- High Glucose and/or Free Fatty Acid Damage Vascular Endothelial Cells via Stimulating of NAD(P)H Oxidase-induced Superoxide Production from Neutrophils.
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Sang Soo Kim, Sun Young Kim, Soo Hyung Lee, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son
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Korean Diabetes J. 2009;33(2):94-104. Published online April 1, 2009
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DOI: https://doi.org/10.4093/kdj.2009.33.2.94
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- BACKGROUND
Oxidative stress and inflammation are important factors in the pathogenesis of diabetes and contribute to the development of diabetic complications. To understand the mechanisms that cause vascular complications in diabetes, we examined the effects of high glucose and/or free fatty acids on the production of superoxide from neutrophils and their role in endothelial cell damage. METHODS: Human neutrophils were incubated in the media containing 5.5 mM D-glucose, 30 mM D-glucose, 3 nM oleic acid, or 30 microM oleic acid for 1 hour to evaluate superoxide production through NAD(P)H oxidase activation. Human aortic endothelial cells were co-cultured with neutrophils exposed to high glucose and oleic acid. We then measured neutrophil adhesion to endothelial cells, neutrophil activation and superoxide production, neutrophil-mediated endothelial cell cytotoxicity and subunits of neutrophil NAD(P)H oxidase. RESULTS: After 1 hour of incubation with various concentrations of glucose and oleic acid, neutrophil adherence to high glucose and oleic acid-treated endothelial cells was significantly increased compared with adhesion to low glucose and oleic acid-treated endothelial cells. Incubation of neutrophils with glucose and free fatty acids increased superoxide production in a dose-dependent manner. High glucose and oleic acid treatment significantly increased expression of the membrane components of NAD(P)H oxidase of neutrophil (gp91(phox)). Endothelial cells co-cultured with neutrophils exposed to high glucose and oleic acid showed increased cytolysis, which could be prevented by an antioxidant, N-acetylcysteine. CONCLUSION: These results suggest that high glucose and/orfree fatty acidsincrease injury of endothelial cells via stimulating NAD(P)H oxidase-induced superoxide production from neutrophils.
- Cause-of-Death Trends for Diabetes Mellitus over 10 Years.
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Su Kyung Park, Mi Kyoung Park, Ji Hye Suk, Mi Kyung Kim, Yong Ki Kim, In Ju Kim, Yang Ho Kang, Kwang Jae Lee, Hyun Seung Lee, Chang Won Lee, Bo Hyun Kim, Kyung Il Lee, Mi Kyoung Kim, Duk Kyu Kim
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Korean Diabetes J. 2009;33(1):65-72. Published online February 1, 2009
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DOI: https://doi.org/10.4093/kdj.2009.33.1.65
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Abstract
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- BACKGROUND
Recently, diabetic mortality is lower than ever before, likely due to dramatic improvements in diabetes care. This study set to analyze changes in the cause of death in type 2 diabetes mellitus (T2DM) in the past 10 years. METHODS: All subjects were T2DM patients over the age of 30 whose death certificates were issued at six hospitals in the Busan metropolitan area from 2000 to 2004. The patients were excluded if they had been clinically diagnosed with significant tuberculosis, liver, thyroid, renal, connective tissue diseases and cancers, prior to T2DM diagnosis. We classified the cause of death into several groups by KCD-4. The results were compared with published data on the period from 1990 to 1994. RESULTS: The study comprised 680 patients, of which 374 (55.0%) were male. The average age of death was 66.3 +/- 10.7 years. The most common cause of death was cardiovascular disease (30.6%), followed by infectious disease (25.3%), cancer (21.9%), congestive heart failure (7.1%), renal disease (4.7%), liver disease (2.7%), and T2DM itself (1.9%). In the study from the earlier period, the most common cause of death was also cardiovascular disease (37.6%), followed by infectious disease (24.2%), T2DM (6.0%), liver disease (5.4%), cancer (4.7%), and renal disease (3.3%). CONCLUSION: Over both study periods, the first and second cause of death in T2DM were cardiovascular disease and infectious disease, respectively. However, death by cerebral infarction among cardiovascular disease patients was significantly lower in the latter period, while death by malignancy was markedly increased.
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Heesun Kim, Eun-Jung Kim Healthcare.2022; 10(9): 1601. CrossRef - Arterial stiffness is an independent predictor for risk of mortality in patients with type 2 diabetes mellitus: the REBOUND study
Jeong Mi Kim, Sang Soo Kim, In Joo Kim, Jong Ho Kim, Bo Hyun Kim, Mi Kyung Kim, Soon Hee Lee, Chang Won Lee, Min Chul Kim, Jun Hyeob Ahn, Jinmi Kim Cardiovascular Diabetology.2020;[Epub] CrossRef - The Mentors, The Social Support and Patients with Diabetes Mellitus
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Jae-Cheol Park, Jea-Young Lee Journal of Applied Statistics.2018; 45(16): 2999. CrossRef - Impact of change in job status on mortality for newly onset type II diabetes patients: 7 years follow-up using cohort data of National Health Insurance, Korea
Donggyo Shin, Ji Man Kim, Tinyami Erick Tandi, Eun-Cheol Park Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2016; 10(1): S1. CrossRef - Factors Associated with Poor Glycemic Control among Patients with Type 2 Diabetes Mellitus: The Fifth Korea National Health and Nutrition Examination Survey (2010-2012)
Jinhyun Park, Seungji Lim, Eunshil Yim, Youngdae Kim, Woojin Chung Health Policy and Management.2016; 26(2): 125. CrossRef - Mortality and causes of death in a national sample of type 2 diabetic patients in Korea from 2002 to 2013
Yu Mi Kang, Ye-Jee Kim, Joong-Yeol Park, Woo Je Lee, Chang Hee Jung Cardiovascular Diabetology.2016;[Epub] CrossRef - Development of Cell Phone Application for Blood Glucose Self-Monitoring Based on ISO/IEEE 11073 and HL7 CCD
Hyun Sang Park, Hune Cho, Hwa Sun Kim Healthcare Informatics Research.2015; 21(2): 83. CrossRef - Cost-Utility Analysis of Screening Strategies for Diabetic Retinopathy in Korea
Sang-Won Kim, Gil-Won Kang Journal of Korean Medical Science.2015; 30(12): 1723. CrossRef - Quality characteristics of brown rice boiled with medicinal herbs extract for diabetes prevention
Kyung-Mi Yang, Jung-Ran Park, Su-Jung Hwang Korean Journal of Food Preservation.2014; 21(1): 55. CrossRef - Does Diabetes Mellitus Influence Standardized Uptake Values of Fluorodeoxyglucose Positron Emission Tomography in Colorectal Cancer?
Da Yeon Oh, Ji Won Kim, Seong-Joon Koh, Mingoo Kim, Ji Hoon Park, Su Yeon Cho, Byeong Gwan Kim, Kook Lae Lee, Jong Pil Im Intestinal Research.2014; 12(2): 146. CrossRef - The Relationship between Metformin and Cancer in Patients with Type 2 Diabetes
Hyun Hee Chung, Jun Sung Moon, Ji Sung Yoon, Hyoung Woo Lee, Kyu Chang Won Diabetes & Metabolism Journal.2013; 37(2): 125. CrossRef - Relationship between Milk and Calcium Intake and Lipid Metabolism in Female Patients with Type 2 Diabetes
JaeHee Kim, Ji-Yun Hwang, Ki Nam Kim, Young-Ju Choi, Namsoo Chang, Kap-Bum Huh Yonsei Medical Journal.2013; 54(3): 626. CrossRef - Comorbidity Study on Type 2 Diabetes Mellitus Using Data Mining
Hye Soon Kim, A Mi Shin, Mi Kyung Kim, Yoon Nyun Kim The Korean Journal of Internal Medicine.2012; 27(2): 197. CrossRef - Glucose, Blood Pressure, and Lipid Control in Korean Adults with Diagnosed Diabetes
Sun-Joo Boo Korean Journal of Adult Nursing.2012; 24(4): 406. CrossRef - A Comparative Study of Eating Habits and Food Intake in Women with Gestational Diabetes according to Early Postpartum Glucose Tolerance Status
You Jeong Hwang, Bo Kyung Park, Sunmin Park, Sung-Hoon Kim Diabetes & Metabolism Journal.2011; 35(4): 354. CrossRef - Diabetes and Cancer: Is Diabetes Causally Related to Cancer?
Sunghwan Suh, Kwang-Won Kim Diabetes & Metabolism Journal.2011; 35(3): 193. CrossRef - The Association between Type 2 Diabetes Mellitus and Colorectal Cancer
Byeong Do Yi, Young Pil Bae, Bong Gun Kim, Jong Wha Park, Dong Hyun Kim, Ja Young Park, Seong Ho Choi, Hee Seung Park, Jae Seung Lee, Chang Won Lee, Sang Soo Kim, Bo Hyun Kim, Moon Ki Choi, In Joo Kim Endocrinology and Metabolism.2011; 26(2): 126. CrossRef - The Hypoglycemic Effect of Complex of Chinese Traditional Herbs (CTH) and Macelignan in Type 2 Diabetic Animal Model
Journal of Life Science.2010; 20(7): 1113. CrossRef - The Relationship Between Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes
Hyun Ae Seo, Yeon Kyung Choi, Jae Han Jeon, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, In Kyu Lee, Bo Wan Kim, Jung Guk Kim Korean Diabetes Journal.2009; 33(6): 485. CrossRef - Epidemiologic Characteristics of Diabetes Mellitus in Korea: Current Status of Diabetic Patients Using Korean Health Insurance Database
Ie Byung Park, Sei Hyun Baik Korean Diabetes Journal.2009; 33(5): 357. CrossRef - Cause-of-Death Trends for Diabetes Mellitus over 10 Years (Korean Diabetes J 33(1):65-72, 2009)
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- Association of Serum Cystatin C with Metabolic Syndrome and Its Related Components in Korean Adults.
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Sun Young Kim, Sang Heon Song, Yun Kyung Jeon, Ji Ryang Kim, Jung Ho Bae, Sang Soo Kim, Soo Hyung Lee, Seok Man Son, In Ju Kim, Yong Ki Kim, Yang Ho Kang
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Korean Diabetes J. 2008;32(5):409-417. Published online October 1, 2008
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DOI: https://doi.org/10.4093/kdj.2008.32.5.409
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2,655
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Abstract
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- BACKGROUND
Serum cystatin C has been reported as a better marker than serum creatinine for estimation of kidney function and may be associated with cardiovascular disease. The aim of this study was to elucidate the association of serum cystatin C with metabolic syndrome (MS), a constellation of cardiovascular risk factors, and its related components and the usefulness of serum cystatin C for the cardiovascular risk assessment. METHODS: 1,468 healthy subjects (814 men and 655 women), who visited health promotion center of Pusan National University Hospital for routine medical checkup were included. MS was defined by modified, revised National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria. RESULTS: Mean serum cystatin C value was 0.87 +/- 0.17 mg/L. In partial correlation analysis adjusted by age, sex and Glomerular Filtration Rate (GFR), cystatin C was associated with most of metabolic parameters and especially had significant positive correlation with waist circumference (r = 0.215), triglyceride (TG) (r = 0.141), diastolic blood pressure (BP) (r = 0.116), and correlated negatively with high density lipoprotein (HDL) cholesterol (r = -0.152) (all P < 0.001). There were increasing trends of prevalence of MS with the increase of quartiles of cystatin C and as the number of MS components increased, cystatin C values significantly increased. Serum cystatin C was also significantly increased in MS (0.90 +/- 0.19 mg/L vs. 0.86 +/- 0.16 mg/L). In stepwise multiple regression analysis including the components of MS, Waist circumference, diastolic BP, triglyceride, and HDL cholesterol were independent determinants of serum cystatin C, but with creatinine, only waist circumference was independent determinant. CONCLUSIONS: Serum cystatin C was closely associated with MS and its related cardiovascular risk factors and might be useful as a tool of cardiovascular risk assessment.
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Citations
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- Cystatin C in Patients of Metabolic Syndrome and its Correlation with the Individual Components of Metabolic Syndrome
Sunita Aghade, Jayshree S Bavikar, Pragati S Kadam, Reshakiran J Shendye Indian Journal of Medical Biochemistry.2019; 23(2): 293. CrossRef - Cystatin C as a Predictor for Diabetes according to Glycosylated Hemoglobin Levels in Korean Patients
Eon Ju Jeon, Ji Hyun Lee Diabetes & Metabolism Journal.2016; 40(1): 32. CrossRef - Association of Obesity with Serum Cystatin C in Korean Adults
Yang Ho Kang The Korean Journal of Obesity.2015; 24(4): 199. CrossRef
- Migration of Vascular Smooth Muscle Cells by High Glucose is Reactive Oxygen Dependent.
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Yong Seong An, Ji Hae Kwon, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son
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Korean Diabetes J. 2008;32(3):185-195. Published online June 1, 2008
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DOI: https://doi.org/10.4093/kdj.2008.32.3.185
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Abstract
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- BACKGROUND
Oxidative stress contributes to vascular diseases in patients with diabetes. As the mechanism of development and progression of diabetic vascular complications is poorly understood, this study was aimed to assess the potential role of hyperglycemia-induced oxidative stress and to determine whether the oxidative stress is a major factor in hyperglycemia-induced migration of vascular smooth muscle cells (VSMCs). METHODS: We treated primary cultured rat aortic smooth muscle cells for 72 hours with medium containing 5.5 mM D-glucose (normal glucose), 30 mM D-glucose (high glucose) or 5.5 mM D-glucose plus 24.5 mM mannitol (osmotic control). We measured the migration of VSMCs and superoxide production. Immunoblotting of PKC isozymes using phoshospecific antibodies was performed, and PKC activity was also measured. RESULTS: Migration of VSMCs incubated under high glucose condition were markedly increased compared to normal glucose condition. Treatment with diphenyleneiodonium (DPI, 10 micromol/L) and superoxide dismutase (SOD, 500 U/mL) significantly suppressed high glucose-induced migration of VSMCs. Superoxide production was significantly increased in high glucose condition and was markedly decreased after treatment with DPI and SOD. High glucose also markedly increased activity of PKC-delta isozyme. When VSMCs were treated with rottlerin or transfected with PKC-delta siRNA, nitro blue tetrazolium (NBT) staining and NAD(P)H oxidase activity were significantly attenuated in the high glucose-treated VSMCs. Furthermore, inhibition of PKC-delta markedly decreased VSMC migration by high glucose. CONCLUSION: These results suggest that high glucose-induced VSMC migration is dependent upon activation of PKC-delta, which may responsible for elevated intracellular ROS production in VSMCs, and this is mediated by NAD(P)H oxidase.
- The Association between Arterial Stiffness and Albuminuria in Type 2 Diabetes.
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Seong Geun Lee, Yong Ki Kim, Seo Rin Kim, Yong Sung Ahn, Ji Hae Kwon, Yang Ho Kang, Suk Man Son, In Joo Kim, Ju Sung Kim
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Korean Diabetes J. 2007;31(5):421-428. Published online September 1, 2007
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DOI: https://doi.org/10.4093/jkda.2007.31.5.421
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Abstract
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- BACKGROUND
Brachial ankle pulse wave velocity (BaPWV) and cardio ankle vascular index (CAVI), as indicators of arterial stiffness, are increased in type 2 diabetes. Albuminuria, as a cardiovascular risk factor in type 2 diabetes, can cause endothelial dysfunction and atherosclerosis, and these can increase arterial stiffness. So we investigated the hypothesis that increased albuminuria reflects increased BaPWV and CAVI in type 2 diabetes. METHODS: We retrospectively analyzed 106 patients (58 men and 48 women) with type 2 diabetes from March 2005 to September 2006. Urine albumin creatinine ratio (ACR) to evaluate urinary albumin excretion, BaPWV and CAVI were measured in all patients. RESULTS: All patients were divided 3 groups, normal group (ACR < 30 mg/g Cr., n = 31), microalbuminuria group(30 < or = ACR < or = 30 mg/g Cr., n = 42), proteinuria group(ACR > 300 mg/g Cr., n = 33). BaPWV and CAVI in microalbuminuria group and proteinuria group are faster than normal group. In bivariate correlation analysis, BaPWV was not associated with ACR, but CAVI was positively correlated to ACR (r = 0.285, P = 0.003). BaPWV was positively correlated to age, diabetes duration, body mass index, systolic blood pressure, diastolic pressure, pulse pressure and negatively correlated to glomerular filtration rate (GFR). CAVI was positively correlated to age, diabetes duration and negatively correlated to GFR. In multiple linear stepwise regression analysis, BaPWV was not associated with ACR, but ACR was independent predictor for CAVI (P = 0.002). CONCLUSION: In type 2 diabetes, albuminuria was independent predictor for indicators of arterial stiffness, especially CAVI.
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Citations
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- Associations Between Cardio-Ankle Vascular Index and Microvascular Complications in Type 2 Diabetes Mellitus Patients
Kwang Joon Kim, Byung-Wan Lee, Hyun-min Kim, Joo Youn Shin, Eun Seok Kang, Bong Soo Cha, Eun Jig Lee, Sung-Kil Lim, Hyun Chul Lee Journal of Atherosclerosis and Thrombosis.2011; 18(4): 328. CrossRef
- Oxidative Stress Causes Vascular Insulin Resistance in OLETF Rat Through Increased IRS-1 Degradation.
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Jung Lae Park, Young Sil Lee, Bo Hyun Kim, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son
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Korean Diabetes J. 2007;31(1):22-32. Published online January 1, 2007
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DOI: https://doi.org/10.4093/jkda.2007.31.1.22
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Abstract
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- BACKGROUND
Insulin resistance and oxidative stress have been reported to play essential pathophysiological roles in diabetic cardiovascular complication. The relationship between insulin resistance and oxidative stress in vasculature remains unclear. The study was conducted to assess whether oxidative stress induce vascular insulin resistance in OLETF rat, a model of type 2 diabetes METHODS: We used OLETF rats (20/30/40 weeks, n = 5/5/5), as models of type 2 DM, and LETO rats (20/30/40 weeks, n = 5/5/5) as controls. Aortas of each rats were extracted. Superoxide anion production was detected by NBT assay and lucigenin assay. 8-hydroxyguanosine (OHdG) and nitrotyrosine were detected as markers of oxidative stress in 20 and 40 weeks groups. The glucose uptake of aortas was measured by detecting 2-deoxyglucose uptake in both groups. The expression of IR, IRS-1, PI3-K and Akt/PKB were detected by immuno precipitation and immunoblotting in 20, 30 and 40 weeks groups RESULTS: Superoxide anion production and markers of oxidative stress (8-OHdG, nitrotyrosine) were significantly increased in aortas of OLETF rats compared with controls. Aortas of OLETF rats exhibited decreased IRS-1 content and increased phosphorylation of IRS-1 at Ser307 compared with LETO rats. There were no significant differences in expressions of IR, PI3-K and Akt/PKB between two groups CONCLUSION: These results suggest that oxidative stress induces insulin resistance in vasculature of OLETF rat specifically through increasing serine phosphorylation of IRS-1 and its degradation by a proteasome-dependent pathway, providing an alternative mechanism that may explain the association with insulin resistance and diabetic vascular complications.
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Citations
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- Anti-diabetic effects of benfotiamine on an animal model of type 2 diabetes mellitus
Kang Min Chung, Wonyoung Kang, Dong Geon Kim, Hyun Ju Hong, Youngjae Lee, Chang-Hoon Han Korean Journal of Veterinary Research.2014; 54(1): 21. CrossRef
- High Glucose Modulates Vascular Smooth Muscle Cell Proliferation Through Activation of PKC-sigma-dependent NAD(P)H oxidase.
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Bo Hyun Kim, Chang Won Lee, Jung Lae Park, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son
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Korean Diabetes J. 2006;30(6):416-427. Published online November 1, 2006
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DOI: https://doi.org/10.4093/jkda.2006.30.6.416
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Abstract
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- BACKGROUND
Oxidative stress is thought to be one of the causative factors contributing to macrovascular complications in diabetes. However, the mechanisms of development and progression of diabetic vascular complications are poorly understood. We hypothesized that PKC-sigma isozyme contributes to ROS generation and determined their roles in the critical intermediary signaling events in high glucose-induced proliferation of vascular smooth muscle (VSM) cells. METHODS: We treated primary cultured rat aortic smooth muscle cells for 72 hours with medium containing 5.5 mmol/L D-glucose (normal glucose), 30 mmol/L D-glucose (high glucose) or 5.5 mmol/L D-glucose plus 24.5 mmol/L mannitol (osmotic control). We then measured cell number, BrdU incorporation, cell cycle and superoxide production in VSM cells. Immunoblotting of PKC isozymes using phoshospecific antibodies was performed, and PKC activity was also measured. RESULTS: High glucose increased VSM cell number and BrdU incorporation and displayed significantly greater percentages of S and G2/M phases than compared to 5.5 mmol/L glucose and osmotic control. The nitroblue tetrazolium (NBT) staining in high glucose-treated VSM cell was more prominent compared with normal glucose-treated VSM cell, which was significantly inhibited by DPI (10 micrometer), but not by inhibitors for other oxidases. High glucose also markedly increased activity of PKC-sigma isozyme. When VSM cells were treated with rottlerin, a specific inhibitor of PKC-sigma or transfected with PKC-sigma siRNA, NBT staining and NAD(P)H oxidase activity were significantly attenuated in the high glucose-treated VSM cells. Furthermore, inhibition of PKC-sigma markedly decreased VSM cell number by high glucose. CONCLUSION: These results suggest that high glucose-induced VSM cell proliferation is dependent upon activation of PKC-sigma, which may responsible for elevated intracellular ROS production in VSM cells, and this is mediated by NAD(P)H oxidase.
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Citations
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- High Glucose and/or Free Fatty Acid Damage Vascular Endothelial Cells via Stimulating of NAD(P)H Oxidase-induced Superoxide Production from Neutrophils
Sang Soo Kim, Sun Young Kim, Soo Hyung Lee, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son Korean Diabetes Journal.2009; 33(2): 94. CrossRef
- Cell Cycle Progression of Vascular Smooth Muscle cell Through Modulation of p38 MAPK and GSK-3beta Activities Under High Glucose Condition.
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Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son
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Korean Diabetes J. 2005;29(5):418-431. Published online September 1, 2005
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- BACKGOUND: Macroangiopathy, with atherosclerosis, is the leading cause of mortality and morbidity in diabetic patients. Vascular smooth muscle cells play a crucial role in atherosclerosis, as they proliferate, migrate and express genes that encode inducible growth factors. However, the mechanisms induced by hyperglycemia that accelerate the proliferative change of vascular smooth muscle cells in diabetes remain unclear. This study was aimed at clarifying the respective roles of hyperglycemia in the acceleration of vascular complications in diabetes, examine the effects of hyperglycemia on vascular smooth muscle cell proliferation and the possible underlying mechanisms, including cell cycle progression. METHODS: Primary cultured rat aortic RASMs were exposed to normal glucose(5 mmol/L D-glucose), high glucose(30 mmol/L D-glucose) or an osmotic control (5mmol/L D-glucose plus 24.5 mmol/L mannitol) for 72 hours. The effect of high glucose on cell proliferation was determined by assessing the cell count and BrdU incorporation. Proteins involved in the cell proliferation pathway (PDK1, Akt/PKB, p42/44 MAPK, p38 MAPK, GSK-3beta) and those in cell cycle progression (cdk4, cyclin D, cdk2, cyclin E and ppRb phosphorylation) were determined by Western blot analysis. cdk4 kinase and PKC activity assays were also performed. RESULTS: A high level of glucose increased both the cell count(P<0.01) and BrdU incorporation(P<0.01). The PDK1, Akt/PKB and p42/44 MAPK activities were not significantly increased. A high level of glucose significantly increased the activities of p38 MAPK (P<0.01) and GSK-3beta(P<0.05) and the expressions of cdk4, cyclin D and ppRb phosphorylation. The cdk4 (P<0.01) and PKC (P<0.05) activities were also significantly increased. The inhibition of protein kinase C with GF109203X markedly reduced the phosphorylations of p38 MAPK and GSK-3betaand the expressions of cdk4 and cyclin D. In addition, pretreatment with GF109203X decreased the cell number in response to a high glucose level. CONCLUSION: These findings suggest that a high level of glucose increases vascular smooth muscle cell proliferation, with the possible mechanism further increases the G1 to S phase cell cycle progression via the activation of PKC, p38 MAPK and GSK-3beta.
- The Effect of High Glucose on the Proliferation and Migration of Vascular Smooth Muscle Cells.
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Mi Kyoung Kim, Yang Ho Kang, Seok Man Son, In Ju Kim, Yong Ki Kim
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Korean Diabetes J. 2004;28(5):407-415. Published online October 1, 2004
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Abstract
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- BACKGROUND
Oxidative stress contributes to vascular diseases for patients with diabetes by promoting vascular smooth muscle cell (VSMC) proliferation, monocyte/macrophage infiltration, and vascular tone alteration. As the mechanism of development and progression of diabetic vascular complications is poorly understood, this study was aimed to assess the potential role of hyperglycemia-induced oxidative stress and to determine whether thise oxidative stress is a major factor in hyperglycemia-induced migration and proliferation of VSMCs. METHODS: Rat aortic VSMCs were incubated for 48 hours in either a normal glucose (NG, 5.5 mM) or a high glucose (HG, 30 mM) condition. We then measured the proliferation and migration of VSMCs and the superoxide production. RESULTS: The migration and proliferation of VSMCs incubated under a HG condition were markedly increased compared to the NG condition. Treatment with diphenyleneiodonium (DPI, 10 M) and superoxide dismutase (SOD, 500 U/mL) significantly suppressed the HG-induced migration and proliferation of VSMCs. Superoxide production was significantly increased in the HG condition, and it was markedly decreased after a treatment with DPI and SOD. CONCLUSION: These data suggest that HG-induced VSMC migration and proliferation are related to the production of superoxide anion that is derived from NAD(P)H oxidase.
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