• BMB Reports
• /
• 제33권2호
• /
• pp.148-154
• /
• 2000

The glycation process plays an important role in accelerated atherosclerosis in diabetes, and the uptake of atherogenic lipoproteins by macrophage in the intima of the vessel wall leads to foam cell formation, an early sign of atherosclerosis. Besides the lipolytic action on the plasma triglyceride component, lipoprotein lipase (LPL) has been reported to enhance the cholesterol uptake by arterial wall cells. In this study, some properties of LPL-mediated low-density lipoprotein (LDL) uptake and the effect of LDL glycation were investigated in RAW 264.7 cell, a murine macrophage cell line. In the presence of LPL, $^{125}I$-LDL binding to RAW 264.7 cells was increased in a dose-dependent manner. At concentrations greater than $20\;{\mu}g/ml$ of LPL, LPL-mediated LDL binding was increased about 17-fold, achieving saturation. Without LPL, both very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) were ineffective in blocking the binding of $^{125}I$-LDL to Cells. However, LPL-enhanced LDL binding was inhibited about 50% by the presence of VLDL, while no significant effect was observed with HDL. Heat inactivation of LPL caused a 30% decrease of LDL binding. In the presence of LPL, the cells took up 40% of cell-bound native LDL. No significant difference was observed in cell binding between native and glycated LDL. However, the uptake of glycated LDL was significantly greater than that of native LDL, reaching to 70% of the total cell bound glycated LDL. These results indicate that LPL can cause the significant enhancement of LDL uptake by RAW 264.7 cells and the enhanced uptake of glycated LDL in the presence of LPL might play an important role in the accelerated atherogenesis in diabetic patients.

• Molecules and Cells
• /
• 제19권1호
• /
• pp.60-66
• /
• 2005

Low density lipoproteins (LDL) play important roles in the pathogenesis of atherosclerosis. Diabetes is associated with accelerated atherosclerosis leading to cardiovascular disease in diabetic patients. Although LDL stimulates the proliferation of arterial smooth muscle cells (SMC), the mechanisms are not fully understood. We examined the effects of native LDL and glycated LDL on the extracellular signal-regulated kinase (ERK) pathway. Addition of native and glycated LDL to rat aorta SMCs (RASMCs) stimulated ERK phosphorylation. ERK phosphorylation was not affected by exposure to the $Ca^{2+}$ chelator BAPTA-AM but inhibition of protein kinase C (PKC) with GF109203X, inhibition of Src kinase with PP1 ($5{\mu}M$) and inhibition of phospholipase C (PLC) with U73122/U73343 ($5{\mu}M$) all reduced ERK phosphorylation in response to glycated LDL. In addition, pretreatment of the RASMCs with a cell-permeable mitogen-activated protein kinase kinase (MEK) inhibitor (PD98059, $5{\mu}M$) markedly decreased ERK phosphorylation in response to native and glycated LDL. These findings indicate that ERK phosphorylation in response to glycated LDL involves the activation of PKC, PLC, and MEK, but is independent of intracellular $Ca^{2+}$.

• Preventive Nutrition and Food Science
• /
• 제1권1호
• /
• pp.134-142
• /
• 1996

Diabetes carries an increased risk of atherosclerotic disease that is not fully explained by known car-diovascular risk factors. There is accumulating evidence that advanced glycation of structural proteins, and oxidation and glycation of circulating lipoproteins, are implicated in the pathogenesis of diabetic ather-osclerosis. Reactions involving glycation and oxidation of proteins and lipids are believed to contribute to atherogenesis. Glycation, the nonenzymatic binding of glucose to protein molecules, can increase the ather-ogenic potential of certain plasma constituents, including low density lipoptotein(LDL). Glycation of LDL is significant increased in diabetic patients compared with normal subjects, even in the presence of good glycemic control. Metabolic abnormalities associated with glycation of LDL include diminished recognition of LDL by the classic LDL receptor; increased covalent binding of LDL in vessel walls ; enhanced uptake of LDL by the macrophages, thus stimulating foam cell formation ; increased platelet aggregation; formation of LDL-immune complexes ; and generation of oxygen free radicals, resulting on oxidative damage to both the lipid and protein components of LDL and to any nearby macromolecules. Oxidized lipoproteins are characterzied by cytotoxicity, potent stimulation of foam cell formation by macrophages, and procoagulant effects. Combined glycation and oxidation, "glycoxidation" occurs when oxidative reactions affect the initial products of glycation, and results in irreversible structural alterations of proteins. Glycoxidation is of greatest significance in long lived proteins such as collagen. In these proteins, glycoxidation products, believed to be atherogenic, accumulate with advancing age : in diabetes, their rate of accumulate is accelerated. Inhibition of glycation, oxidation and glycoxidation may form the basis of future antiaterogenic strategies in both diabetic and nondiabetic individuals.dividuals.

• Journal of Nutrition and Health
• /
• 제30권7호
• /
• pp.781-788
• /
• 1997

This present study was undertaken to evaluate the effects of 5 % chicory extract on serum glucose and lipid metabolism in diabetic rats treated with streptozotocin (STZ). The experimental subjects were divided into 4 groups. : No-fiber , cellulose, insulin, and chicorygroup. The animals were fed ad libitum each of the experimental diets for 4 weeks. The food intake and food efficiency ratio in chicory group was significantly higher than in no-fiber, cellulose, and inulin groups. The reduction of body weight was also significantly lower. The wet weights of cecum and cecal contents were significantly increased in rat fed chicory extract. Total glycated hemoglobin was significantly decreased by chicory extract feeding whereas serum total cholesterol . LDL-choelsterol, and HDL-choelsterol levels were significantly increased. But there were no differences between HDL-choesterol/total cholesterol ratios, LDL-cholesterol/HDL-cholesterol ratios, and atherogenic index. After 10 -hour fast, the levels of hepatic triglyceride and phospholipid were significantly higher in the chicory group than any in other groups. These results indicated that chicory extract is an effective therapeutic regimen for control of metabolic deragements in diabetics.

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

• 한국산학기술학회논문지
• /
• 제21권8호
• /
• pp.348-358
• /
• 2020

이압요법은 보완·대체요법 중 하나로 귀를 인체의 축소판으로 보고 인체와 상응하는 귀 반응구역(점)에 자극을 주어 해당 장기의 증상 완화 및 치료 효과를 기대하는 중재법을 말한다. 본 연구에서는 이압요법이 제2형 당뇨병 노인의 혈당, 당화혈색소 및 혈중지질에 미치는 효과 알아보기 위해 시행한 연구이다. 본 연구는 무작위 배정, 단일 맹검, 플라세보 대조군 비교 설계를 이용한 실험연구로 자료수집은 2018년 3월 16일부터 2018년 5월 11일까지 이루어졌다. 제2형 당뇨병 노인을 실험군, 대조군에 각각 22명씩 배정하였다. 실험군은 당뇨병과 관련 있는 귀 반응구역(점)에 이압요법을 실시하였고, 대조군은 플라세보 이압요법을 실시하였다. 중재 효과를 확인하기 위해 매주 식후 2시간 혈당을 측정하였으며 사전 및 사후조사로 당화혈색소 및 혈중지질(중성지방, LDL 콜레스테롤, HDL 콜레스테롤)을 측정하였다. 본 연구결과 제2형 당뇨병 노인에게 이압요법을 적용하여 실험 전부터 실험 후까지 7회에 걸쳐 측정한 혈당은 그룹과 시간 경과의 상호작용이 유의한 것으로 나타났다(p=.030). 또한, 6주간의 이압요법 적용 후 실험군 내에서 당화혈색소는 유의하게 감소하였으나(t=-2.44, p=.024) 그룹 간 차이는 유의하지 않았고 중성지방, LDL 콜레스테롤, HDL 콜레스테롤 수치는 실험 전과 비교하여 두 그룹 간 통계적으로 유의한 차이가 없었다. 본 연구에서 시행한 6주간의 이압요법은 제2형 당뇨병 노인의 식후혈당 및 당화혈색소를 감소시키는 효과가 있는 것으로 나타났다. 따라서 이압요법은 임상현장에서 제2형 당뇨병 노인의 혈당 조절에 효과가 검증된 중재 요법으로 활용될 수 있을 것으로 보인다.

• Journal of Nutrition and Health
• /
• 제42권2호
• /
• pp.107-118
• /
• 2009

In patients with type 2 diabetes, oxidative stress could be increased by their metabolic changes. Elevated plasma homocysteine is considered as one of markers of enhanced oxidative stress. Due to oxidative stress, some complications like cardiovascular or renal diseases may develop in type 2 diabetes patients. Plasma homocysteine concentration may be increased if folate status were inadequate. Protective effects against oxidative stress may be diminished if the status of anti-oxidative nutrient as vitamin C was poor. It is, therefore, important to maintain adequate status of folate and vitamin C in type 2 diabetes patients. Thus, this study was performed to determine the effects of supplementation of folate and/or ascorbate on blood glycated hemoglobin ($HbA_{1c}$) level, serum concentrations of homocysteine and cholesterol, plasma oxidized low density-lipoprotein (LDL), concentration and plasma glutathione peroxidase (GSH-Px) activity in the patients with type 2 diabetes. A total of 92 type 2 diabetes patients participated voluntarily with written consents. They were divided into one of the four experimental groups; Control (C), Folate-supplemented (F), Ascorbate-supplemented (A), and Folate plus ascorbate-supplemented (FA). The subjects in C were taken placebo, those in F were supplemented 1 mg of folate, those in A received 1,000 mg of ascorbate, and those in FA were given 1 mg of folate plus 1,000 mg of ascorbate daily for 4 weeks. Supplementation of folate or ascorbate resulted to increase serum folate level or plasma ascorbate concentration apparently, respectively. Folate supplementation not ascorbate seemed to decrease plasma concentrations of homocysteine and oxidized LDL and reduce plasma GSH-Px activity. There might not be synergic effect of the supplementation of folate plus ascorbate. The results indicate that oxidative stress in the patients with type 2 diabetes may lower mainly by folate supplementation.

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

• 한국방사선학회논문지
• /
• 제13권3호
• /
• pp.339-348
• /
• 2019

본 연구는 건강검진을 목적으로 내원하여 경동맥초음파를 실시한 113명을 대상으로 하였다. 경동맥의 내중막 두께는 심혈관 질환 및 뇌혈관 질환과 유의한 상관관계를 보이는 것으로 알려져 있다. 임상에서 선별 검사로 많이 이용되고 있는 경동맥 초음파를 이용하여 경동맥 내중막 두께와 체질량지수, 허리둘레, 혈청지질수치, 공복 혈당, 당화혈색소, 혈압등이 갖는 연관 관계에 대하여 알아보고자 하였다. 경동맥초음파상 IMT두께가 0.8 mm 이상을 비정상으로 간주하고 죽상경화증(atherosclerosis)의 유무를 평가하였으며, 혈청검사를 통하여 지질학적 수치 및 공복혈당수치, 당화혈색소를 분류하여 상관관계를 알아보았다. 그 결과 허리둘레(p=.022), 저밀도 콜레스테롤(p=.004), 공복혈당수치(p=.019), 당화혈색소 수치(p=.002)가 죽상경화증(atherosclerosis을 일으키는 예측인자로 분석되었다. ROC 곡선 분석에서 허리둘레에서 민감도 87.80%(95% CI : 73.8-95.9), 특이도 41.67%(95% CI : 30.2-53.9), 저밀도 콜레스테롤에서 민감도 78.05%(95% CI : 62.4-89.4), 특이도 50.00%(95% CI : 38.0-62.0 공복혈당에서 민감도 73.11%(95% CI : 57.1-85.8), 특이도 61.11 (95% CI : 48.9-72.4)), 당화혈색소에서 민감도 82.93%(67.9-91.8), 특이도 43.06%(31.4-55.3)를 나타내었다. 로지스틱 회귀분석에서 죽상경화증(atherosclerosis) 발생위험성은 허리둘레(WC)>76 cm에서 0.248배, 저밀도 콜레스테롤(LDL-C)${\geq}124mg/dL$에서 3.475배, 당화혈색소(HbA1C)>5.4%에서 0.618배로 나타났다. 향후 심뇌혈관질환의 효과적인 일차예방 역할을 위해 다수의 대상자를 대상으로 혈액검사수치를 고려하여 혈관의 추적관찰이 용이한 경동맥초음파를 통한 전향적연구가 필요할 것으로 사료 된다.

• 한국식품영양과학회지
• /
• 제36권11호
• /
• pp.1391-1398
• /
• 2007

본 연구는 다시마의 활성성분을 열수추출하고, 그 추출물을 제 2형 당뇨병 환자에게 섭취시킴으로서 그들의 혈당, 혈중지질 및 항산화 체계 개선에 있어서 다시마추출물의 효능을 과학적으로 규명하고자 하였다. 다시마를 열수추출하고 동결건조한 후 캡슐화하여 1.4 g을 350 mg씩 4캡슐로 나누어, 아침과 저녁 식후에 2캡슐씩 제 2형 당뇨환자에게 12주간 섭취 시켰다. 위약군은 동량의 cellulose를 실험군과 동일하게 제조한 후 같은 방법으로 섭취하게 하였고 이중맹검법을 사용하였다. 섭취 전후 일반사항 및 식이섭취조사, 신체계측을 실시하였고, 혈액을 채취하여 혈당, 당화혈색소, 혈청지질, 지질과산화물 및 항산화 효소의 변화와 독성검사인 간 및 신장 기능의 변화를 측정하였다. 최종 연구는 총 37명으로 실험군 17명, 대조군 20명으로 양군간의 baseline 특성은 유의적 차이가 없었다. 다시마추출물 섭취군에서 공복혈당은 12주간 섭취 후 $156.0{\pm}15.2mg/dL$에서 $155.8{\pm}14.2mg/dL$로 나타났고, 당화혈색소 역시 $6.74{\pm}0.66%$에서 $6.65{\pm}0.64%$으로 유의적으로 감소하지 않았다. 다시마추출물의 섭취가 12주간 이루어지면서 총콜레스테롤은 $177.0{\pm}16.5mg/dL$에서 $168.6{\pm}15.0mg/dL$로 유의적 (p<0.05)으로 감소한 반면에, 위약군의 경우 $175.8{\pm}17.4mg/dL$에서 $179.8{\pm}19.9$로 변화되었다. 또한 다시마추출물 섭취군의 LDL-콜레스테롤, 중성지방의 변화에서도 섭취 전에 비해 섭취 후 유의적 (p<0.05) 감소를 나타내었으며, 특히 LDL-콜레스테롤의 농도를 고농도군, 정상군, 저농도군으로 분류시 LDL-콜레스테롤 농도가 높은 환자일수록 감소의 폭이 큼을 알 수 있었다. 지질과산물 농도의 변화를 보면 다시마추출물 섭취군은 $1.58{\pm}0.88nmol$에서 $1.13{\pm}0.03nmol$로 유의적(p<0.05)으로 감소되었고, GSH-px활성도 위약군에 비해 다시마추출물 섭취군은 $13.98{\pm}0.66I.U/mg$ protein에서 $14.58{\pm}0.22I.U/mg$ protein로 활성도가 약간 상승하였다. SOD 활성은 실험군($1.18{\pm}0.22$ vs. $1.28{\pm}0.18unit/mg$ protein)에서 유의적(p<0.05)으로 증가하였으며, 간 및 신장 기능 검사에서도 실험 전후 모든 군이 정상범위를 나타내었다. 따라서 본 연구는 당뇨병 환자들의 혈청지질 및 혈액 항산화 효소계에 도움을 줄 수 있는 안전한 보조제로서 다시마추출물의 사용 가능성을 제시하였다.