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.
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 $Ca^{2+}$.
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.
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.
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.
Journal of the Korea Academia-Industrial cooperation Society
/
v.21
no.8
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pp.348-358
/
2020
The purpose of this study was to examine the effects of auricular acupressure in patients with type 2 diabetes mellitus. Data collection was conducted from March 16 to May 11, 2018. A total of 44 participants with type 2 diabetes were recruited from welfare facilities. Participants in the experimental group (n=22) and placebo control group (n=22) received auricular acupressure on diabetes-related points (shenmen, pancreas, appetite control point, thirst point, and master endocrine point) and diabetes-unrelated points. The intervention was implemented on 5 consecutive days per week for a total of 6 weeks. To examine the effects of treatment, postprandial glucose, glycated hemoglobin, and blood lipid levels were evaluated. Postprandial glucose levels in the experimental group exhibited significant reduction over time compared to those in the placebo control group (p=.030). Glycated hemoglobin levels in the experimental group decreased significantly (t=-2.44, p=.024). However, there were no significant differences in blood lipid levels between the two groups. This study demonstrates that auricular acupressure on diabetes-related points for 6 weeks was highly effective in decreasing blood glucose levels in patients with type 2 diabetes.
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.
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 purpose of this study was to investigate the effect of carotid artery ultrasound Respectively. The carotid intima-media thickness is known to have a significant correlation with cardiovascular disease and cerebrovascular disease. We investigated the relationship between carotid intima - media thickness, body mass index, waist circumference, the blood lipid value, fasting blood glucose, glycated hemoglobin, and blood pressure using carotid artery ultrasound. The carotid artery ultrasound was considered to be abnormality of IMT thickness over 0.8 mm and the presence or absence of atherosclerotic plaque was evaluated. Serological tests were used to compare the geologic value, fasting blood glucose level, and glycated hemoglobin. As a result, waist circumference (=.022), low density cholesterol (=.004), fasting blood glucose level (.019), and glycemic index (.002) were analyzed as predictors of atherosclerosis. In the ROC curve analysis, sensitivity was 87.80% (95% CI: 73.8-95.9), specificity was 41.67% (95% CI: 30.2-53.9), sensitivity was 78.05% (95% CI: 62.4-89.4) in low density lipoprotein, Specificity was 50.00% (95% CI: 38.0-62.0), sensitivity was 73.11% (95% CI: 57.1-85.8), specificity was 61.11 (95% CI: 48.9-72.4) and sensitivity was 82.93%-91.8) and a specificity of 43.06% (31.4-55.3). In logistic regression analysis, the risk of atherosclerosis was 0.248 times at waist circumference (WC)> 76 cm, 3.475 times at low-density lipoprotein (LDL-C) ${\geq}124mg/dL$, 0.618 at HbA1c> 5.4% It appeared as a times. We suggest that prospective study of carotid artery ultrasound should be performed for the effective prevention of cardiovascular diseases.
Journal of the Korean Society of Food Science and Nutrition
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v.36
no.11
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pp.1391-1398
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2007
We performed a randomized double-blind placebo-controlled trial to determine whether Laminaria japonica extract (LJE) supplement modulates blood glucose, serum lipids and antioxidant systems in type II diabetic patients. We also measured critical parameters assessing safety in liver and kidney functions after LJE supplement. A total of 37 patients (18 males and 19 females) were randomized to either LJE group or placebo group. The treatment group received four 350 mg of LJE capsules (1.4 g, total) per day for 12 weeks. The placebo group received the same dose of cellulose capsules. Baseline characteristics regarding general life style and dietary intake pattern were similar between the two groups. There were no significant influences of LJE supplement except for waist circumference on anthropometric parameters. As the whole, 12 weeks of LJE supplement resulted in a little decrease in fasting blood glucose (FBG) and glycated hemoglobin (HbA1c), but a significant decrease was not observed. Total cholesterol, LDL-cholesterol and triglyceride concentrations were significantly (p<0.05) lowered in LJE group. The antioxidant enzymes, glutathion peroxidase (GSH-px) and superoxide dismutase (SOD) levels were elevated in the LJE group (p<0.05) compared to the placebo. The increase of these enzymes was associated significantly with the decrease of MDA concentration (p<0.05). Furthermore, LJE supplement showed no adverse effects on the functions of liver and kidney. Findings from this study suggest that LJE supplement can help improve serum lipid status in type II diabetic subjects without adverse effects.
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