• IMMUNE NETWORK
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• 제4권1호
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• pp.53-59
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• 2004

Background: Minor histocompatibility HY antigen, as a transplantation antigen, has been known to cause graft rejection in MHC (major histocompatibility complex) matched donor-recipient. The aim of our study is to investigate the role of male antigen (HY) disparity on MHC matched pancreatic islet transplantation and to examine the mechanism of the immune reaction. Methods: Pancreatic islets were isolated and purified by collagen digestion followed by Ficoll gradient. The isolated islets of male C57BL6/J were transplanted underneath the kidney capsule of syngeneic female mice rendered diabetic with streptozotocine. Blood glucose was monitored for the rejection of engrafted islets. After certain period of time, tail to flank skin transplantation was performed either on mouse transplanted with HY mismatched islets or on sham treated mouse. The rejection was monitored by scoring gross pathology of the engrafted skin. Results: HY mismatched islets survived more than 300 days in 14 out of 15 mice. The acceptance of second party graft (male B6 islets) and the rejection of third party graft (male BALB/c islets) in these mice suggested the tolerance to islets with HY disparity. B6 Skin with HY disparity was rejected on day $25{\pm}7$. However, HY mismatched skin transplanted on the mice tolerated to HY mismatched islets survived more than 240 days. Tetramer staining in these mice indicated the CTL recognizing MHC Db/Uty was not deleted or anergized. Conclusion: The islet transplantation across HY disparity induced tolerance to HY antigen in C57BL6 mouse, which in turn induced tolerance to HY mismatched skin, which otherwise would be rejected within 25 days. The MHC tetramer staining suggested the underlying mechanisms would not be clonal deletion or anergy.

• 한국식품영양학회지
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• 제35권6호
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• pp.513-520
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• 2022

The purpose of this study was to investigate the effect of Cheonggukjang pills with aronia and blueberries on dextran sulfate sodium (DSS)-induced colitis in mice. There have been several reports that Cheonggukjang is effective for intestinal health, but the efficacy of Cheonggukjang containing fruits has not yet been reported. In this study, we showed the effect of cheonggukjang pills with blueberries and aronia (CPBA) on DSS-induced colitis in BALB/c mice. CPBA was obtained from Soonchang Moonokae foods and orally administered once a day for 2 weeks before DSS treatment. Colitis was induced in mice by feeding 5% (w/v) DSS drinking water for 7 days. The results showed that CPBA treatment significantly alleviated DSS-induced disease activity index associated with a decrease in colon length. CPBA improved DSS-induced histological changes and intestinal epithelial barrier integrity in mice colon. In addition, CPBA administration significantly reduced the levels of DSS-mediated interferon-γ and interleukin-6 in serum and tumor necrosis factor-α in colon tissue. Moreover, the gene expression of COX-2 and iNOS, which are factors involved in inflammatory signaling, was significantly reduced by CPBA treatment. These results suggest that CPBA have a protective effect against DSS-induced mice colitis and may be a candidate for colitis treatment.

• 한국식품영양과학회지
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• 제42권6호
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• pp.885-891
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• 2013

유색보리와 귀리를 이용한 당뇨환자용 즉석죽의 당뇨 개선 효과를 in vivo를 통하여 확인하고 다음과 같은 결과를 얻었다. Type II 당뇨병 모델 생쥐(C57BLKS/J lar-$+Lepr^{db}/+Lepr^{db}$)의 실험종료 후 혈당의 농도는 대조군에서는 $426.0{\pm}15.4$ mg/dL이었으나, 실험군에서는 $352{\pm}12.2$ mg/dL로 약 17.4% 감소하였다. Streptozotocin으로 유발시킨 당뇨병 모델 SD계 rat의 실험종료 후 혈당의 농도는 대조군에서 $514.0{\pm}17.6$ mg/dL이었으나, 실험군에서는 $296.4{\pm}13.2$ mg/dL로 42.3% 감소하였다. Type II 당뇨병 모델 생쥐의 혈중내 인슐린 농도는 대조군에서 $7.9{\pm}0.5$ ng/mL이었으나, 실험군에서는 $12.8{\pm}1.1$ ng/mL로 약 38.3% 증가하였다. Type II 당뇨병 모델 생쥐의 췌도 내 인슐린 분비세포와 glucagon like peptide-1 분비세포에 대한 면역염색 반응은 실험군에서 대조군에 비해 췌도 내 인슐린 분비세포에 대한 면역염색 반응이 강하게 관찰되었고, streptozotocin으로 유발시킨 당뇨병 모델 SD계 rat의 췌도 내 인슐린 분비세포 및 glucagon like peptide-1 분비세포에 대한 면역염색 반응 또한 실험군에서 대조군에 비하여 인슐린 분비세포에 대한 면역염색 반응이 강하게 관찰되었다. 이상의 실험결과로 당뇨환자용 즉석죽은 당뇨병 유발 쥐들에서 췌도 내 인슐린 분비세포 기능의 활성화를 통한 인슐린의 분비를 촉진시키고, 혈당을 저하시킴을 알 수 있었다.

• 한국발생생물학회지:발생과생식
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• 제23권3호
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• pp.223-229
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• 2019

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR). T2DM is correlated with obesity and most T2DM medications have been developed for enhancing insulin sensitivity. Silk protein fibroin (SPF) from spiders has been suggested as an attractive biomaterial for medical purposes. We generated transgenic rice (TR) expressing SPF and fed it to diabetic $BKS.Cg-m+/+Lepr^{db}$ mice to monitor the changes in blood glucose levels and adipose tissue proteins associated with energy metabolism and insulin signaling. In the present study, the adipocyte size in abdominal fat in TR-SPF-fed mice was remarkably smaller than that of the control. Whereas the adenosine monophosphate-activated protein kinase (AMPK)-activated protein kinase and insulin receptor substrate 1 (IRS1) protein levels were increased in abdominal adipose tissues after TR-SPF feeding, levels of six-transmembrane protein of prostate 2 (STAMP2) proteins decreased. Phosphorylation of AMPK at threonine 172 and IRS1 at serine 307 and tyrosine 632 were both increased in adipose tissues from TR-SPF-fed mice. Increased expression and phosphorylation of IRS1 at both serine 307 and tyrosine 632 in adipose tissues indicated that adipocytes obtained from abdominal fat in TR-SPF-fed mice were more susceptible to insulin signaling than that of the control. STAMP2 protein levels decreased in adipose tissues from TR-SPF-fed mice, indicating that STAMP2 proteins were reducing adipocytes that were undergoing lipolysis. Taken together, this study showed that TR-SPF was effective in reducing blood glucose levels in diabetic mice and that concurrent lipolysis in abdominal adipocytes was associated with alterations of AMPK, IRS1, and STAMP2. Increased IRS1 expression and its phosphorylation by TR-SFP were considered to be particularly important in the induction of lipolysis in adipocytes, as well as in reducing blood glucose levels in this animal model.

• 한국발생생물학회지:발생과생식
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• 제24권3호
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• pp.231-239
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• 2020

Many benefits of silk protein fibroin (SPF) have been suggested in biomedical applications; and notably, significant SPF effects have been observed for metabolic syndromes that are directly linked to insulin resistance, such as type 2 diabetes mellitus (T2DM). Based on our previous findings, we believe that SPF from spiders exhibits outstanding glucose-lowering effects in diabetic BKS.Cg-m+/+Lepr^db mice. In order to evaluate the dietary effects of SPF in diabetic animals, we generated several lines of transgenic rice (TR) that expresses SPF, and the feeding of TR-SPF to diabetic animals decreased blood glucose levels, but did not change insulin levels. Western blot analyses of hepatic proteins showed that AMP-activated protein kinase (AMPK) expression and phosphorylation both decreased in TR-SPF-fed groups, compared with controls. This finding suggests that the glucose-lowering effects in this diabetic animal model might be AMPK-independent. In contrast, six-transmembrane protein of prostate 2 (STAMP2) was upregulated after TR-SPF exposure. Together with STAMP2, the Akt protein phosphorylation increased after TR-SPF exposure, which indicates that STAMP2 leads to Akt phosphorylation and thus increases insulin sensitivity in hepatocytes. Importantly, the hepatic steatosis that was seen in the liver of diabetic mice was remarkably alleviated in TR-SPF-fed mice. Hepatocytes that were immunopositive for STAMP2 were overwhelmingly observed in hepatic tissues from TR-SPF-fed mice compared to the control. Taken together, these results suggest that feeding diabetic mice with TR-SPF upregulates STAMP2 expression and increases Akt phosphorylation in hepatic tissues and thus potentially alleviates insulin resistance and hepatic steatosis.

• Nutrition Research and Practice
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• 제4권6호
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• pp.486-491
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• 2010

Tight control of blood glucose is the most important strategy for the treatment of diabetes mellitus. Here, we investigated the beneficial effects of Welsh onion on fasting and postprandial hyperglycemia. Inhibitory activities of hot water extracts from the green stalk and white bulb, which are the edible portions of the Welsh onion, and the fibrous root extract against yeast ${\alpha}$-glucosidase were measured in vitro. To study the effects of Welsh onion on postprandial hyperglycemia, a starch solution (1 g/kg) with and without Welsh onion fibrous root extract (500 mg/kg) or acarbose (50 mg/kg) was administered to streptozotocin-induced diabetic rats after an overnight fast. Postprandial plasma glucose levels were measured and incremental areas under the response curve were calculated. To study the hypoglycemic effects of chronic feeding of Welsh onion, five-week-old db/db mice were fed an AIN-93G diet or a diet containing either Welsh onion fibrous root extract at 0.5% or acarbose at 0.05% for 7 weeks after 1 week of adaptation. Fasting plasma glucose and blood glycated hemoglobin were measured. Compared to the extract from the edible portions of Welsh onion, the fibrous root extract showed stronger inhibition against yeast ${\alpha}$-glucosidase, with an $IC_{50}$ of 239 ${\mu}g/mL$. Oral administration of Welsh onion fibrous root extract (500 mg/kg) and acarbose (50 mg/kg) significantly decreased incremental plasma glucose levels 30-120 min after oral ingestion of starch as well as the area under the postprandial glucose response curve, compared to the control group (P < 0.01). The plasma glucose and blood glycated hemoglobin levels of the Welsh onion group were significantly lower than those of the control group (P < 0.01), and were not significantly different from those fed acarbose. Thus, we conclude that the fibrous root of Welsh onion is effective in controlling hyperglycemia in animal models of diabetes mellitus.