• Korean Circulation Journal
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• v.53 no.1
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• pp.34-46
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• 2023

Background and Objectives: Diabetes mellitus (DM)-associated heart failure (HF) causes high morbidity and mortality. In this study, we established a zebrafish larvae model for in vivo research on diabetic HF. Methods: DM-like phenotypes were induced by treating zebrafish larvae with a combination of D-glucose (GLU) and streptozotocin (STZ). HF was induced by treatment with terfenadine (TER), a potassium channel blocker. Additionally, myocardial contractility, motility, and viability were evaluated. Results: The zebrafish larvae treated with a combination of GLU and STZ showed significantly higher whole-body glucose concentrations, lower insulin levels, and higher phosphoenolpyruvate carboxykinase levels, which are markers of abnormal glucose homeostasis, than the group treated with only GLU, with no effect on viability. When treated with TER, DM zebrafish showed significantly less myocardial fractional shortening and more irregular contractions than the non-DM zebrafish. Furthermore, in DM-HF with reduced ejection fraction (rEF) zebrafish, a significant increase in the levels of natriuretic peptide B, a HF biomarker, markedly reduced motility, and reduced survival rates were observed. Conclusions: We established a DM-HFrEF zebrafish model by sequentially treating zebrafish larvae with GLU, STZ, and TER. Our findings indicate the potential utility of the developed zebrafish larvae model not only in screening studies of new drug candidates for DM-HFrEF but also in mechanistic studies to understand the pathophysiology of DM-HFrEF.

• International Journal of Oral Biology
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• v.42 no.3
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• pp.137-142
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• 2017

To determine the effect of the tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) in odontoclast formation, we administrated a $TNF-{\alpha}$ inhibitor in rats with diabetes rats with periodontitis. The rats included in the study were divided into three groups: control rats without diabetes or periodontitis (the C group), rats with periodontitis and diabetes (the PD group), and rats with periodontitis and diabetes treated by infliximab, the TNF inhibitor (the PD+infliximab group). The PD and PD+infliximab groups received intravenous administrations of streptozotocin (STZ, 50 mg/kg) to induce diabetes. After 7 days of STZ injections, the mandibular first molars were ligatured to induce periodontitis. The PD+infliximab group was intrapenitoneally administrated by infliximab (5 mg/kg). On days 3 and 20 after the ligature administration, odontoclast formation along root surfaces was evaluated by tartrate resistant acid phosphatase (TRAP) staining and cathepsin K immunohistochemistry. On day 3, the number of TRAP- and cathepsin K-positive cells increased more so in the PD group than in the C group. The PD+infliximab group showed a lower number of positive cells than the PD group. There was no difference in all the groups on day 20. On day 3, the cathepsin-K positive multinucleated and mononucleated cells were higher in the PD group than in the C group. The number of cathepsin-K positive multinucleated cells was lower in the PD+infliximab group than in the PD group. The PD group showed more cathepsin K-positive cells in the furcation and distal surfaces than the c group. The Cathepsin K-positive cells of the PD+infliximab group were lower than that of the PD group in furcation. These results suggest that $TNF-{\alpha}$ stimulates odontoclast formation in diabetes with periodontitis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.2
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• pp.321-326
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• 2011

The aim of the present study was to investigate antihyperglycemic effect of Gleditschiae Spina (GS) in streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic rats. The rats were divided into four groups: normal control (NC), diabetic control (DC), diabetic rats supplemented with acarbose (AC, 4 mg/kg), and with GS ethanol extracts (GSE, 50 mg/kg). Weekly fasting blood glucose (FBG) for 10 weeks and oral glucose tolerance test (OGTT) at 10th week were monitored using glucose oxidase-peroxidase reactive strips. The FBG level was significantly reduced in AC group after 8 weeks and in GSE group at the end of period. The AUCs for the glucose response from OGTT and blood glucose level after sacrifice were significantly lower in the AC and GSE groups than the DC group. GSE supplementation significantly increased plasma total radical-trapping antioxidant potential (TRAP) in STZ-NA-induced diabetic rats, compared with DC group. The present study indicates that GSE could ameliorate type 2 diabetes and be comparable to acarbose, a standard hypoglycemic drug. Also, we suggest that GSE may possess antioxidant activity against the STZ-NA-induced oxidative stress.

• Journal of Nutrition and Health
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• v.42 no.1
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• pp.5-13
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• 2009

Mushrooms have become a largely untapped source of powerful new pharmaceutical products that poses anti-inflammatory, and antimutagenic, and antioxidant activities. The antioxidant effects of the mushroom may be partly explained by protecting cellular components against free radical. The aim of this study was to investigate the protective effect of chaga mushroom against diabetes, via the mitigation of oxidative stress and reduction of blood glucose, in streptozotocin-induced diabetic rats. Rats were rendered diabetic by intravenous administration of STZ through tail at a dose of 50 mg/kg. Animals were allocated into four groups with 8 rats each. The control and diabetic control group were fed with standard rat feed. The other diabeic groups, the low chaga extract group and the high chaga extract group were fed ad libitum using 0.5 g/kg and 5 g/kg of chaga mushroom extract, respectively, for 4 weeks. The blood glucose levels in the two chaga extract groups showed a tendency to decrease but did not reach statistical significance after the supplementation. Leukocyte DNA damage, expressed as tail length, was found to be significantly lower in the high chaga extract group than in the diabetic control group (p > 0.05). Plasma level of total radical-trapping antioxidant potential (TRAP) was tend to be higher in the high chaga extract group compared with the diabetic control group. Erythrocyte antioxidant enzyme activities of two groups did not differ. Although we did not obtain beneficial effect on lowering blood glucose levels in the STZ-induced diabetic rats, this results suggest that the chaga mushroom extracts may initially act on protecting endogenous DNA damage in the short-term experiment.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.2
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• pp.167-173
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• 2016

This study investigated the effects of green tea polyphenol and vitamin C on type 2 diabetes mellitus by administering polyphenon 60 (P60) and sodium ascorbate (SA) to diabetic rats induced by high fat diet/low-dose streptozotocin. The experimental group was divided into five different groups: non-diabetic control group (NC), diabetes control group (DC), diabetes+P60 group (DM+P60), diabetes+SA group (DM+SA), and diabetes+P60+SA group (DM+P60+SA). P60 and SA were dissolved in 0.1% drinking water. After P60 and SA were administered for 16 weeks, fasting blood glucose, plasma insulin, serum triglyceride, blood urea nitrogen (BUN), and creatinine levels as well as kidney alkaline phosphatase (AP) and ${\gamma}$-glutamyltranspeptidase (GGT) activities were measured. Fasting blood glucose level increased 5-fold in the DC group compared to the NC group. In the DM+P60 group, fasting blood glucose level decreased by 14%. In the DM+P60+SA group, fasting blood glucose level decreased by 28% compared to the DC group, whereas the DM+SA group did not show any significant difference. The homeostasis model assessment for insulin resistance index increased in the DC group and decreased in the DM+P60+SA group compared to the DC group. Serum creatinine level increased in the DC group, but decreased by 17% in the DM+P60 group and by 43% in the DM+P60+SA group compared to the DC group. The serum BUN level increased in the DC group, but decreased by 41% in the DM+P60+SA group compared to the DC group. Kidney GGT and AP activities decreased in the DC group compared to the NC group; however, they were reversed by DM+P60+SA group. These results show that combined administration of both green tea polyphenol and vitamin C had better effects on improving blood glucose level, insulin resistance, serum triglyceride level, and protecting kidneys than administration of either green tea polyphenol or vitamin C alone in the context of type 2 diabetes.

• Journal of Nutrition and Health
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• v.47 no.6
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• pp.394-402
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• 2014

Purpose: Dendropanax morifera Leveille (DML) exhibits diverse biological and pharmacological activities, including anti-oxidative effect, anti-cancer activity, hepatoprotection, immunological stimulation, and bone regeneration. As part of the identification for novel functions of DML, we investigated the therapeutic effects of DML on diabetes induced by streptozotocine (STZ) treatment. Methods: First, the four extracts including the water extract of leaf (DLW), the ethanol extract of leaf (DLE), the water extract of stem (DSW), and the ethanol extract of stem (DSE) were collected from the leaf and stem of DML using a hot water and ethanol solvent. Alterations in body weight, glucose concentration, insulin level, and pancreatic islet structure were investigated in diabetic mice after treatment with extracts of DML for 2 weeks. Results: Among four extracts, the highest level of total polyphenols and total flavonoids was detected in DLW, while the lowest level of these was measured in DSE. The radical scavenging activity was also higher in DLW than in the other three extracts at the concentration of $25-100{\mu}g/mL$, although this activity was maintained at a constant level in all groups at the concentration of $500{\mu}g/mL$. Based on the results of anti-oxidant activity, DLW and DLE were selected for examination of anti-diabetic effects in a diabetes model. Body weight was gradually decreased in all STZ treated groups compared with the No treated group. However, four STZ/DML treated groups maintained a high level of body weight during 7-14 days, while the STZ/vehicle treated group showed a gradual decrease of body weight during the same period. Also, a significant decrease or increase in the concentration of glucose and insulin in the blood of the diabetes model was detected in a subset of groups, although the highest increase was detected in the STZ/DLE-200 treated group. In addition, the histological structure of pancreatic islet was significantly recovered after treatment with DLW and DLE. Conclusion: These results suggest that DLW and DLE may contribute to attenuation of clinical symptoms of diabetes as well as prevent the destruction of pancreatic ${\beta}$-cells in STZ-induced diabetes mice.

• Korean Journal of Food Science and Technology
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• v.36 no.3
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• pp.465-471
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• 2004

This study was designed to investigate the effect of a butanol (BuOH) fraction of Alisma canaliculatum (Ac) with/without vitamin E (VE) on glycogen, lipid levels and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were divided into 5 groups: normal, STZ-control, and 3 diabetic experimental groups. Diabetes was induced by injection of STZ (45 mg) into the tail vein. The BuOH fraction of Ac and VE were administrated orally in rats for 21 days: Ac group (400 mg), Ac-VE group (Ac 400 mg & vitamin E 10 mg) and VE group (10 mg). Liver and muscle glycogen levels decrease in STZ-control group versus normal group and these alteration in glycogen levels were prevented Ac-VE group and VE group. Oral administration of Ac or VE resulted in reduction in liver cholesterol. Liver triglycerides were significantly higher in the VE group than in STZ-control group. Liver malondialdehyde (MDA) was increase in STZ-control group compared to normal group, but that of Ac group and Ac-VE group were similar to normal group. Meanwhile MDA in kidney, lung and pancreas were not significantly different among five groups. Ac-VE group increase lung protein that were significantly higher than diabetic control rats. These results suggest that the VE could increase glycogen and triglyceride levels and BuOH fraction of Ac decrease MDA of liver in the diabetic rats. The use of Ac together with VE did not show better control hyperglycemia-induced oxidative stress.

• Journal of Yeungnam Medical Science
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• v.9 no.1
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• pp.121-129
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• 1992

The effect of exercise on plasma insulin, free fatty acid, and glucose uptake and glycogen concentration in soleus, and intravenous glucose tolerance of streptozotocin treated, diabetic Sprague-Dawley rats were studied. Diabetic-trained animals were Subjected to a regular program of treadmill running for 4 weeks. Seventy-two hours after the last training session, basal and insulin-stimulated glucose uptake was studied in incubated strips(about 20mg) of soleus muscle in vitro. Glucose tolerance was measured with intravenous infusion of 0.5g glucose/kg body weight. In diabetic rats, training was associated with increased glucose uptake in basal and maximal insulin concentrations, decreased fasting glucose concentrations, and increased muscle glycogen levels, but there were no changes in glucose tolerance curve and plasma insulin concentrations. These results suggest that regular running program for 4 weeks improve responsiveness of insulin on soleus muscle, but fails to cause improvement of impaired intravenous glucose tolerance in mild degree streptozotocin induced diabetic rats.

• The Korean Journal of Food And Nutrition
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• v.17 no.3
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• pp.337-345
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• 2004

The purpose of this study was designed to observe the effects of the feeding Prunus persica Batsch var. davidiana Max. extract on the improvement of the blood glucose, lipid compositions in the serum of streptozotocin(STZ)-induced diabetic rats fed the experimental diets for 5 weeks. Concentrations of blood glucose, total cholesterol, atherosclerotic index, LDL, LDL-cholesterol, free-cholesterol, cholesteryl ester, triglyceride(TG) and phospholipid (PL) in serum were significantly higher in the STZ (55 mg/kg B.W.)-induced diabetic group (group 2) and STZ(I.P.)+Prunus persica 5.0 g% extract group(group 3) than those in the control group (group 1, basal diet + water). But the concentrations of blood glucose, total cholesterol, atherosclerotic index, LDL, LDL-cholesterol, free-cholesterol, cholesteryl ester, TG and PL in serum were remakably lower in the group 3 than those in the group 2. In the ratio of HDL-cholesterol concentration to total cholesterol and HDL-cholesterol concentration, Prunus persica 5.0 g% extract administration group(group 3) were higher percentage than in the group 2. The activities of aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase (LDH) and alkaline phosphatase(ALP) in serum were rather lower in the Prunus persica 5.0 g% extract administration group(group 3) than in the STZ- induced diabetic group (group 2). From the above results, it was suggested that the Prunus persica Batsch var. davidiana Max. were effective on the improvement of the blood glucose, lipid compositions in serum of STZ-induced diabetic rats. Moreover, in Prunus persica Batsch var. davidiana Max. was effective therapeutic regimen for the control of metabolic derangements in adult disease.

• Journal of Nutrition and Health
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• v.40 no.3
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• pp.199-210
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• 2007

The aim of this study was to investigate the effects of mulberry juice and cake powder on blood glucose and lipid status along with intestinal disaccharidase and erythrocyte antioxidative enzyme system in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats weighing $100{\pm}10g$ were randomly assigned to one normal group, and eight STZ-induced diabetic groups: control diet group without mulberry juice and cake powders (DM-C), three mulberry juice powder groups (0.5%: DM-0.5J, 1%: DM-1J, 2%: DM-2J) and low mulberry cake powder groups (0.25%: DM-0.25C, 0.5%: DM-0.5C, 1%: DM-1 C, 2%: DM-2C). After three-week feeding of each experimental diet, diabetes was induced by intravenous injection of 50 mg/kg body weight of STZ in sodium citrate buffer (pH 4.3) via tail vein of eight DM groups. Rats were sacrificed at the 9th day of diabetic states. Level of blood glucose was 505 mg/dl in DM-C group but it was 28% and 39% lower in mulberry juice and cake powder fed groups, respectively, than the DM-C group. Activities of maltase, sucrase and lactase in proximal part of small intestine were significantly lower in the mulberry juice and cake powder groups by $42{\sim}47%$ than those of DM-C group. Erythrocytic superoxide dismutase, glutathione peroxidase and catalase activities were significantly reduced by STZ but increased close to normal levels along with less accumulation of thiobarbituric acid reactive substances (TBARS). Serum levels of triglyceride and total cholesterol and HDL-cholesterol by STZ-DM were reduced and increased respectively, to the norma] levels by the mulberry juice and cake powder. Except the levels of TBARS, the effects on the other measurements by the various dietary levels of mulberry juice and cake powder were almost same and the effect of the cake powder was most significant at the lowest level. These results indicate that mulberry juice and cake powders have consityerable hypoglycemic effect and strengthening antioxidant defense systems at the low levels in diabetic state and may be able to reduce diabetic complications.