantation leads to whole-body weight loss, we speculated that earlier approaches cause a generalized and unnecessary fat tissue loss, including in breast and hip tissues. Methods We transplanted white adipose tissue-derived or BAT-derived preadipocytes prepared from C57BL/6 mice into one side of the inguinal fat pads of an obese mouse model (db/db mice) to examine whether it would cause fat loss at the peri-transplant site (n=5 each). The same volume of phosphate-buffered saline was injected as a control on the other side. Six weeks after transplantation, the inguinal fat pad was excised and weighed. We also measured the concentrations of glucose, triglycerides, fatty acids, and total cholesterol in the peripheral blood. Results BAT-derived preadipocytes showed abundant mitochondria and high levels of mitochondrial membrane uncoupling protein 1 expression, both in vivo and in vitro, with a remarkable reduction in weight of the inguinal fat pad after transplantation (0.17±0.12 g, P=0.043). Only free fatty acid levels tended to decrease in the BAT-transplanted group, but the difference was not significant (P=0.11). Conclusions Our results suggest that brown adipocytes drive fat degradation around the transplantation site. Thus, local transplantation of BAT-derived preadipocytes may be useful for treating obesity, as well as in cosmetic treatments.

Hypolipidemic effect of Salicornia herbacea in animal model of type 2 diabetes mellitus

  • Hwang, Ji-Yeon;Lee, Soo-Kyung;Jo, Ja-Rim;Kim, Mi-Eun;So, Hyun-Ah;Cho, Chang-Woo;Seo, Young-Wan;Kim, Jung-In
    • Nutrition Research and Practice
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    • v.1 no.4
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    • pp.371-375
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    • 2007
  • To control blood glucose level as close to normal is a major goal of treatment of diabetes mellitus. Hyperglycemia and hyperlipidemia are the major risk factors for cardiovascular complications, the major cause of immature death among the patients with type 2 diabetes. The purpose of this study is to determine the hypoglycemic and hypolipidemic effects of Salicornia herbacea in animal model of type 2 diabetes and to investigate the possible mechanisms for the beneficial effects of S. herbacea. S. herbacea was extracted with 70% ethanol and desalted with 100% ethanol. Three week-old db/db mice (C57BL/KsJ, n=16) were fed AIN-93G semipurified diet or diet containing 1% desalted ethanol extract of S. herbacea for 6 weeks after 1 week of adaptation. Fasting plasma glucose, triglyceride, and total cholesterol were measured by enzymatic methods and blood glycated hemoglobin ($HbA_{1C}$) by the chromatographic method. Body weight and food intake of S. herbacea group were not significantly different from those of the control group. Fasting plasma glucose and blood glycated hemoglobin levels tended to be lowered by S. herbacea treatment. Consumption of S. herbacea extract significantly decreased plasma triglyceride and cholesterol levels (p<0.05). The inhibition of S. herbacea extract against yeast ${\alpha}$-glucosidase was 31.9% of that of acarbose at the concentration of 0.5 mg/mL in vitro. The inhibitory activity of ethanol extract of S. herbacea against porcine pancreatic lipase was 59.0% of that of orlistat at the concentration of 0.25 mg/mL in vitro. Thus, these results suggest that S. herbacea could be effective in controlling hyperlipidemia by inhibition of pancreatic lipase in animal model of type 2 diabetes.

Effects of Allium Hookeri on Glucose Metabolism in Type II Diabetic Mice (삼채(Allium Hookeri)의 급여가 당뇨마우스의 당질 대사에 미치는 영향)

  • Kim, Nam-Seok;Choi, Bong-Kyoum;Lee, Seon-Hye;Jang, Hwan-Hee;Kim, Jung-Bong;Kim, Haeng-Ran;Kim, Dae Keun;Kim, You-Suk;Yang, Jae-Heon;Kim, Hyun-Ju;Lee, Sung-Hyen
    • Korean Journal of Pharmacognosy
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    • v.46 no.1
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    • pp.78-83
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    • 2015
  • This study was conducted to verify the potential of Allium hookeri to control glucose metabolism in a diabetes model. We fed the experimental diets (AL, AR, Dex) supplemented with the powder of leaf, root, or dextrin as a positive control, respectively at 3% of diet to the diabetic mice (C57BLKS/J, db/db) for 8 weeks. Control mice were fed with the diet supplemented with cornstarch (Cont) at 3% level of diet. At 8th week of feeding the diets, we measured body weight, blood glucose, HbA1c, and plasma insulin levels and conducted an oral glucose tolerance test (OGTT) and staining insulin immunoreactive cells in islets of pancreas. AL group treated with the leaf of A. hookeri showed significantly lower blood glucose and HbA1c levels, higher plasma insulin levels, and increased density of insulin immunoreactive cells compared with the Cont group. During the OGTT, AL group showed lower blood glucose levels than the Cont group for 120 min. Based on these results, leaf of A. hookeri is considered to be effective in improving glucose tolerance by partially affecting insulin secretion and it may be used to prevent and treat diabetic disease.

Cilostazol Decreases Ethanol-Mediated TNFalpha Expression in RAW264.7 Murine Macrophage and in Liver from Binge Drinking Mice

  • Lee, Youn-Ju;Eun, Jong-Ryeol
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.2
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    • pp.131-138
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    • 2012
  • Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor ${\alpha}$ (TNF${\alpha}$) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNF${\alpha}$ production in vitro and $in$ $vivo$, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNF${\alpha}$ mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP- activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNF${\alpha}$ production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The $in$ $vivo$ effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNF${\alpha}$ mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNF${\alpha}$ production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNF${\alpha}$ production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNF${\alpha}$ production by cilostazol.