• 대한약리학회지
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• 제31권1호
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• pp.135-140
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• 1995

Glycation이란 단당류의 카보릴기와 아미노산의 입실론 아미노기가 공유결합에 의하여 형성되는 반응으로 이는 단백질의 생리적 기능을 변화시키며 아울러 당뇨합병증을 유발한다. 본 연구에서는 warfarin과 dansylsarcosine의 단백질결합에 미치는 glycation의 영향을 평형투석법을 이용하여 연구하였으며 평형투석은 섭씨 37도의 진탕수조에서 3시간 동안 실시하였다. 약물의 농도가 알부민의 농도보다 높을 경우, $50{\pm}16%$가 glycation된 알부민은 $8.5{\pm}5.28%$ glycation 알부민을 함유한 정상알부민에 비해 약물과의 결합도가 낮았으나 warfarin의 농도가 알부민의 3배가 될 경우에만 유의성이 인정되었고(P<0.05) 6%의 차이를 보였다. 본 실험에 나타난 glycation에 의한 유리약물의 미미한 상승효과는 glycated albumin 농도가 낮은 생체내의 여건과, 실제로 사용되는 약물의 적정 치료농도가 낮고 또한 과도한 유리약물은 신장을 통하여 신속히 배설되는 이유로 당뇨환자의 신기능 손상이 없는한 glycation에 의한 유리약물의 상승은 약물중독의 위험요소로 작용되지 않으리라 생각된다.

• 분석과학
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• 제36권1호
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• pp.12-21
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• 2023

Protein glycation is vital to aging and disease. However, glycated proteins are low-abundant in plasma, rendering them difficult to identify using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Many studies have analyzed glycated peptides with high reproducibility. Here, glycated peptides in human serum were analyzed by LC-MS/MS using data-dependent acquisition (DDA) and parallel reaction monitoring (PRM). Boronic acid (BA) enrichment of in vitro glycated human serum peptides was performed. BA enrichment identified the most glycated peptides, and the glycated peptides of the more diversified proteins, excluding albumin, were analyzed. In PRM, glycated albumin PSMs were the most common, and this method exhibited the best reproducibility. The results of this study could help compare methods for identifying glycation-related biomarkers.

• 생명과학회지
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• 제21권1호
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• pp.36-43
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• 2011

Glycate화된 단백질이 혈관질환의 발생에 관여하는지 알아보기 위하여 glycated albumin (GA)이 혈관평활근 세포에서 인터루킨-6 발현에 영향을 주는지 조사하고 또한 그 기전을 구명하였다. GA에 노출된 혈관평활근세포에서 인터루킨-6 transcript가 증가하고, 인터루킨-6 단백질의 분비가 증가하고, 또한 인터루킨-6 유전자의 promoter가 활성화되었다. GA에 의한 인터루킨-6 유전자의 promoter 활성화는 dominant negative 형태의 Toll-like receptor (TLR)-4와 myeloid differentiation factor 88 (Myd88)에 의하여 크게 감소되었지만, dominant negative 형태의 TLR-2와 TIR-domain-containing adapter-inducing interferon-$\beta$ (TRIF)의 영향을 받지 않았다. 그리고 Extrcellular signal-related kinase (ERK) 억제 물질들은 GA에 의한 인터루킨-6의 분비 및 인터루킨-6 유전자 promoter 활성화를 억제하였다. 그리고 인터루킨-6 유전자의 promoter의 NF-${\kappa}B$-binding sequence에 변이는 GA에 의한 인터루킨-6 유전자의 promoter 활성화 억제하였다. 이러한 결과는 혈관평활근세포에서 GA에 의한 인터루킨-6 유전자 활성화에 TLR-4와 ERK 및 NF-${\kappa}B$가 관여함을 의미한다.

• BMB Reports
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• 제41권7호
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• pp.516-522
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• 2008

The glycation of BSA leads to protein/peptide modifications that result in the formation of AGEs. AGEs react with the amino groups of N-terminal amino acid residues, particularly arginine and lysine residues. Enhanced AGE formation exists in the blood and tissues of diabetics, as well as in aging and other disorders. The Identification of AGEs is of great importance. Mass spectrometry has been applied to identify and structurally elucidate AGEs. Here, we report on the identification of AGE-peptides and AGE precursors based on relative mass changes as a result of specific AGE formation. HPLC-ESIMS, ESI-MS/MS, and the Mascot database were used. The relative mass changes due to the specific type of AGE formation were added to the identified peptides followed by a manual search of the glycated samples, which resulted in the identification of seven peptides for the formation of five AGEs, namely CML, pyrraline, imidazolone A, imidazolone B, and AFGP. Four glycated peptides (FPK, ECCDKPLLEK, IETMR, and HLVDEPQNLIK) were identified in the formation of AGE-precursors.

• Journal of Nutrition and Health
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• 제27권10호
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• pp.1048-1057
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• 1994

Nonobese NIDDM patients were studied were studied with respect to changes in visceral protein status, serum glucose and lipids and insulin secretion capacity before and after intake of enteral formula. Patients with renal or hepatic disease, gastrectomy, malabsorption, weight gain over past 6 months and poorly controlled blood glucose level were excluded. Eighteen patients served as case and administered, in addition of their usual diet, 400ml of enteral formula for 8 weeks. Another 18 patients participated in controls and had usual food intake for 8 weeks. In the begining, the levels of fasting and postprandial glucose, glycated hemoglobin, triglyceride, HDL, LDL, total cholesterol, albumin, total protein and transferrin and glucose response area on oral glucose tolerance test were not different between two groups. The response areas of insulin, C-peptide and free fatty acid and serum IGF-1 level were higher in the case than in the control group. Energy intake of patients given enteral formula exceeded their estimated energy requirements(108%) and they consumed a mean of 112g protein per day. Patients given enteral formula showed an increase in body weight(4.4%), serum transferrin(10%), IGF-1(13%) and triglyceride(34%) while controls showed no changes in those parameters at 8 weeks compared to initial values. There were no significant changes after 8 weeks in the levels of glucose, glycated hemoglobin, HDL, LDL, total cholesterol, total protein and albumin and response areas of glucose, insulin, C-peptide and free fatty acid in both groups compared to initial values. This study suggests that nutrition supplement with enteral formula can increase body weight and visceral protein status in nonobese NIDDM patients without changes in blood glucose. However, excessive calorie intake could temporarily increase serum triglyceride. In addition, this study indicates that serum transferrin and IGF-1 are more sensitive indicators to changes of protein intake than serum albumin and total protein.

• 한국콘텐츠학회논문지
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• 제15권3호
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• pp.272-279
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• 2015

최근 혈당조절에 도움이 되는 다양한 천연추출물에 대한 연구가 진행되고 있다. 귀리는 다양한 생리효능이 있는 것으로 알려져 있는데 특히 ${\beta}$ 클루칸은 체내 혈중 콜레스테롤 수치를 낮추어 심혈관 질환을 예방하고 비만과 관련된 성인병 예방에 효과를 보이는 것으로 보고되고 있다. 이에 본 연구는 상품화된 귀리 추출물로 이루어진 다운앤컨트롤(비엠제약)을 이용하여 6주간 무작위, 이중맹검, 실험군-대조군 임상 연구를 통해 혈당 및 혈중 콜레스테롤에 대한 효과를 평가한 결과, 통계학적으로 유의한 차이를 보이지는 않았지만 당화알부민은 각각 시험군에서 50.33% 감소, 대조군에서 37.91% 감소 및 중성지방은 시험군에서 7.51% 감소, 대조군에서 3.98% 증가로 상대적으로 차이를 보여 시험약의 혈당저하 효과 및 중성지방의 감소효과를 일부에서 관찰할 수 있었다.

• 대한중풍순환신경학회지
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• 제21권1호
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• pp.11-20
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• 2020

■ Objectives The purpose of this study is to report on a case that showed improvement in type 2 diabetic patients by using herbal medicine, Yeoldahansotang-gami. ■ Methods Yeoldahansotang-gami was given to patients with type 2 diabetes for 71days. To evaluate the effect, blood glucose was measured 4 times a day. As measured blood sugar, the frequency of hyperglycemia, changes in fasting blood sugar, changes in postprandial blood sugar, and changes in glucose variability were analyzed. The patient's insulin injection dose change was observed, and HbA1c and glycated albumin were measured. Follow-up was performed for 7 months to observe whether the treatment effect was maintained. ■ Results During treatment, the patient's blood sugar control, glucose variability, and HbA1c were improved, and insulin injection dose was gradually reduced and stopped. HbA1c and glycated albumin levels maintained improvement without insulin injection during the follow-up period. ■ Conclusion This study showed the effect of yeoldahansotang-gami on type 2 diabetes patient.

• Natural Product Sciences
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• 제27권1호
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• pp.28-35
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• 2021

The aim of this study was to anatomize the therapeutic potential of alaternin (=7-hydroxyemodin) against inflammation, advanced glycation end products (AGEs) formation, tyrosinase, and two cyclin-dependent kinases (CDKs), CDK2 and CDK4, and compare its potency with emodin. Alaternin showed lower cytotoxicity and higher dose-dependent inhibition against lipopolysaccharide (LPS) induced nitric oxide (NO) production with half maximal inhibitory concentration (IC50) of 18.68 µM. Similarly, alaternin efficaciously inhibited biotransformation of fluorescent AGEs and amyloid cross-β structure on the bovine serum albumin (BSA)-glucose-fructose system, five times more than emodin. Interestingly, alaternin also showed selective activity against CDK4 at 170 µM, whereas emodin inhibited both CDK2 and CDK4 at a concentration of 17 and 380 µM respectively. In addition, alaternin showed dose-dependent inhibitory activity against mushroom tyrosinase with inhibition percentage of 35.84 % at 400 µM. Altogether, alaternin with pronounced inhibition against inflammatory mediator (NO), glycated products formation, and targeted inhibition towards CDK4 receptor can be taken as an important candidate to target multiple diseases.

• Journal of Nutrition and Health
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• 제27권8호
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• pp.805-818
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• 1994

This study investigated the effect of enteral nutrition supplementation on glucose and lipid metabolism in non-insulin dependent diabetes mellitus(NIDDM) patients(n=29). Nutrition formula(400kcal/day) were supplied daily for eight weeks as a substitute for a snack or a meal. Subjects were divided into three groups based on changes of fasting blood glucose(FBG), glucose response area(GRA) on oral glucose tolerance test(OGTT), before and after intake of nutrition formula : group 1(the group of a decrease in FBG and GRA, n=20), group 2(the group of a decrease in FBG and an increase in GRA, n=4), and group 3(the group of an increase in FBF and GRA, n=5). Before nutrition supplementation, group 3 showed a longer tendency of DM duration and a lower tendency of insulin and C-peptide response are than those of group 1 and 2. At 8 weeks after nutrition supplementation, group 1 showed a significant increase in insulin and C-peptide response areas but group 2 and 3 showed no change in those areas. After nutrition supplementation, all three groups showed a tendency of decrease in glycated hemoglobin and no significant changes in the levels of serum triglycerides, HDL, LDL, total cholesterol, albumin, transferrin, creatinine, GOT and GPT. The results suggest that using an enteral nutrition formula in NIDDM patients is a good substitute for a meal or snack and could improve blood glucose control without any changes in lipid levels, and liver and kidney functions. The beneficial effect of nutrition supplementation on glycemic control resulted from components of nutrition formula had such as additional fiber and high monounsaturated fatty acid as the source of fat to be helpful 세 glycemic control in diabetics.

• The Korean Journal of Physiology and Pharmacology
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• 제15권5호
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• pp.299-305
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• 2011

Calcineurin (CaN) is activated in diabetes and plays a role in glomerular hypertrophy and extracellular matrix (ECM) accumulation. Here, kidneys from diabetic model mice were investigated for the expression of the regulator of CaN 1 (RCAN1) isoform 4 (RCAN1.4) which had been shown to be transcriptionally upregulated by CaN activation. We found the increased immunoreactivity for RCAN1 in the glomerular cells of db/db mice and streptozotocin-induced diabetic mice. In concordance, the expression of RCAN1 protein and RCAN1.4 mRNA were elevated in the whole kidney sample from db/db mice. Interleukin-$1{\beta}$ (IL-$1{\beta}$), tumor necrosis factor-${\alpha}$, and glycated albumin (AGE-BSA) were identified as inducers of RCAN1.4 in mesangial cells. Pretreatment of cyclosporine A blocked the increases of RCAN1.4 stimulated by IL-$1{\beta}$ or AGE-BSA, suggesting that activation of CaN is required for the RCAN1.4 induction. Stable transfection of RCAN1.4 in Mes-13 mesangial cells upregulated several factors relevant to ECM production and degradation. These results suggested that RCAN1.4 might act as a link between CaN activation and ECM turnover in diabetic nephropathy.