• 대한수의학회지
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• 제44권4호
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• pp.497-505
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• 2004

The proliferation of mesangial cells has been associated with the development of diabetic nephropathy. The cell proliferation has been regulated by diverse growth factors. Among them, insulin like growth factors(IGFs) are also involved in the pathogenesis of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I and IGF-II secretion and the relationship between high glucose-induced secretion of IGFs and PKC or oxidative stress in the mesangial cells. Thus, we examined the mechanisms by which high glucose regulates secretion of IGFs in mesangial cells. High glucose(25 mM) increased IGF-I and IGF-II secretion. High glucose-induced increase of IGF-I and IGF-II secretion were blocked by taurine($2{\times}10^{-3}$ M), N-acetyl cystein(NAC, $10^{-5}M$), or GSH($10^{-5}M$) (antioxidants), suggesting the role of oxidative stress. High glucose-induced secretion of IGF-I and IGF-II were blocked by H-7, staurosporine, and bisindolylmaleimide I(protein kinase C inhibitors). On the other hand, high glucose also increased lipid peroxide (LPO) formation in a dose dependent manner. In addition, high glucoseinduced stimulation of LPO formation was blocked by PKC inhibitors. These results suggest that PKC is responsible for the increase of oxidative stress in the action of high glucose-induced secretion of IGF-I and IGF-II in mesangial cells. In conclusion, high glucose stimulates IGF-I and IGF-II secretion via PKCoxidative stress signal pathways in mesangial cells.

• 생명과학회지
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• 제20권7호
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• pp.1027-1033
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• 2010

맥문동(Liriope platyphylla)은 한국과 중국에서 전통적으로 당뇨, 비만, 뇌신경질환, 천식 등의 치료를 위해 사용 해온 치료제이다. 최근에 이들 맥문동으로부터 새로운 치료제를 개발하려는 노력이 활발히 진행 중이지만 아직도 유력한 치료후보제는 확보되지 않았다. 따라서 본 연구에서는 맥문동의 새로운 추출물을 이용하여 당뇨치료 제로서의 가능성을 평가하기 위하여 새로운 방법으로 10가지 후보물질을 추출하고 이들의 독성과 효능을 평가하였다. 그 결과 10가지 추출물 중에서 LP9M80-H가 인슐린 분비를 가장 많이 촉진하였고 다음으로는 LP-H, LP-M, LP-E과 LP9M80-C 등의 순서로 촉진을 하였으나 나머지는 인슐린 분비를 촉지하지 못하였다. 그러나 이들 물질은 인슐린 분비를 촉진하는 농도에서 강한 세포 독성을 나타내었다. 따라서 이들 물질 중에서 가장 효능이 좋은 LP9M80-H의 치료용 최적농도를 설정하였으며, 대략 100-25 ug/ml가 최적농도로 결정되었다. 이러한 결과는 맥문동 추출물 중에서 LP9M80-H가 췌장 $\beta$-세포의 인슐린 분비능을 유도하는 새로운 당뇨치료 후보물질로서 향후에 사용될 가능성을 시사하고 있다.

• 대한간호학회지
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• 제27권3호
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• pp.694-704
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• 1997

This study was designed to assess the body fat distribution, and also to investigate the effects of body fat on glucose tolerance and on insulin secretion pattern by body mass index in offspring of parents with NIDDM. The subjects consisted of twenty parents with NIDDM who had been admitted to the Department of Internal Medicine or had been seen in the outpatient clinic at Kangnam St. Mary's Hospital, Catholic University between February to March, 1995. Twenty offspring were randomly selected from forty six offspring of twenty parents with NIDDM. As a control group, twenty healthy people without a family history of diabetes mellitus were matched by sex, age and body mass index(BMI). The results are as follows : 1. Mean fasting serum glucose and insulin levels and insulin / glucose ratio were significantly greater in offspring than in the control subjects with BMI 25kg /㎡ in the offspring and in the BMI<25kg /㎡ control subjects (P<0.05). 2. The total glucose area and insulin area were significantly greater in both the offsping and the control subjects with BMI≥25kg /㎡ than in both the offspring and the control subjects with BMI<25 kg /㎡(P<0.05). 3. Upper body skinfold thickness, Waist hip ratio(WHR), serum levels of total cholesterol and triglyceride(TG), total dietary calorie intake and protein intake in both the offspring and the control subjects with BMI≥25kg /㎡ were greater than those with BMI<25kg /㎡(P<0.05). On the other hand, HDL-cholesterol in both the offspring and the control subjects with BMI≥25kg /㎡ was lower than those with BMI< 25kg /㎡(P<0.05). 4. The major variables influencing the total glucose area were subscapular skinfold thickness and WHR and the major variables influencing the total insulin area were suprailiac skinfold thickness, WHR, TG and free fatty acid. In the light of the results, glucose intolerance and insulin resistance were affected by body mass index, Upper body fat, WHR and lipids(TG, Free fatty acid), it is implied that these are influencing factors on total glucose area and total insulin area. The identification of these factors might provide a useful tool to identify individuals at high risk of diabetes mellitus. Therefore, various nursing intervention programs to reduce obesity could be given to both the offspring of parents with NIDDM and to the obese healthy controls before diabetes mellitus develops.

• Asian-Australasian Journal of Animal Sciences
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• 제20권10호
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• pp.1575-1579
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• 2007

The glucose tolerance and pancreatic insulin secretion response to glucose in sheep fed on germinated sorghum grain were determined using an intravenous glucose load. Twelve male Thin Tail sheep (an Indonesian native sheep, 12 months old and 14.8 kg average body weight) were divided randomly into sorghum grain-based (S), germinated sorghum grain-based (G) and maize grain-based (C) diets. Sheep were maintained at the same daily intake levels of metabolizable energy and crude protein in the diets throughout the experimental period. After two months of the experimental conditions, each diet group was subjected to an intravenous glucose load experiment in which five doses of glucose (0, 10, 20, 40 and 80 mg/kg BW) were injected to estimate the rate of glucose removal from blood and the pancreatic insulin secretion response. For each sheep and each glucose load dose, the incremental blood serum glucose and insulin concentrations above pre-injection concentration were calculated as serum glucose and insulin response areas. At all glucose doses, sheep fed on S diet had a greater (p<0.05) glucose response area compared to those of sheep fed on G and C diets. Likewise at all glucose doses, the insulin response area was smaller (p<0.05) in sheep fed on S diet than in sheep fed on G and C diets. The glucose and insulin response areas in sheep fed on G and C diets differed slightly. It was concluded that the portion of maize grain in the ruminant ration could be substituted by germinated sorghum grain.

• Journal of Ginseng Research
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• 제31권2호
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• pp.79-85
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• 2007

진세노사이드의 인슐린 분비 활성을 비교해 본 결과 PPD 계열 진세노사이드가 인슐린의 분비를 촉진하는 경향을 보였으며, 그 중에서도 CK의 인슐린 분비 촉진 효과가 가장 뛰어났다. CK는 RIN-m5F cell line과 일차 배양한 췌장 소도 세포에서 용량 의존적으로 인슐린의 분비를 촉진하였고 이러한 CK의 인슐린 분비 촉진 기전은 ATP-sensitive $K^+$ 채널의 봉쇄에 의한 것임을 확인하였다. H4IIE cell line에서 간 세포내 당신생과 관련된 효소의 발현을 측정한 결과 CK는 dexamethasone/cAMP에 의한 PEPCK 와 G6Pase의 발현을 억제하였다. 이로 미루어 볼 때, CK는 간에서 당의 신생을 억제하여 공복 시 혈당을 감소시킬 수 있음을 시사하였다. 또한 3T3-L1 cell line에서 TG의 함량과 $PPAR-{\gamma}$ 유전자의 발현에 미치는 영향을 살펴본 결과 CK는 $PPAR-{\gamma}$의 발현을 억제하여 결과 지방세포의 분화를 억제하였다. 결론적으로 CK는 췌장에서 ATP-sensitive $K^+$ channel을 봉쇄함으로 인슐린 분비를 촉진시키고 또한 간세포에서 당 신생을 억제함으로 식후 및 공복 시 혈당을 감소시킬 것으로 기대된다.

• 한국수정란이식학회지
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• 제20권1호
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• pp.71-77
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• 2005

Relaxin과 insulin이 돼지 난포 과립막세포의 스테로이드 호르몬 분비에 미치는 영향을 연구하기위하여 체외에서 황체화된 과립막세포에서 prosesterone과 $17{\beta}-estradiol$의 생산을 조사하였다. 돼지난포 과립막세포를 혈청 존재하에 배양접시에 부착 후 48시간 동안 체외배양하고 무혈청 배지에서 24시간 배양하였다. Relaxin과 insulin의 용량의존성을 확인하기 위하여 다양한 농도 (10, 100, 1,000 ng/ml)를 각각 무혈청 배지에 첨가하였다. 병합 효과를 알아보기 위하여 100 ng/ml relaxin과 100 ng/ml insulin을 단독 혹은 병합하여 처리하였는데 황체호르몬 (100 ng/ml)을 처리한 경우와 처리하지 않은 경우 모두를 조사, 분석하였다. 최종 배양이 끝난 배양액을 수집하여 RIA법으로 proses-terone과 $17{\beta}-estradiol$의 농도를 조사하였다. Relaxin과 insulin은 용량이 증가될수록 progesterone의 생산을 증가시켰으나 $17{\beta}-estradiol$의 생산에는 아무런 영향이 없었다. 병합실험에서는 relaxin과 insulin 단독 또는 병합시 황체호르몬 존재 하에서 progesterone의 생산을 증가시켰으나 $17{\beta}-estradiol$의 생산에는 아무런 영향이 없었다. 결론적으로 relaxin과 insulin은 돼지 황체화 과립막세포의 progesterone 분비를 증가시키지만 $17{\beta}-estradiol$의 생산에는 효과가 없었으며 병합에 의한 상승효과는 없었다. Progesterone 생산에 미치는 relaxin과 insulin의 효과는 황체호르몬의 존재에 의해 증대되었다.

• Nutrition Research and Practice
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• 제10권1호
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• pp.11-18
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• 2016

BACKGROUND/OBJECTIVES: Type 2 diabetes (T2D) is more frequently diagnosed and is characterized by hyperglycemia and insulin resistance. $\small{D}$-xylose, a sucrase inhibitor, may be useful as a functional sugar complement to inhibit increases in blood glucose levels. The objective of this study was to investigate the anti-diabetic effects of $\small{D}$-xylose both in vitro and stretpozotocin (STZ)-nicotinamide (NA)-induced models in vivo. MATERIALS/METHODS: Wistar rats were divided into the following groups: (i) normal control; (ii) diabetic control; (iii) diabetic rats supplemented with a diet where 5% of the total sucrose content in the diet was replaced with $\small{D}$-xylose; and (iv) diabetic rats supplemented with a diet where 10% of the total sucrose content in the diet was replaced with $\small{D}$-xylose. These groups were maintained for two weeks. The effects of $\small{D}$-xylose on blood glucose levels were examined using oral glucose tolerance test, insulin secretion assays, histology of liver and pancreas tissues, and analysis of phosphoenolpyruvate carboxylase (PEPCK) expression in liver tissues of a STZ-NA-induced experimental rat model. Levels of glucose uptake and insulin secretion by differentiated C2C12 muscle cells and INS-1 pancreatic ${\beta}$-cells were analyzed. RESULTS: In vivo, $\small{D}$-xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reduced the area under the glucose curve, and increased insulin levels compared to the diabetic controls. $\small{D}$-xylose supplementation enhanced the regeneration of pancreas tissue and improved the arrangement of hepatocytes compared to the diabetic controls. Lower levels of PEPCK were detected in the liver tissues of $\small{D}$-xylose-supplemented rats (P < 0.05). In vitro, both 2-NBDG uptake by C2C12 cells and insulin secretion by INS-1 cells were increased with $\small{D}$-xylose supplementation in a dose-dependent manner compared to treatment with glucose alone. CONCLUSIONS: In this study, $\small{D}$-xylose exerted anti-diabetic effects in vivo by regulating blood glucose levels via regeneration of damaged pancreas and liver tissues and regulation of PEPCK, a key rate-limiting enzyme in the process of gluconeogenesis. In vitro, $\small{D}$-xylose induced the uptake of glucose by muscle cells and the secretion of insulin cells by ${\beta}$-cells. These mechanistic insights will facilitate the development of highly effective strategy for T2D.

• 대한의생명과학회지
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• 제6권4호
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• pp.229-235
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• 2000

췌장에서 분비하는 인슐린과 글루카곤의 자극-분비 coupling 과정은 주로 혈당 농도와 중추신경계에 의하여 조절되어진다. 본 연구는 두부에 포도당이 결핍되었을 때에 중추신경계가 췌장에서 인슐린과 글루카곤이 분비되는 패턴을 Sprague-Dawley 흰쥐를 대상으로 하여 살펴보았으며, 실험 방법은 in situ 뇌-췌장 관류법을 이용하였다. 관류액은 100 mg/dL glucose와 20 mM arginine를 포함한 Krebs-Ringer 완충액 (pH 7.4)으로 하였으며, 95% $O_2$-5% $CO_2$ 가스를 계속적으로 주입시키면서 5 ml/min의 속도로 30분간 정주하였다. 대조군은 cephalic glucopenia가 일어나지 않는 군으로 하였고, 실험군은 두 군으로 나누어서 GLP1군은 cephalic glucopenia가 0분에 일어나도록 하였고, CLP2군은 16분에 일어나도록 하였다. 문맥으로 유출되는 췌장의 effluent액에서 인슐린과 글루카곤 농도를 RIA법으로 측정하였고 호르몬의 분비 속도를 산출하여 분비동태 양상을 분석하였다. 결과에서 인슐린 분비량은 GLP1군에서 가장 낮아서 cephalic glucopenia에 의하여 다소 감소하는 경향이었으나, 세 군간에 통계적으로 유의적인 차이는 없었다. 인슐린의 분비동태 양상을 살펴보면 이봉성의 정규 양상을 보였으나, GLP1군에서 첫번째 peak (4 min)가 다소 둔화되는 현상을 보였다. 글루카곤의 분비동태 양상도 이봉성의 정규 양상을 보였으며, 특히 GLP1군에 있어서 0~15분간의 글루카곤 분비량은 cephalic glucopenia에 의하여 유의성 있게 (p<0.05) 증가하였다. GLP2군에 있어서 글루카곤 분비량은 관류 후 15~30분 사이에 중가하는 경향을 볼 수 있었으나 통계적인 유의성은 없었다. 따라서 頭部의 포도당 결핍은 글루카곤의 분비를 증가시키는 것으로 나타났고, 이러한 현상은 특히 관류의 early period에서 현저하였다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제19권3호
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• pp.311-318
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• 1997

Ludwig's angina has been defined as a potentially lethal, rapidly spreading cellulitis, involving the sublingual and submandibular spaces, and is manifesed by a brawny, suprahyoid induration, tender swelling in the floor of mouth, elevation and posterior displacement of tongue. This paper is of interest not only because of severity of infection but also because of associated diabetic mellitus. Diabetes mellitus is a complex syndrome of disordered metabolism and elevated blood glucose, it results from deficiency of insulin secretion of combination of insulin resistance and inadequate insulin secretion. The effects of diabetic mellitus include neuropathy, vascular insufficiency, decreased leukocytic function, hematologic change etc. Clinically this may be refelected by the increased severity of infections seen in diabetics. The treatment of infections in diabetics are reduction of number of microbes through the use of appropriated antimicrobial agents and proper surgical drainage and improvement of the host factors by tight control of insulin replacement and immediate intervention to correct abnormalities of the local factors by drainage, debriment, and removal of avoidance of foreign bodies. The authors present the report of the Ludwig's angina in patient with diabetic mellitus, with literature review and good clinical result.

• Laboraroty Animal Research
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• 제34권4호
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• pp.140-146
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• 2018

Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance. As consistent, numerous studies have reported alteration of bile acid signaling pathways in type II diabetes patients. Interestingly, bile acids have shown to activate TGR5 in intestinal L cells and enhance secretion of glucagon-like peptide 1 (GLP-1) to potentiate insulin secretion in response to glucose. Moreover, FXR has been shown to crosstalk with TGR5 to control GLP-1 secretion. Altogether, bile acid receptors, FXR and TGR5 are potent therapeutic targets for the treatment of metabolic diseases, including type II diabetes.