• International Journal of Oral Biology
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• 제37권3호
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• pp.85-90
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• 2012

Periodontal disease induces an increased incidence of tooth loss, particularly in cases with an associated loss of alveolar bone and periodontal ligaments. In this study, alveolar bone loss was detected by micro-computed tomography (CT) following exposure to E. coli lipopolysaccharide (LPS) in a streptozotocin (STZ)-induced diabetic mouse model. A 10 mg/ml dosage of E. coli LPS was applied between the first, second and third molars of the mice three times a week for 10 weeks. The loss of periodontal ligaments and alveolar processes was then evaluated by micro-CT using two and three dimensional microstructure morphometric parameters. In the diabetic mice, E. coli LPS induced the destruction of periodontal ligaments and loss of alveolar process spaces. The distances between periodontal ligaments were significantly widened in the STZ-LPS group compared with the untreated STZ group. The 10 mg/ml exposure to E. coli LPS in the STZ mice also resulted in a significant decrease in the alveolar bone volume fraction. The results of our study suggest that alveolar bone loss can be readily detected by volumetric micro-CT analysis as an increase in the distance between periodontal ligaments and in the alveolar process length.

• Molecules and Cells
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• 제40권7호
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• pp.457-465
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• 2017

Streptozotocin (STZ)-induced murine models of type 1 diabetes have been used to examine ER stress during pancreatic ${\beta}$-cell apoptosis, as this ER stress plays important roles in the pathogenesis and development of the disease. However, the mechanisms linking type 1 diabetes to the ER stress-modulating anti-diabetic signaling pathway remain to be addressed, though it was recently established that ERK5 (Extracellular-signal-regulated kinase 5) contributes to the pathogeneses of diabetic complications. This study was undertaken to explore the mechanism whereby ERK5 inhibition instigates pancreatic ${\beta}$-cell apoptosis via an ER stress-dependent signaling pathway. STZ-induced diabetic WT and CHOP deficient mice were i.p. injected every 2 days for 6 days under BIX02189 (a specific ERK5 inhibitor) treatment in order to evaluate the role of ERK5. Hyperglycemia was exacerbated by co-treating C57BL/6J mice with STZ and BIX02189 as compared with mice administered with STZ alone. In addition, immunoblotting data revealed that ERK5 inhibition activated the unfolded protein response pathway accompanying apoptotic events, such as, PARP-1 and caspase-3 cleavage. Interestingly, ERK5 inhibition-induced exacerbation of pancreatic ${\beta}$-cell apoptosis was inhibited in CHOP deficient mice. Moreover, transduction of adenovirus encoding an active mutant form of $MEK5{\alpha}$, an upstream kinase of ERK5, inhibited STZ-induced unfolded protein responses and ${\beta}$-cell apoptosis. These results suggest that ERK5 protects against STZ-induced pancreatic ${\beta}$-cell apoptosis and hyperglycemia by interrupting the ER stress-mediated apoptotic pathway.

• 한국식품영양학회지
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• 제28권2호
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• pp.171-177
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• 2015

본 동물실험은 STZ로 유도한 C57BL/6에게 5% sodium butyrate를 급여했을 때 항당뇨 및 항염증 효과를 연구하고자 하였다. 본 연구에서 STZ로 당뇨를 유발한 마우스에게 5% sodium butyrate를 급여했을 때 체중과 식이섭취량에서는 크게 유의적 차이가 없음을 확인하였다(p<0.05). STZ에 의한 당뇨 쥐는 인슐린의 분비가 감소되면서 당대사의 불균형을 초래하며 간 등이 비대해진다고 알려져 있으나, 본 연구에서는 간의 장기 무게에서는 크게 실험군 간에 유의적인 차이가 없었다(p<0.05). 또한 비장과 흉선의 무게는 0.5% sodium butyrate 첨가 식이군에서 유의적으로 낮아짐을 알 수 있었다(p<0.05). 당뇨병은 염증 상태로서 고혈당으로 인하여 monocyte에서는 여러 염증성 사이토카인이 분비가 활성화된다. TNF-${\alpha}$, IL-6 등은 염증성 사이토카인으로서 혈관염증의 중요한 마커로 인식되고 있고, 당뇨병 환자들은 이러한 염증성 사이토카인이 높은 수준으로 활성화 된다. STZ 처리 시 마우스 혈청에서의 염증성 사이토카인의 분비 및 발현이 증가되었으나, 5% sodium butyrate를 급여했을 때 염증성 사이토카인의 분비 및 발현이 저해됨을 확인할 수 있었다. 본 연구는 sodium butyrate 보충은 당뇨병이 유발된 동물모델에서 혈청지질 농도 및 혈당 조절, 염증 상태를 개선에 다소간의 효과가 있는 것으로 나타났다. 이에 따라 당뇨병과 같은 만성적인 대사질환 개선에 sodium butyrate가 효과적인 식이인자가 될 것으로 생각된다. 그러나 앞으로 더 명확한 효능을 탐색하기 위해서 시료 첨가수준의 다각화 및 여러 가지 보완연구가 필요할 것으로 생각 된다.

• 한국식품영양학회지
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• 제26권2호
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• pp.310-317
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• 2013

To investigate the effects of coated liposome from Discorea rhizoma extract (DRE) in streptozotocin (STZ)-induced, we evaluated changes in body weight, fasting blood glucose, blood insulin and blood lipid concentrations in mice. Mice were divided into four groups: (DC), diabetic DRE at 10 mg/kg (DRE-1), diabetic DRE at 50 mg/kg (DRE-2), and diabetic DRE at 250 mg/kg (DRE-3). Mice had free access to water and diet (10 weeks). The DC group showed higher blood cholesterol than the DRE-1, DRE-2, DRE-3 groups. In glucose tolerance test, the DRE-1, DRE-2, and DRE-3 groups increased after 30 minutes in decremental glycemic response area under the curve. Fasting blood glucose levels in the DRE groups significantly decreased through 4 weeks. Plasma total cholesterol, triglyceride and LDL-cholesterol concentrations were also lower in the DRE groups. On the other hand, the DRE-1, DRE-2 and DRE-3 groups showed higher HDL-cholesterol and insulin levels than the DC group. Moreover, blood glucose and lipid levels significantly decreased in streptozotocin (STZ)-induced diabetic mice treated with DRE. These results indicate that DRE may reduce elevated blood glucose levels and serum lipid concentrations in hypoglycemic and diabetic mice, suggesting its usefulness as a functional food.

• Preventive Nutrition and Food Science
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• 제21권3호
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• pp.181-186
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• 2016

This study was designed to investigate the inhibitory effect of Gynura procumbens extract against carbohydrate digesting enzymes and its ability to ameliorate postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. G. procumbens extract showed prominent ${\alpha}$-glucosidase and ${\alpha}$-amylase inhibitory effects. The half-maximal inhibitory concentration ($IC_{50}$) of G. procumbens extract against ${\alpha}$-glucosidase and ${\alpha}$-amylase was $0.092{\pm}0.018$ and $0.084{\pm}0.027mg/mL$, respectively, suggesting that the ${\alpha}$-amylase inhibition activity of the G. procumbens extract was more effective than that of the positive control, acarbose ($IC_{50}=0.164mg/mL$). The increase in postprandial blood glucose levels was more significantly alleviated in the G. procumbens extract group than in the control group of STZ-induced diabetic mice. Moreover, the area under the curve significantly decreased with G. procumbens extract administration in STZ-induced diabetic mice. These results suggest that G. procumbens extract may help alleviate postprandial hyperglycemia by inhibiting carbohydrate digesting enzymes.

• Preventive Nutrition and Food Science
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• 제14권1호
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• pp.8-13
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• 2009

This study investigated the hypoglycemic effect of fermented soymilk extract (FSE) in STZ-induced diabetic mice. FSE was prepared via fermentation of soymilk with Bacillus subtilis followed by methanol extraction. The hypoglycemic effect was determined by inhibitory activities against ${\alpha}$-glucosidase and ${\alpha}$-amylase as well as the alleviation of postprandial glucose level. The non-fermented soymilk extract (SE) was used as control in this experiment. FSE showed higher (p<0.05) inhibitory activities than SE against ${\alpha}$-glucosidase and ${\alpha}$-amylase. The $IC_{50}$ values of FSE for ${\alpha}$-glucosidase and ${\alpha}$-amylase were 0.77 ancd 0.94 mg/mL, respectively, which were comparable or even superior to those of acarbose (0.79 and 0.68 mg/mL, respectively). In addition, a further suppression on the postprandial blood glucose levels were observed in the FSE than SE group for both STZ-induced diabetic mice and normal mice. Furthermore, FSE significantly lowered the incremental area under the curve (AUC) in the diabetic mice and the AUC in normal mice corroborated the hypoglycemic effect of FSE (p<0.05). Results from this study suggest that FSE may help decrease the postprandial blood glucose level via inhibiting ${\alpha}$-glucosidase and ${\alpha}$-amylase and the usefulness of FSE was proven to be better than SE.

• Advances in Traditional Medicine
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• 제9권1호
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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.

• 대한본초학회지
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• 제30권1호
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• pp.1-9
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• 2015

Objectives : The present study was designed to investigate the anti-diabetic effects of Mori Folium (Morus alba L. of Moraceae) extract (MFE) on high fat diet (HFD) and streptozotocin (STZ)-induced type II diabetes mellitus in mice. Methods : The mice (C57BL/6J) were fed HFD for 8 weeks and then was induced with a single injection of STZ (75 mg/kg). The diabetic mice were divided into four groups [(STD, HFD, HFD + MFE and HFD + quercetin (QUR)] and administered with MFE or OUR for 4 weeks. Fasting blood glucose, lipid profile (triglycerides and cholesterol etc.), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), insulin and leptin were measured every 2 weeks. Results : Body weight gain was lower in the MFE and QUR groups than HFD group. The fasting blood glucose was lower in the MFE and QUR groups. Oral glucose and insulin tolerance were decreased in the MFE and QUR groups. The levels of serum total cholesterol, triglycerides, and LDL cholesterol were reduced in the MFE and QUR groups. The HDL cholesterol was much higher in the MFE and QUR groups than HFD group. The levels of GOT, GPT and atherogenic index were decreased in the MFE and QUR groups. The serum insulin and leptin concentrations were reduced in the MFE and QUR groups. Conclusions : These results showed that MFE could decrease blood glucose level and lead to an amelioration in dyslipidemia states on HFD/STZ-induced type II diabetes mellitus in mice.

• 한국식품영양과학회지
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• 제41권6호
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• pp.774-781
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• 2012

본 연구는 고지방식이와 STZ으로 유도한 제2형 당뇨마우스에게 CA를 급여하였을 때 체내 당대사와 항산화방어계에 미치는 영향을 규명하고자 하였다. 4주령 ICR 마우스를 고지방식이(전체 열량의 37% 지방)를 4주간 급여하여 인슐린저항성을 유발한 후 STZ(100 mg/kg body weight)을 일회복강주사 하였다. 7일 후 공복 시 혈당이 14 mmol/L(250 mg/dL)인 마우스만을 사용하여 난괴법으로 당뇨대조군, 0.02% CA군, 0.05% CA군으로 나누어 6주간 사육하였다. 실험 6주 동안 당뇨대조군에 비하여 두 CA 급여 수준은 혈당을 효과적으로 낮추었으며 내당능과 인슐린내성을 개선하였다. 또한 혈장 중의 렙틴 함량은 CA 급여 시 당뇨대조군에 비하여 높았으나 인슐린과 C-peptide 함량 및 체중에는 영향을 미치지 않았다. CA 급여는 당뇨대조군에 비하여 간조직의 GK활성을 높였고 G6Pase 활성은 낮춘 반면, PEPCK 활성에는 영향을 미치지 않았다. 간조직 중의 SOD와 CAT 활성은 CA급여군에서 당뇨대조군에 비하여 유의적으로 높았으나, GSH-Px 활성과 적혈구의 항산화 효소 활성은 실험군간 유의적인 변화가 없었다. 두 수준의 CA 급여는 간조직과 적혈구 중의 지질과산화물 함량을 당뇨대조군에 비하여 유의적으로 낮추었다. 이와 같이 CA는 간조직에서 당 이용을 높이는 반면, 당 신생을 억제함으로써 혈당저하에 효과적이었으며 항산화방어계를 활성화하여 지질과산화물 생성을 개선하는데 효과적인 것으로 나타났다.

• 생명과학회지
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• 제27권9호
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• pp.1052-1058
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• 2017

우뭇가사리(Gelidium amansi)는 홍조류로서 우뭇가사리과(Gelidiaceae)에 속한다. 현재까지 우뭇가사리의 항산화 및 항비만 효과 등의 기능들이 연구되었으나 식후 혈당 수치에 미치는 영향에 관한 연구는 부족한 실정이다. 이에 본 연구에서는 Gelidium amansii extract (GAE)가 탄수화물 가수분해 효소(${\alpha}-glucosidase$, ${\alpha}-amylase$)에 미치는 억제 효과 및 streptozotocin (STZ)으로 유도된 당뇨병 마우스의 식후고혈당에 미치는 완화효과를 조사하였다. 정상군과 STZ으로 유도된 당뇨병 마우스에 수용성 전분(2 g/kg body weight)을 경구투여한 후 GAE (300 mg/kg body weight) 또는 acarbose (100 mg/kg body weight)를 단독 또는 함께 투여하였다. 혈당은 꼬리채혈을 통해 0, 30, 60, 120분 간격으로 측정하였다. ${\alpha}-glucosidase$와 ${\alpha}-amylase$에 대한 GAE의 $IC_{50}$ 값은 각각 $0.099{\pm}0.009mg/ml$와 $0.178{\pm}0.038mg/ml$의 결과값을 나타내어, 양성대조군인 acarbose보다 더 효과적이었다. STZ으로 유발된 당뇨병 마우스의 식후 혈당 수치는 대조군에 비해 GAE 투여 시 유의적으로 더 낮았다(p<0.05). 또한 GAE 투여는 당뇨병 마우스에서 포도당 반응에 대한 곡선하면적 감소와 관련이 있었다(p<0.05). 이러한 결과는 GAE가 ${\alpha}-glucosidase$, ${\alpha}-amylas$와 같은 탄수화물 가수분해 효소를 억제함으로써 식후 고혈당을 완화시키는 유용한 천연기능성 식품이 될 것으로 사료된다.