• KSBB Journal
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• 제21권6호
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• pp.466-473
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• 2006

본 연구에서는 췌장 베타세포의 인슐린 분비 촉진 물질로 선별된 방선균 배양액에서 유래한 YHB-2017 (genistein)의 인슐린 분비 촉진 활성의 특성을 조사하고 그 작용 기전을 밝히고자 하였다. YHB-2017는 췌장소도에서 glucose 농도가 16 mM일 때 농도 의존적으로 인슐린 분비를 대조군에 비해 2배 이상 촉진시켰으며, 5.5 mM 이하의 glucose 농도에서는 인슐린 분비 촉진 활성이 거의 없는 것으로 나타났다. MIN6 세포를 이용한 YHB-2017의 인슐린 분비 촉진 활성 특성을 분석한 결과, PKA inhibitor (H89)에 의해서 활성이 저해되었으며, 세포막의 $K_{ATP}$ channel를 배제하고 단순히 칼슘이온을 최대로 세포내로 유입시킨 조건인 diazoxide ($200\;{mu}M$)와 KCI (35 mM)를 첨가한 경우에 YHB-2017는 인슐린 분비 촉진 활성을 나타내 $K_{ATP}$ channel-independent pathway를 통한 인슐린 분비 촉진 기전을 추정할 수 있었다. 베타세포의 단백질 인산화에 대한 영향을 조사한 결과 YHB-2017는 고농도 glucose 조건에서만 PKA 기질과 cAMP response element-binding protein (CREB)의 인산화를 증가시키는 것으로 나타났고, PKC 기질의 인산화에는 영향이 없었다. 또한, YHB-2017를 18시간동안 베타세포에 처리하였으나 인슐린 유전자 발현에는 영향을 주지 않았다. 이상의 결과를 종합하여 볼 때 YHB-2017는 기존의 sulphonylurea 계열 약물과는 다른 작용 기전에 의해 췌장 베타세포에서 인슐린 분비를 촉진시키며, 그 기전은 PKA경로를 통해 amplify 신호를 활성화시키는데 관여하는 것으로 추정된다.

• 생명과학회지
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• 제27권3호
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• pp.289-294
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• 2017

삼채(Allium species)는 전통적인 약재나 건강 증진 식품으로 사용되어 왔다. 특히, Allium hookeri (A. hookeri)는 제 2형 당뇨병 모델 마우스에서 혈당 감소 효과가 보고되었다. 본 연구에서는 A. hookeri 추출물이 3T3-L1 세포에서 인슐린 민감성을 증진시키는지 시험하였다. 3T3-L1 지방세포분화가 불완전하게 유도되는 저농도의 인슐린 조건에서, A. hookeri 추출물은 세포 내 지방 함량을 증가시키고, 분화 유도 전사인자인 $PPAR{\gamma}$의 발현을 상승시켰다. 또한, A. hookeri 추출물은 포도당 수송체 4(GLUT4)의 발현을 증가시킴으로써 세포 내 포도당 흡수(glucose uptake)를 향상시켰다. 이러한 결과들은 A. hookeri 추출물이 인슐린 민감성을 증진시켜 $PPAR{\gamma}$와 GLUT4를 활성화하고, 세포 내 포도당 흡수를 촉진한다는 사실을 보여준다. 따라서, A. hookeri 추출물은 당뇨병의 예방 및 치료에 임상적으로 응용될 수 있을 것으로 생각된다.

• 한국축산시설환경학회지
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• 제3권1호
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• pp.1-12
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• 1997

This study was conducted to investigate the combined effects of VFA composition of rumen fluid and heat exposure (30${\pm}$2$^{\circ}C$) on the general clinical view and insulin secretory response to glucose in sheep. The total infusion of nutrients was examined in sheep via the technique of continuous alimentation. Four adult Suffolk sheep fitted with a permanent ruminal cannula and a simple T-shaped duodenal cannula were used. A peristaltic pump was used to infuse the solutions of volatile fatty acid triglycerides (VFA-TG) consisting of 70 triacetin : 20 tripropionin : 10 tributyrin (low propionin division: LP) and 50 triacetin : 40 tripropionin : 10 tributyrin (high propionin division: HP) on the basis of energy and minerals into the rumen, and casein solution into the duodenum. The effects of heat exposure and type of the levels of VFA-TG solutions on the insulin secretory response to glucose in sheep were investigated by using hyperglycemic clamp (HGC) technique. The results obtained are summarized as follows: 1. During the heat exposure (latter half of the infusion period), respiration rate, heart rate and rectal temperature increased (P＜0.01, P＜0.01, P＜0.05), but the levels of VFA-TG solutions (LP and HP division) did not affect the general clinical view except for the heart rate. 2. In the HGC technique, glucose infusion rate (GIR) and mean plasma insulin increments (MPII) tended to be ower in the heat exposure than in the thermoneutral environment, but no significant difference was found among the treatments. GIR and MPII remained unchanged between the levels of VFA-TG solutions. 3. In the HGC technique, ratio of MPII to GIR (MPII/GIR) which represents pancreatic ${\beta}$-cell response to glucose stimulation remained unchanged among the treatments.

• 대한한의학회지
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• 제31권4호
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• pp.79-100
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• 2010

Objective: Production of ROS from glucose toxicity results in injury of pancreatic $\beta$-cells in diabetes models. This study was undertaken to examine the influence of Lespedeza Cuneata extract (LCE) on cytoprotective effects on glucose toxicity, insulin secretion and gene expression in RIN-m5F cells. Methods: First, we measured LCE's antioxidant activity by DPPH free radical-scavenging activity and SOD activity. After the various concentrations of LCE were added to the RIN-m5F cells, we measured cell viability with glucose stimulation by MTT assay and glucose-stimulated insulin secretion. We analyzed gene expression with Agilent whole mouse genome 44K oligo DNA microarray and searched for related pathways in KEGG (Kyoto Encyclopedia of Genes and Genomes). Lastly we measured INS-1, INS-2, INS-R, IRS-1, IRS-2, IRS-3, GLP-1R, and GLP-2R mRNA expression by real time RT-PCR. Results: Free radical-scavenging activity, SOD activity and insulin secretion increased dependent on LCE concentration, but LCE did not show considerable cytoprotective effect on RIN-m5F cells. More than twice expressed gene was 6362 in Oligo DNA chip. In KEGG, the most related pathway was the metabolic pathway. In the insulin signaling pathway, up expressed genes were Irs1, Mapk8, Akt1, and Lipe and down expressed genes were Rhoq, Fbp2, Prkar2b, Gck, and Prkag1. In real time RT-PCR, IRS-2, and IRS-3 expression increased significantly compared to the control group on LCE $12{\mu}g/m{\ell}$ concentration and GCK expression decreased significantly compared to the control group. Conclusions: These results show that LCE encourages insulin secretion and insulin metabolism by complicated gene mechanisms. Further mechanism study and clinical study seem to be necessary about Lespedeza Cuneata.

• Clinical and Experimental Pediatrics
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• 제61권7호
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• pp.217-220
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• 2018

Purpose: Type 1 diabetes mellitus (T1DM) is a chronic and immune-mediated disease, which is characterized by the progressive destruction of pancreatic beta cells. T1DM precipitates in genetically susceptible individuals through environmental factors. In this study, we aimed to evaluate the impact of autoimmunity and intestinal colonization of Candida albicans on the development of T1DM. Methods: Forty-two patients newly diagnosed with T1DM and 42 healthy subjects were included in this monocentric study. The basic and clinical characteristics of the patients were recorded. T1DM-, thyroid-, and celiac-associated antibodies were evaluated. Stool cultures for C. albicans were performed to assess whether or not gut integrity was impaired in patients with T1DM. Results: The evaluation of T1DM- and thyroid-associated antibodies showed that the prevalences of islet cell antibodies and antithyroperoxidase positivity were higher in the study patients than in the patients in the control group. Furthermore, the direct examination and culture of fresh stool samples revealed that 50% of the patients with T1DM and 23.8% of the control subjects had fungi (C. albicans). Conclusion: Through this study, we suggest that the presence of intestinal C. albicans colonization at the time of the diagnosis of T1DM may indicate impairment of normal intestinal microbiota. We also suggest that there may be a tendency of T1DM in patients with a high prevalence of intestinal C. albicans.

• Nutritional Sciences
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• 제8권2호
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• pp.111-117
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• 2005

It has been more than three decades since the first assay assessing circulating 25 (OH)D in human subjects was performed That publication as well as several that followed it defined 'normal' nutritional vitamin D status in human populations. Recently, the wisdom by which 'normal' circulating 25 (OH)D levels in human subjects were assigned in the past has come under question. It appears that sampling human subjects, who appear to be free from disease, and assessing 'normal' circulating 25 (OH)D levels by plotting a Gaussian distribution is grossly inaccurate. There are many reasons why this method is inaccurate, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary recommendations for vitamin D. For instance, a 400 IU/day. AI for vitamin D is insignificant when one considers that a 10-15 minute whole body exposure to peak summer sun will generate and release up to 20,000 IU vitamin $D_3$ into the circulation. Recent studies, which orally administered up to 10,000 IU/day vitamin $D_3$ to human subjects for several months, have successfully elevated circulating 25 (OH)D levels to those observed in individuals from sun-rich environments. Further, we are now able to accurately assess sufficient circulating 25 (OH)D levels utilizing specific biomarkers instead of guessing what an adequate level is. These biomarkers include intact parathyroid hormone (PTH), calcium absorption, bone mineral density (BMD), insulin resistance and pancreatic beta cell function. Using the data from these biomarkers, vitamin D deficiency should be defined as circulating levels of 25 (OH)D$\leq$30 ng/mL. In certain cases, such as pregnancy and lactation, significantly higher circulating 25 (OH)D levels would almost certainly be beneficial to both the mother and recipient fetus/infant.

• 한국영양학회:학술대회논문집
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• 한국영양학회 2004년도 추계학술대회
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• pp.22-33
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• 2004

It has been more than three decades since the first assay assessing circulating 25(OH)D in human subjects was performed. That publication as well as several that followed it defined 'normal' nutritional vitamin D status in human populations. Recently, the wisdom by which 'normal' circulating 25(OH)D levels in human subjects were assigned in the past has come under question. It appears that sampling human subjects, who appear to be free from disease, and assessing 'normal' circulating 25(OH)D levels by plotting a Gaussian distribution is grossly inaccurate. There are many reasons why this method is inaccurate, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary recommendations for vitamin D. For instance, a 400IU/day. AI for vitamin D is insignificant when one considers that a 10-15 minute whole body exposure to peak summer sun will generate and release up to 20,000 IU vitamin $D_3$ into the circulation. Recent studies, which orally administered up to 10,000 IU/day vitamin $D_3$ to human subjects for several months, have successfully elevated circulating 25(OH)D levels to those observed in individuals from sun-rich environments. Further, we are now able to accurately assess sufficient circulating 25(OH)D levels utilizing specific biomarkers instead of guessing what an adequate level is. These biomarkers include intact parathyroid hormone (PTH), calcium absorption, bone mineral density (BMD), insulin resistance and pancreatic beta cell function. Using the data from these biomarkers, vitamin D deficiency should be defined as circulating levels of $25(OH)D{\leq}30ng/mL$. In certain cases, such as pregnancy and lactation, significantly higher circulating 25(OH)D levels would almost certainly be beneficial to both the mother and recipient fetus/infant.

• 동의생리병리학회지
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• 제25권3호
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• pp.389-397
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• 2011

This study tried to integrate the traditional oriental medical theories and results of experimental studies of herbaceous plants on anti-diabetes. And I tried to analyze recent experimental study trend on the anti-diabetic herb. I searched anti-diabetic herb studies on 4 korean databases and 10 korean journals by keywords, 'diabetes', 'blood glucose', 'glycometabolism', 'pancreatic ${\beta}$-cell', etc. In order to see detail review, searching was performed from 2000 to 2010. And I searched 125 study cases concerning anti-diabetic herb and 72 varieties herbaceous plants used in study of anti-diabetes. and I analyzed the choice motives of each herb for anti-diabetic study, the extract methods and anti-diabetic evaluation contents. And I analyzed anti-diabetic herbs from a traditional oriental medical point of view. When the researchers chose herb for anti-diabetic experiment, just 8.8% of the choice was based on the oriental medical evidences. I found that 60.6% of the herb shown to be effective in diabetes experimentally had oriental medical theory-based Properties(性). There were studies with whole plants(16.8%), aqueous extract(45.6%), methanol extract(8.0%), ethanol extract(8.0%) and comparative studies of more than 2 types of extracts or various fractions(18.4%). The most frequent experimental diabetic models was diabetic mouse induced by streptozotocin(STZ)(87.8%). And there were db/db mouse(6.7%), ob/ob mouse(1.1%), etc. 33.6% of all studies just measured hematological indices of diabetes, and 66.4% researches analyzed details. To improve herbaceous plants study on diabetes, we oriental medical scientists have to integrate the oriental medical theories and results of experimental studies.

• 약학회지
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• 제55권4호
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• pp.301-308
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• 2011

Diabetes has been one of major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has been focused as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK increases glucose uptake through independent insulin signal pathway. In this study, we investigated the anti-diabetic effect of Angelica gigas Nakai extract (AGNEX), a mixture of decursin and decursinol angelate (53 : 47), decursin and decursinol angelate on blood glucose, glucose transport (GLUT) and AMPK expression levels in streptozotocin (STZ)-induced diabetic rats. To induce diabetes, 50 mg/kg of STZ was injected via i.v. route and AGNEX 2 mg/kg (STZ+AG), decursin 2 mg/kg (STZ+D), decursinol angelate 2 mg/kg (STZ+DA), and metformin 100 mg/kg (STZ+M) were administered orally for 21 days. STZ+DA group showed a significant decrease in fasting blood glucose levels compared to the other groups. Decursinol angelate significantly upregulated expression of glucose transporter 4 (GLUT4) and phosphorylation of AMPK (p-AMPK) in skeletal muscle of rats. In pancreas of rats, decursinol angelate significantly increased expression of GLUT2 through down-regulation of p-AMPK. In addition to the result of pancreatic islets morphology, AGNEX, decursin, decursinol angelate, and metformin treated group recovered ${\beta}$-cell damage by hyperglycemia. These results indicate that decursinol angelate might be a potential anti-diabetic agent and AGNEX could be useful in the treatment of diabetes mellitus.

• 대한약침학회지
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• 제20권4호
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• pp.235-242
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• 2017

Irisin is a novel hormone like polypeptide that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5), a membrane-spanning protein and which is highly expressed in skeletal muscle, heart, adipose tissue, and liver. Since its discovery in 2012, it has been the subject of many researches due to its potent physiological role. It is believed that understanding irisin's function may be the key to comprehend many diseases and their development. Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Irisin is a powerful messenger, sending the signal to determine the function of specific cells, like skeletal muscle, liver, pancreas, heart, fat and the brain. The action of irisin on different targeted tissues or organs in human being has revealed its physiological functions for promoting health or executing the regulation of variety of metabolic diseases. Numerous studies focus on the association of irisin with metabolic diseases which has gained great interest as a potential new target to combat type 2 diabetes mellitus and insulin resistance. Irisin is found to improve insulin resistance and type 2 diabetes by increasing sensitization of the insulin receptor in skeletal muscle and heart by improving hepatic glucose and lipid metabolism, promoting pancreatic ${\beta}$ cell functions, and transforming white adipose tissue to brown adipose tissue. This review is a thoughtful attempt to summarize the current knowledge of irisin and its effective role in mediating metabolic dysfunctions in insulin resistance and type 2 diabetes mellitus.