• Title/Summary/Keyword: db/db-mice

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Wnt/β-catenin signaling activator restores hair regeneration suppressed by diabetes mellitus

  • Yeong Chan, Ryu;You-rin, Kim;Jiyeon, Park;Sehee, Choi;Geon-Uk, Kim ;Eunhwan, Kim;Yumi, Hwang;Heejene, Kim;Soon Sun, Bak;Jin Eun, Lee;Young Kwan, Sung;Gyoonhee, Han;Soung-Hoon, Lee;Kang-Yell, Choi
    • BMB Reports
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    • v.55 no.11
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    • pp.559-564
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    • 2022
  • Diabetes mellitus is one of the most prevalent diseases in modern society. Many complicationssuch as hepatic cirrhosis, neuropathy, cardiac infarction, and so on are associated with diabetes. Although a relationship between diabetes and hair loss has been recently reported, the treatment of diabetic hair loss by Wnt/β-catenin activators has not been achieved yet. In this study, we found that the depilation-induced anagen phase was delayed in both db/db mice and high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice. In diabetic mice, both hair regrowth and wound-induced hair follicle neogenesis (WIHN) were reduced because of suppression of Wnt/β-catenin signaling and decreased proliferation of hair follicle cells. We identified that KY19382, a small molecule that activates Wnt/β-catenin signaling, restored the capabilities of regrowth and WIHN in diabetic mice. The Wnt/β-catenin signaling activator also increased the length of the human hair follicle which was decreased under high glucose culture conditions. Overall, the diabetic condition reduced both hair regrowth and regeneration with suppression of the Wnt/β-catenin signaling pathway. Consequently, the usage of Wnt/β-catenin signaling activators could be a potential strategy to treat diabetes-induced alopecia patients.

Anti-diabetic Effects of Barnyard Millet Miryang 3 [Echinochloa esculenta (A. Braun)] Grains on Blood Glucose in C57BL/KsJ-db/db Mice (식용피 밀양3호[Echinochloa esculenta (A. Braun)] 에탄올 추출물의 당뇨모델 마우스에 대 한 항당뇨 활성)

  • Kwon, Gi Hyun;Jun, Do Youn;Lee, Ji Young;Park, Jueun;Woo, Mi Hee;Yoon, Young Ho;Ko, Jee Youn;Oh, In-Seok;Kim, Young Ho
    • Journal of Life Science
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    • v.25 no.11
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    • pp.1265-1272
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    • 2015
  • Barnyard millet Miryang 3 [Echinochloa esculenta (A. Braun)] grains have recently been acknowledged for beneficial health properties due to phenolic ingredients and dietary fiber. This study has been conducted on the anti-diabetic activity of barnyard millet Miryang 3 which shows the strongest anti-inflammatory activity among barnyard millet inhabiting in South Korea. When 80% ethanol (EtOH) extract of barnyard millet Miryang 3 grains were orally administered into db/db diabetic mice for 8 weeks (600 mg/kg/day), the glucose level in blood following fasting appeared to be improved compared to the control group. The results of glucose tolerance test and blood lipid profile assay were similar to those of the metformin-administered positive control group. In addition, the level of body weight increase (8.54±2.24) was lower than the level of metformin-administered group (10.36±3.15); however, there was no subtle difference with negative and positive control groups in terms of food efficiency rates. In addition, total cholesterol levels of the 80% EtOH extract-administered group (160.7±7.6) were significantly reduced compared to the diabetic control group (229.3±47.8) and metformin-administered group (176.0±25.6). Consequently, these results show that barnyard millet grains alleviates many of the diabetic symptoms in vivo non-insulin-dependent diabetes mellitus, and suggest that barnyard millet grains can be applicable in developing new functional food materials.

Antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes mellitus

  • Lee, Young-Min;Gweon, Oh-Cheon;Seo, Yeong-Ju;Im, Ji-Eun;Kang, Min-Jung;Kim, Myo-Jeong;Kim, Jung-In
    • Nutrition Research and Practice
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    • v.3 no.2
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    • pp.156-161
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    • 2009
  • Hyperglycemia in the diabetic state increases oxidative stress and antioxidant therapy can be strongly correlated with decreased risks for diabetic complications. The purpose of this study is to determine antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes. The antioxidant activity of garlic and aged black garlic was measured as the activity in scavenging free radicals by the trolox equivalent antioxidant capacity (TEAC) assay. Three week-old db/db mice were fed AIN-93G diet or diet containing 5% freeze-dried garlic or aged black garlic for 7 weeks after 1 week of adaptation. Hepatic levels of lipid peroxides and activities of antioxidant enzymes were measured. TEAC values of garlic and aged black garlic were $13.3{\pm}0.5$ and $59.2{\pm}0.8{\mu}mol/g$ wet weight, respectively. Consumption of aged black garlic significantly decreased hepatic thiobarbituric acid reactive substances (TBARS) level compared with the garlic group which showed lower TBARS level than control group (p<0.05). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of garlic and aged black garlic group were significantly elevated compared to the control group. Catalase (CAT) activity of aged black garlic group was increased compared with the control group. These results show that aged black garlic exerts stronger antioxidant activity than garlic in vitro and in vivo, suggesting garlic and aged black garlic, to a greater extent, could be useful in preventing diabetic complications.

Development of High Functional Collagen Peptide Materials using Skate Skins (홍어껍질을 이용한 고기능성 콜라겐 펩타이드 소재 개발)

  • Baek, Jang-Mi;Kang, Keon-Hee;Kim, Sang-Ho;Noh, Jeong-Sook;Jeong, Kap-Seop
    • Journal of Environmental Science International
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    • v.25 no.4
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    • pp.579-588
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    • 2016
  • The aim of this study was to investigate and development collagen peptide materials from skate skin. Protein and fat content of collagen peptide showed about 95% and 0.1%, respectively. Average molecular weight of collagen peptide was measured as 1,015. In the analysis of amino acid, glycine and hydroxy proline content in collagen peptide was 19.32% and 16.25%, respectively, showing a typical characteristics of the collagen peptide. In obese db/db mice ingested 500 mg/day of collagen peptide for 18 days, the amounts of food and water intake were decreased considerably, contents of triglyceride, total cholesterol were decreased significantly in white adipose tissue of db/db mice. The final yield of collagen peptide was 17.23% in the optimized process for mass production. These results indicate that collagen peptide from skate skin may serve as candidates of fat reduction in adipose tissue and could be used as functional food and cosmetic ingredients.

Antioxidative and Anti-diabetic Activity of C3GHi, Novel Black Rice Breed (Cyanidine-3-glucoside (C3G) 색소의 함유량이 증대된 쌀 신품종(C3GHi)의 항산화 및 항당뇨 활성)

  • Kim, Hwa-Young;Kim, Joong-Hark;Lee, Sung-Ae;Ryu, Su-Noh;Han, Sang-Jun;Hong, Seong-Gil
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.55 no.1
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    • pp.38-46
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    • 2010
  • C3GHi, a novel black rice variety developed by conventional breeding has more high contents of cyanidine-3-glucoside (C3G) and a more strong antioxidant than normal black rice. In this study, we investigate the antioxidative potential and anti-diabetic activity of C3GHi and extract of it for the purpose of development of functional materials or replacement meal for diabetic patients. Using in vitro antioxidative activity assay system such as DPPH radical quenching assay, superoxide anion radical scavenging assay, inhibition of lipid peroxidation and DNA breakage assay, C3GHi extract was observed to have more high antioxidative activity than normal black rice breed. The glycemic index of a freeze dried powder of C3GHi brown rice showed $43.7\pm18.8$, which belonged to low GI food (GI of 55 or less). Using in vivo diabetic model such as db/db mice model and streptozotocininduced diabetic model, C3GHi rice extract decrease blood glucose level and inhibit oxidative stress in blood. From the results, we think that the C3GHi varieties have a potential for the functional materials or ingredient of meal replacement for diabetic patients.

Hypolipidemic and Anti-oxidant Effects of Chunghyl Plus in Type II Diabetic Mice Model (제2형 당뇨 마우스 모델에서 청혈플러스의 항고지혈 및 항산화효과)

  • Choi, Koh Eun;Seol, In Chan;Kim, Yoon Sik;Cho, Hyun Kyoung;Yoo, Ho Ryong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.30 no.3
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    • pp.164-176
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    • 2016
  • This study was perfomed to investigate the effects of Chunghyul-plus(CHP) on oxidative damage and hyperlipidemia in db/db mouse. After treatment with CHP, safety in cytotoxicity, heavy metal toxicity, production of reactive oxygen species(ROS), nitric oxide (N0) and proinflammatory cytokine IL-Ib, TNF-a, IL-6 in RAW 264.7 cells. Serum total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, insulin, GLP-1, glucose, food intake, body weight, organ weight, AST, ALT, ALP, BUN, creatine and histologic change of liver and aorta were measured in db/db mouse after oral administration of CHP. CHP showed safety in cytotoxicity and toxicity of liver and kidney for logn time administration. CHP increased the DPPH and ABTS radical scavenging activity. CHP showed significant inhibitory effect on reactive oxygen species (ROS), and showed inhibitory effect on nitiric oxide(NO) compared to control group. CHP decreased cytokine IL-6 production significantly, and decreased IL-1β and TNF-α compared to control group. CHP decreased body and organ weitht, intake food, and glucose levels compared to control group. CHP decreased total cholesterol and triglyceride significantly, and decreased LDL-cholesterol levels and increased HDL-cholesterol levels compared to control group. CHP decreased atherogenic index and cardiac risk factor significantly. CHP increased serum insulin and GLP-1 compared to control group. In histologic examination, lipophagy in the liver and aorta decreased in CHP treated mice and the cell was regular and boundary of vessel wall was clear compared to control group. These results suggest that CHP is effective in antioxidation activity and treatment and prevention of hyperlipidemia, atherosclerosis, diabetes, ischemic heart disease, stroke and other cardiocerebrovascular disease.

The Hypoglycemic Effect of Saururus chinensis Baill in Animal Models of Diabetes Mellitus

  • Joo, Hee-Jeong;Kang, Ming-Jung;Seo, Tae-Jin;Kim, Hyun-A;Yoo, Sung-Ja;Lee, Soo-Kyung;Lim, Hwa-Jae;Byun, Boo-Hyeong;Kim, Jung-In
    • Food Science and Biotechnology
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    • v.15 no.3
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    • pp.413-417
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    • 2006
  • The purpose of this study was to investigate the hypoglycemic effect of Saururus chinensis Baill in vitro and in vivo. Methanol extract of S. chinensis Baill inhibited yeast ${\alpha}$-glucosidase activity by 49.8%, which was twice as strong as that of acarbose at a concentration of 0.5 mg/mL in vitro. The effect of S. chinensis Baill methanol extract on the postprandial increase in blood glucose levels was studied in streptozotocin-induced diabetic rats using a carbohydrate load test. Oral administration of S. chinensis Baill extract (500 mg/kg) significantly decreased incremental blood glucose levels at 60 and 90 min (p<0.05) after oral ingestion of starch (1 g/kg). The area under the glucose response curve of the S. chinensis Baill group was significantly decreased compared to that of the control group (p<0.05). The effect of prolonged feeding of S. chinensis Baill was studied in an animal model of type 2 diabetes. Three-week-old db/db mice were fed an AIN-93G diet or a diet containing 0.5% S. chinensis Baill extract for 7 weeks after 1 week of adaptation. Plasma glucose, insulin, and blood glycated hemoglobin levels of the mice fed S. chinensis Baill extract were significantly lower than those of the control group (p<0.05). Therefore, we conclude that S. chinensis Baill is effective in controlling hyperglycemia in animal models of diabetes mellitus.

Compound K attenuates hyperglycemia by enhancing glucagon-like peptide-1 secretion through activating TGR5 via the remodeling of gut microbiota and bile acid metabolism

  • Tian, Fengyuan;Huang, Shuo;Xu, Wangda;Chen, Lan;Su, Jianming;Ni, Haixiang;Feng, Xiaohong;Chen, Jie;Wang, Xi;Huang, Qi
    • Journal of Ginseng Research
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    • v.46 no.6
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    • pp.780-789
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    • 2022
  • Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.

The Effect of Metformin Treatment on CRBP-I Level and Cancer Development in the Liver of HBx Transgenic Mice

  • Kim, Jo-Heon;Alam, Morshedul;Park, Doek Bae;Cho, Moonjae;Lee, Seung-Hong;Jeon, You-Jin;Yu, Dae-Yeul;Kim, Tae Du;Kim, Ha Young;Cho, Chung Gu;Lee, Dae Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.5
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    • pp.455-461
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    • 2013
  • Retinoids regulate not only various cell functions including proliferation and differentiation but also glucose and lipid metabolism. After we observed a marked up-regulation of cellular retinol-binding protein-I (CRBP-I) in the liver of hepatitis B virus x antigen (HBx)-transgenic (HBx Tg) mice which are prone to hepatocellular carcinoma (HCC) and fatty liver, we aimed to evaluate retinoid pathway, including genes for the retinoid physiology, CRBP-I protein expression, and retinoid levels, in the liver of HBx Tg mice. We also assessed the effect of chronic metformin treatment on HCC development in the mice. Many genes involved in hepatic retinoid physiology, including CRBP-I, were altered and the tissue levels of retinol and all-trans retinoic acid (ATRA) were elevated in the liver of HBx Tg mice compared to those of wild type (WT) control mice. CRBP-I protein expression in liver, but not in white adipose tissue, of HBx Tg mice was significantly elevated compared to WT control mice while CRBP-I protein expressions in the liver and WAT of high-fat fed obese and db/db mice were comparable to WT control mice. Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level. In conclusion, hepatic CRBP-I level was markedly up-regulated in HCC-prone HBx Tg mice and neither hepatic CRBP-I nor the development of HCC was suppressed by metformin treatment.

HD047703, a New Promising Anti-Diabetic Drug Candidate: In Vivo Preclinical Studies

  • Kim, SoRa;Kim, Dae Hoon;Kim, Young-Seok;Ha, Tae-Young;Yang, Jin;Park, Soo Hyun;Jeong, Kwang Won;Rhee, Jae-Keol
    • Biomolecules & Therapeutics
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    • v.22 no.5
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    • pp.400-405
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    • 2014
  • G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic b-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic ${\beta}$-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.