• Journal of Microbiology and Biotechnology
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• v.19 no.10
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• pp.1109-1121
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• 2009

In an attempt to discover novel biomarker proteins in type 2 diabetes prognosis, we investigated the influence of hypoglycemic extracellular polysaccharides (EPS) obtained from the macrofungus Tremella fuciformis on the differential levels of plasma proteins in ob/ob mice using two-dimensional gel electrophoresis (2-DE). The 2-DE analysis demonstrated that 92 spots from about 900 visualized spots were differentially regulated, of which 40 spots were identified as principal diabetes-associated proteins. By comparing control with EPS-fed mice, we found that at least six proteins were significantly altered in ob/ob mice, including Apo A-I, IV, C-III, E, retinol-binding protein 4, and transferrin, and their levels were interestingly normalized after EPS treatment. Western blot analysis revealed that the altered levels of the two regulatory molecules highlighted in diabetes and obesity (e.g., resistin and adiponectin) were also normalized in response to EPS. The Mouse Diabetes PCR Array profiles showed that the expression of 84 genes related to the onset, development, and progression of diabetes were significantly downregulated in liver, adipocyte, and muscle of ob/ob mice. EPS might act as a potent regulator of gene expression for a wide variety of genes in ob/ob mice, particularly in obesity, insulin resistance, and complications from diabetes mellitus.

• Advances in Traditional Medicine
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• v.9 no.1
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• pp.20-38
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• 2009

The objectives of this study were to determine the effect of herb formula HDDM, a modification of Huangdan decoction that has been shown to be effective in the treatment of glomerulonephritis and chronic renal failure, on the blood glucose levels in multiple low doses (MLD; 50 mg/kg for five consecutive days) of streptozotocin (STZ)-treated female B6C3F1 mice. Initial studies were performed to compare diabetes induction in five strains (e.g., B6C3F1, NOD, CD-1, C3H/HeN and C57BL/6) of mice by MLD-STZ, and immune changes following the treatment. The results suggested that the order of susceptibility to diabetes induction was NOD $\approx$ CD-1 > B6C3F1 $\approx$ C3H > C57BL/6. Furthermore, STZ modulation of T cell development, differentiation and activation might play a role in diabetes induction by MLD-STZ treatment. MLD-STZ-induced diabetes in female B6C3F1 mice was moderate, which allowed the evaluation of drug-induced protection or exacerbation of diabetes to be performed. As such, modulation of blood glucose by HDDM, which consisted of Da Huang (Radix Et Rhizoma Rhei), Huang Qi (Radix Astragali Seu Hedysari), Dan Shen (Radix Salviae Miltiorrhizae), Yin Yang Huo (Herba Epimedii), Yi Yi Ren (Semen Coicis or Coix lacryma-jobi), Mai Dong (Radix Ophiopogonis) and Shan Zhu Yu (Fructus Corni), was evaluated in MLD-STZ-treated female B6C3F1 mice. The results suggested that HDDM could lower the blood glucose levels, but it had no immunomodulatory activities. Additionally, HDDM-treated mice exhibited improved glucose tolerance. In conclusion, these studies have suggested that MLD-STZ-induced diabetes in female B6C3F1 mice is a useful model to evaluate drug modulation of diabetes, and that the herb formula HDDM possesses anti-diabetic effects.

• Nutrition Research and Practice
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• v.13 no.5
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• pp.377-383
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• 2019

BACKGROUND/OBJECTIVES: Hyperglycemia-induced hepatic damage has been recognized as one of the major cause of complications in diabetes. Hepatic complications are associated with inflammation and oxidative stress in diabetes. In this study, we investigated the hypothesis that gamma-tocopherol (GT) supplementation ameliorates NLRP3 inflammasome associated hepatic inflammation in diabetes. MATERIALS/METHODS: Diabetes was induced by the intraperitoneal injection of alloxan (150 mg/kg. BW) in ICR mice. All mice were fed with a control diet (AIN-76A). After diabetes was induced (fasting glucose level ${\geq}250mg/dL$), the mice were treated with tocopherol-stripped corn oil or GT-supplemented (35 mg/kg) corn oil, respectively, by gavage for 2 weeks. RESULTS: GT supplementation reduced fasting blood glucose levels in diabetic mice relative to non-treated diabetic mice. Moreover, GT supplementation ameliorated hyperglycemia-induced hepatic damage by regulation of NOD-like receptor protein 3 (NLRP3)-inflammasome associated inflammation represented by NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, caspase-1, nuclear $factor-{\kappa}B$ pathway as well as oxidative stress demonstrated by nuclear factor erythroid 2-related factor 2, NAD(P)H dehydrogenase quinone 1, catalase and glutathione-dependent peroxidase in diabetic mice. CONCLUSION: The findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.

• Journal of the Korea Society of Computer and Information
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• v.21 no.7
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• pp.61-66
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• 2016

The frequency of obesity has risen dramatically in recent years but only few safe and effective drugs are currently available. In addition, obesity can induce type 2 diabetes (T2DM), hyperlipidemia and fatty liver disease. Recently, protective effect of purslane extract (PE) on obesity has been reported, but little is known about the role and mechanism of PE in obesity. This study aimed to evaluate the effect of PE on obesity and diabetes in obese mice. In addition, the effect of PE was compared with anti-obesity and diabetes drugs. High-fat diet (HFD)-induced obese mice were treated for 8 weeks with drugs as follows: PE, orlistat, metformin, voglibose or pioglitazone. While PE mixed with normal diet did not have any effects on BW in non-obese mice, PE mixed with HFD significantly reduced BW gain, insulin resistance, and glucose intolerance, without affecting food intake and appetite in obese mice. The effect was comparable to the effects of anti-obesity and diabetes drugs. Furthermore, PE significantly increased the activity of hepatocellular anti-oxidant enzymes, leading to protection of liver from oxidative stress in obese mice. These results suggest that PE treatment may be a useful tool for preventing obesity and complication of obesity.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.423-426
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• 2013

Females are more often affected by constipation than males, especially during pregnancy, which is related to the menstrual cycle. Although still controversial, alterations of progesterone and estrogen may be responsible. Therefore, this study was conducted in order to determine whether the female sex steroid hormone itself is responsible for development of constipation in both female and male mice. Administration of estrogen resulted in a decrease in weight of accumulated feces on days 2, 3, 4, and 5 in male mice and on day 5 in female mice, compared with the control group, but progesterone administration did not. Administration of estrogen resulted in a decrease in gastrointestinal movement, compared to normal; however, no significant change was observed by administration of progesterone. In conclusion, estrogen, rather than progesterone, may be a detrimental factor of constipation via decreased bowel movement in mice.

• Journal of Ginseng Research
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• v.36 no.2
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• pp.153-160
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• 2012

Panax ginseng has long been used as a traditional herbal medicine. More recently, it has received attention for its anti-diabetic and anti-obesity effects in humans and in animal models of type 2 diabetes. In the present study, we tested the hypoglycemic effects of ginseng berry extract in beta-cell-deficient mice and investigated the mechanisms involved. Red (ripe) and green (unripe) berry extracts were prepared and administered orally (100 or 200 mg/kg body weight) to streptozotocin-induced diabetic mice daily for 10 wk. The body weight was measured daily, and the nonfasting blood glucose levels were measured after 5 and 10 wk after administration. Glucose tolerance tests were performed, and the serum insulin levels were measured. The proliferation of beta-cells was measured in vitro. The administration of red or green ginseng berry extract significantly reduced the blood glucose levels and improved the glucose tolerance in beta-cell deficient mice, with the higher doses resulting in better effects. Glucose-stimulated insulin secretion was significantly increased in berry extract-treated mice compared with streptozotocin-induced diabetic control mice. Treatment with ginseng berry extract increased beta-cell proliferation in vitro. Both red berry and green berry extracts improved glycemic control in streptozotocin-induced diabetic mice and increased insulin secretion, possibly due to increased beta-cell proliferation. These results suggest that ginseng berry extracts might have beneficial effects on beta-cell regeneration.

• Clinical and Experimental Reproductive Medicine
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• v.47 no.1
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• pp.20-33
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• 2020

Objective: The differences between type 1 and type 2 diabetes mellitus (T1DM and T2DM) in terms of their adverse effects on male reproductive parameters have never been elucidated. This study aimed to distinguish between the effects of the DM types in mice treated with multiple low doses of streptozotocin (STZ) to mimic human T1DM and coadministered a high-fat diet (HFD) to mimic human T2DM. Methods: The T1DM mice were intraperitoneally injected with STZ (40 mg/kg body weight) for 5 days. The T2DM mice received an HFD for 14 days prior to STZ injection (85 mg/kg body weight), followed by continuous feeding of an HFD. Male reproductive parameters were evaluated. Results: The reproductive organs of the DM mice weighed significantly less than those of controls, and the seminal vesicles plus prostates of the T1DM mice weighed less than those of the T2DM mice. Increased sperm abnormalities and incomplete DNA packaging were observed in the DM groups. Sperm concentration and the proportion of normal sperm were significantly lower in the T1DM group. The seminiferous histopathology of DM mice was classified into seven types. The penises of the DM mice were smaller than those of the controls; however, tunica albuginea thickness and the amount of penile collagen fibers were increased in these mice. Round germ cells were abundant in the epididymal lumens of the mice with DM. Conclusion: T1DM adversely affected reproductive parameters to a greater extent than T2DM.

• Herbal Formula Science
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• v.21 no.2
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• pp.110-120
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• 2013

Objectives : The object of this study was to observe the pharmacological effects of Yookmijihwang-tang-gamibang (Liuweidihuang-tang-jiaweifang, YGB) consisted of 17 types of herbs has been traditionally used in Korean medicine for treating various disorders in clinics, aqueous extracts on the genetically obese and type II diabetic C57BL/6JHam-ob/ob(ob/ob) mice. Methods :Three different dosages of YGB were orally administered, once a day for 28 days to ob/ob mice with ob/ob control and C57BL/6JJms normoglycemic intact mice. Four weeks after treatments of YGB: the changes on the body weight, food consumption, blood glucose levels, leptin and adiponectin contents were observed for monitoring the antiobese and antidiabetic effects of YGB. The effects were compared to those of CLA(conjugated linoleic acid) which improve type II diabetes and inhibit related obesity. Results : After end of 28 days of continuous treatments, ob/ob control showed increases of adipocyte hypertrophy, vasodilated atrophic glomerulus which were detected with marked hyperplasia of pancreatic islets, insulin and glucagon producing cells. These obese and related type II diabetes induced in ob/ob mice were markedly and significantly inhibited by 28 days of continuous treatment of three dosages of YGB. The YGB 50mg/kg showed similar favorable effects on the diabetes and related diabetic complications as compared with CLA 750mg/kg in ob/ob mice of the present study. Conclusions : The results obtained in this study suggest that over 25mg/kg of YGB extracts favorably retarded the obese and type II diabetes in genetically obese and type II diabetic ob/ob mice.

• Proceedings of the KSAR Conference
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• 2001.03a
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• pp.47-47
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• 2001

The neuropeptide vasopressin (VP) is a nine- amino acid hormone synthesized as preprohormone in the cell bodies of hypothalamic magnocellular neurons. The tumor in magnocellular neurons of the hypothalamus is associated with disfunctions of the cell bodies, leading to the diabetes insipidus. In order to study with the diabetes insipidus caused by a defect in VP synthesis and its secretion, we have produced the transgenic mice regulated by vasopressin promoter inserted to SV40 T antigen coding sequence (pVPSV.IGR2.1). One transgenic line expressing high levels of SV40 T antigen was propagated. The founder and all transgene positive adult animals have appeared with shorten mortality or apparent phenotypic abnormalities, including immune complex disease, and eventually die between 4 and 8 months of age. The mRNA and protein of SV40T antigen transgene were detected in brain of fetus as well as in brain, spleen, lung and lymph node in moribund at the age of 20 weeks. Histological analysis of transgenic mice showed that tumor developed in brain similar to primitive neuroectodermal tumors (PNET) in man. We also detected lymphomas in spleen and lymph node, and consequent tumor formation in various tissues of the transgenic mice. In pVPSV.IGR2.1, 21% mice showed brain tumor (PNET) at 5 weeks and 100% mice showed brain tumor after 15 weeks. In addition, Expression of apoptosis related genes (Bcl-28 & Bax) was increased over their age in mice with PNET as compared to control mice. Apoptosis related gene expression might be deregulated in mice with brain tumor. However, transgenic mice were not developed with the diabetes insipidus. These mice represent the first disease model to exhibit primitive neuroectodermal tumor in brain, as well as a unique model system for exploring the cellular pathogenesis of lymphomas.

• Food Science of Animal Resources
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• v.36 no.2
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• pp.170-177
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• 2016

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. CLA has been reported to be able to reduce body fat. In this study, we investigated the antidiabetic effect of fermented milk (FM) containing CLA on type II diabetes db/db mice. Mice were treated with 0.2% low FM, 0.6% high FM, or Glimepiride (GLM) for 6 wk. Our results revealed that the body weight and the levels of fasting blood glucose, serum insulin, and leptin were significantly decreased in FM fed mice compared to db/db mice. Oral glucose tolerance and insulin tolerance were significantly ameliorated in FM fed mice compared to db/db mice. Consistent with these results, the concentrations of serum total cholesterol, triglycerides, and LDL cholesterol were also significantly decreased in FM fed mice compared to db/db mice. However, the concentration of HDL cholesterol was significantly higher in FM fed mice compared to db/db mice. These results were similar to those of GLM, a commercial anti-diabetic drug. Therefore, our results suggest that FM has anti-diabetic effect as a functional food to treat type II diabetes mellitus.