Saturated fatty acids contribute to β-cell dysfunction in the onset of type 2 diabetes mellitus. Cellular responses to lipotoxicity include oxidative stress, endoplasmic reticulum (ER) stress, and blockage of autophagy. Palmitate induces ER Ca2+ depletion followed by notable store-operated Ca2+ entry. Subsequent elevation of cytosolic Ca2+ can activate undesirable signaling pathways culminating in cell death. Mitochondrial Ca2+ uniporter (MCU) is the major route for Ca2+ uptake into the matrix and couples metabolism with insulin secretion. However, it has been unclear whether mitochondrial Ca2+ uptake plays a protective role or contributes to lipotoxicity. Here, we observed palmitate upregulated MCU protein expression in a mouse clonal β-cell, MIN6, under normal glucose, but not high glucose medium. Palmitate elevated baseline cytosolic Ca2+ concentration ([Ca2+]i) and reduced depolarization-triggered Ca2+ influx likely due to the inactivation of voltage-gated Ca2+ channels (VGCCs). Targeted reduction of MCU expression using RNA interference abolished mitochondrial superoxide production but exacerbated palmitate-induced [Ca2+]i overload. Consequently, MCU knockdown aggravated blockage of autophagic degradation. In contrast, co-treatment with verapamil, a VGCC inhibitor, prevented palmitate-induced basal [Ca2+]i elevation and defective [Ca2+]i transients. Extracellular Ca2+ chelation as well as VGCC inhibitors effectively rescued autophagy defects and cytotoxicity. These observations suggest enhanced mitochondrial Ca2+ uptake via MCU upregulation is a mechanism by which pancreatic β-cells are able to alleviate cytosolic Ca2+ overload and its detrimental consequences.
Xu, EnShi;Shin, Jinho;Lim, Ji Eun;Kim, Mi Kyung;Choi, Bo Youl;Shin, Min-Ho;Shin, Dong Hoon;Lee, Young-Hoon;Chun, Byung-Yeol;Hong, Kyung-Won;Hwang, Joo-Yeon
Journal of Genetic Medicine
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v.14
no.1
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pp.8-17
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2017
Purpose: Pulse wave velocity (PWV) is an indicator of arterial stiffness, and is considered a marker of vascular damage. However, a genome-wide association study analyzing single nucleotide polymorphisms (SNPs) associated with brachial-ankle PWV (baPWV) has not been conducted in healthy populations. We performed this study to identify SNPs associated with baPWV in healthy populations in Korea. Materials and Methods: Genomic SNPs data for 2,407 individuals from three sites were analyzed as part of the Korean Genomic Epidemiologic Study. Without replication samples, we performed multivariable analysis as a post hoc analysis to verify the findings in site adjusted analysis. Healthy subjects aged between 40 and 70 years without self-reported history or diagnosis of hypertension, diabetes, hyperlipidemia, heart disease, cerebrovascular disease and cancer were included. We excluded subjects with a creatinine level >1.4 mg/dL (men) and 1.2 mg/dL (women). Results: In the site-adjusted association analysis, significant associations (P<$5{\times}10^{-8}$) with baPWV were detected for only 5 SNPs with low minor allele frequency. In multivariable analysis adjusted by age, sex, height, body mass index, mean arterial pressure, site, smoking, alcohol, and exercise, 11 SNPs were found to be associated (P<$5{\times}10^{-8}$) with baPWV. The 5 SNPs (P<$5{\times}10^{-8}$) linked to three genes (OPCML, PRR35 and RAB40C) were common between site-adjusted analysis and multivariable analysis. However, meta-analysis of the result from three sites for the 11 SNPs showed no significant associations. Conclusion: Using the recent standard for genome-wide association study, we did not find any evidence of significant association signals with baPWV.
Mo, Eun Kyoung;Kim, Seung Mi;JeGal, Sung A;Choi, Young Sim;Song, Chil Suk;An, Sang Lan;Lee, Myung Ho;Sung, Chang Keun
Korean Journal of Food Science and Technology
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v.45
no.1
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pp.40-46
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2013
The present study was performed to increase the availability of sweet (Ipomoea batatas) and to develop dinner roll with the reducing ability of blood glucose levels. Different contents of lyophilized sweet potato powder (SPP) were added in dinner roll. Compare to the control group, batter density, a value, hardness, and cohesiveness of the SPP-treated groups were significantly increased while dough expansion rate, baking loss rate, L value, and Hue angle were significantly decreased. Twenty four Sprague-Dawley rats were administered with the SPP-treated diet for 4 weeks after diabetes was induced with the injection of streptozotocin. The blood glucose concentration of the SPP-treated group was significantly lower than that of the control. Although the SPP-treated groups possessed the ability of reducing blood glucose level, the sensory qualities were inferior to the control. Thus, follow-up study was required to improve the sensory characteristics as well as the texture properties.
Kim, Na-Eun;Lee, Mi-Ok;Jang, Mi-Hee;Chung, Byung-Hee
Korean Journal of Food Science and Technology
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v.50
no.3
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pp.349-355
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2018
Ginsenoside Rg5, one of the protopanaxadiol ginsenosides of wood-cultivated ginseng, has been implicated in various diseases, such as diabetes, cancer, and hypertension; however, its angiogenic activity and molecular mechanisms have not yet been elucidated. Here, we found that wood-cultivated ginseng extract and ginsenoside Rg5 increase in vitro proliferation, migration, and tube-like structure formation, which are typical phenomena associated with angiogenesis, in cultured human umbilical vein endothelial cells (HUVECs). Moreover, Ginsenoside Rg5 stimulated the phosphorylation of Akt, endothelial nitric oxide (NO) synthase (eNOS), and extracellular-regulated kinase (ERK)1/2, which are well-known signal mediators of the angiogenic pathway. Furthermore, Ginsenoside Rg5 did not accelerate the activation of ICAM-1 and VCAM-1 which are inflammatory response mediators. These results suggest that wood-cultivated ginseng extract and ginsenoside Rg5 stimulated in vitro angiogenesis by activating the Akt/eNOS- and ERK1/2-dependent signal pathways without inducing vascular inflammation.
Obesity and diabetes mellitus are associated with common pathogenic mechanism, and ${\beta}-glucan$ of Agaricus blazei Murill is potent inhibitor of intestinal ${\alpha}-glycosidase$ and inhibit the digestion of starch and sucrose in the small intestine. In this studies, there was observed the anti-hyperglycemic effect in obese diabetic mice(C57BLKsJ db/db), which were supplied Agaricus and Acarbose for 5 weeks. In db/db mice, food intake and body weight gain were decreased significantly in Agaricus groups(p<0.05). Also these group exhibited lower fasting serum glucose level compared with control group. HbA1c level, triglyceride level, total cholesterol level, HDL cholesterol level, LDL cholesterol level and VLDL cholesterol level were lowered in db/db mice. The activity of disaccharidases on proximal and distal segments of small intestine was decreased. In conclusion, it was assumed that ${\beta}-glucan$ of Agaricus blazei Murill has anti-hyperglycemic and anti-obesitic effects by reducing food intake and body weight gain, and also decreasing serum glucose and lipid level through inhibiting the activity of small intestinal disaccharidases.
Background : Nervous system dysfunction is a major complication of end stage renal disease. Although severe neurologic symptoms are partially or completely reversed by adequate hemodialysis, even optimally dialyzed patients will usually not return to normal neurocognitive function. To investigate the influence of chronic renal failure and hemodialysis on higher cognitive function electrophysiologically, we studied auditory P300 event-related potentials in 14 hemodialysis patients and 14 age- and sex-matched normal healthy controls. Methods : The subjects consisted of 14 patients(M: 6, F: 8) with chronic renal failure(CRF) for 1 to 10 years and 14 age- and sex-matched healthy controls(M: 5, F: 9). For the reliability of study, patients with diabetes mellitus, abnormal brain CT findings, or low mini-mental state score(below 20) were excluded. Event related potentials(ERPs) for hemodialysis patients were performed at pre- and post-hemodialysis. To obtain ERPs, subjects underwent 2-tone auditory discrimination test(oddball paradigm). Results : Although the age(control: $48.79{\pm}10.31years$, CRF: $51.21{\pm}7.61years$) and mini-mental state score(control: $27.00{\pm}1.71points$, predialysis CRF: $25.07{\pm}3.58points$) were not different in normal control and CRF groups significantly(P>0.05), P300 latencies at Cz(control: $288.11{\pm}17.36msec$, predialysis CRF: $332.35{\pm}42.34msec$) were significantly delayed(P<0.05)and the duration of Trail making test A was significantly prolonged(control: $64.2{\pm}24.2sec$, CRF: $118.9{\pm}101sec$) in CRF group. P300 latencies between pre- and post-hemodialysis CRF patients(predialysis CRF: $332.35{\pm}42.34msec$, postdialysis CRF: $325.82{\pm}38.69msec$) were not significantly different. The P300 latency was not related with the duration of CRF(Spearman's correlation test, r=0.25, P>0.05) and the frequency of hemodialysis(Spearman's correlation test, r=0.28, P>0.05). Conclusions : From these results, we suggest that P300 latency is valuable in evaluating cognitive brain dysfunction in patients with CRF and hemodialysis does not have a significant effect on cognitive brain dysfunction in patients with CRF.
Park, Kyung-Soon;Song, Yeon-Yi;Park, Mi-Sook;Kim, Kyoung-Oak;Choi, Seong-Su;Kim, Kyung-Ah;Ryu, Jae-Duck;Cha, Eun-Jong
Journal of the Korea Academia-Industrial cooperation Society
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v.10
no.9
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pp.2451-2459
/
2009
The present study aimed to evaluate the accuracy of the blood glucose test with almost painless vacuum assisted auto-lancing technique. The blood glucose concentration measurements in the capillary blood sampled from the alternative (forearm) site were compared with the standard venous or finger sampling techniques. Capillary blood was sampled from both the left index finger and the forearm, followed by the venous blood sampling in 531 patients who visited the C University Hospital. Blood sugar test was performed for each blood samples for comparative analysis. Mean blood glucose concentration measured on the forearm was closer to the venous glucose level than that of the finger, but the difference was approximately 10 mg/dL small enough to ignore from the clinical point of view. The correlation coefficients of the measured blood glucose levels between finger and vein and between forearm and vein were 0.94 and 0.92, respectively (p<0.001). The blood glucose measurement on the forearm also well correlated with the finger, showing a correlation coefficient of 0.94, and both data were very much close to each other. Therefore, the blood sugar test on the alternative capillary blood sampling site such as forearm was accurate enough for clinical practice. The vacuum assisted auto-lancing technique on the alternative site would be of particular interest for the disease management of the chronic diabetes, since it induces almost no pain when sampling blood from the capillaries.
Journal of the Korea Academia-Industrial cooperation Society
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v.17
no.9
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pp.141-155
/
2016
This research is a descriptive study that aimed to identify the health knowledge and optimistic bias related to stroke of middle-aged adults and the effect these had on their health-promoting lifestyle. The research was conducted from July 15 to August 15, 2015. The research subjects were 191 adults aged between 40 to 60 years. A structured questionnaire was used and self-administered for data collection. The PASW Statistics 21.0 and AMOS 21.0 programs were used for data analysis, and analysis of variance, correlation analysis, and structural equation modeling analysis were conducted. It was found that the middle-aged adults recognized smoking and hypertension as higher risk factors for stroke than diabetes, and there was a slight optimistic bias for stroke. Health knowledge about stroke had correlations with optimistic bias (r = -.143, p = .048) and health-promoting lifestyle (r = .268, p = < .001), while optimistic bias had correlations with interpersonal relationships and stress (r = .177, p = .014) in health-promoting lifestyle. In addition, health-promoting lifestyle affected health knowledge more than optimistic bias. In conclusion, it was found that the active information acquisition, health knowledge, and optimistic bias of middle-aged adults toward stroke were important factors pertaining to a stroke-related health-promoting lifestyle. Therefore, an education program to improve the health-promoting lifestyle related to stroke in middle-aged adults should be considered as a way to enhance stroke-related health knowledge and reduce optimistic bias.
Recently it has been reported that vitamin A and retinol binding proteins (RBPs) in blood and urine were changed in the condition of diabetes mellitus or hyperlipidemia. Fruits and vegetables are recommended to consume for the people suffered from these chronic degenerative diseases. The main components of fruits and vegetables are dietary fibers, for example cellulose and pectin, of which function to affect the absorption and excretion of dietary fat and fat-soluble substances. This study was conducted to investigate the effect of dietary fibers on RBPs mRNA expression in liver, small intestine and serum of rat fed high fat diet during 4 weeks. Sprague-Dawley rats, weighing 121g on average, were divided into four groups; (Control; $17\%$ fat & cellulose supplement diet, HF0: $25\%$ fat & fiber free diet, B:.Uc: $25\%$ fat & cellulose supplement diet and HF0: $25\%$ fat & pectin supplement diet) . The rats fed high fat diet groups (HF0, HFC, HFP) tended to consume the food less than the control group, but FER of HF0 groups was significantly higher than the control (p < 0.05) . The weight of adrenal gland in high fat diet groups (HF0, HFC, HFP) was significantly less than the control. Total lipid in feces daily excreted and in liver did not show any significant differences among the groups. Total cholesterol in HFP group was significantly different from that of HFC group. Serum total cholesterol and triglyceride in other group tended to lower than other groups and HDL cholesterol higher. Consequently, AI (atherogenic index) was the lowest in HFP group. Vit A contents in feces daily excreted tended to lower in high fat diet groups (HF0, HFP) compared to the control group. That content in adrenal gland was the lowest in HF0 group, but not in liver. In HFP group were down-regulated cRBPI mRNA in liver and cRBPII mRNA in small intestine and up-regulated RBP and transthyretin expression in serum compared to the other groups. In conclusion, dietary fibers, especially pectin, in high fat diet might down-regulate the expression of CRBP I, CRBP II mRNA in liver and small intestine, but increase the secretion of RBP into serum and therefore inhance the bioavailability of Vit A through the body. (Korean J Nutrition 38(10): 817$\sim$826,2005)
This study was designed to examine the effects of fractions of ethanol extract of Benincasa hispida (wax gourd) on plasma glucose and lipid levels in streptozotocin (STZ) induced diabolic rats. sprague-Dawley rats were induced diabetes mellitus by STZ injection (45 mg/kg) into the tail vein and were divided into 5 groups: normal, STZ-control, three experimental diabetic groups. fractions of ethanol extract of Benincasa hispida were administered orally into the diabetic rats for 14 days. The food intake and body weight were monitored and plasma levels of glucose, cholesterol, HDL-cholesterol, triglyceride (TG) , free fatty acid (FFA) , and aminotransferase activity were analyzed. A significant lowering effects of plasma glucose levels were observed in the chloroform fraction and $H_2O$ fraction group compared to STZ-control group at 14 days. Administrations of each of the three fractions decreased plasma TG and FFA levels in diabetic rats. Activity of alanine aminotransferase (ALT) in $CHCl_3$ fraction and $H_2O$ fraction groups and aspartate aminotransferase (AST) in $H_2O$ fraction group significantly lower than STZ-control group. The results show that $CHCl_3$ fraction of Benincasa hispida could be effective to control the STZ-induced diabetic rats. (Korean J Nutrition 38(10): 801$\sim$806,2005)
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