- Plasma and urinary Vascular Endothelial Growth Factor and Diabetic Nephropathy in Type 2 Diabetes Mellitus.
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Jeong Heon Oh, Hye Jin Yoo, Soo Yeon Park, Ohk Hyun Ryu, Sang Soo Park, Soon Beom Kwon, Hee Young Kim, Ji A Seo, Kye Won Lee, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Dae Ryong Cha, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 2004;28(2):111-121. Published online April 1, 2004
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 Abstract
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- BACKGROUND
VEGF(vascular endothelial growth factor) has been implicated in the pathogenesis of neovascularization and endothelial dysfunction in diabetes mellitus. However, its precise role in diabetic nephropathy is still unknown. Our aims were to determine whether alterations of plasma and urinary VEGF levels were related to diabetic microvascular complications, especially nephropathy in type 2 diabetic patients. METHODS: 107 type 2 diabetic patients, without non-diabetic kidney diseases, and 47 healthy control subjects were studied. The urinary albumin excretion was defined as the albumin-to-creatinine ratio(ACR) in 24 hour urine samples. The study subjects were divided into four groups: a nondiabetic healthy control group(n=47), a normoalbuminuric diabetic group(ACR <30mug/mg, n=37), a microalbuminuric diabetic group(ACR 30~299mug/mg, n=37) and an overt proteinuric diabetic group(ACR=300mug/mg, n=33). The plasma and urinary VEGF levels were measured in these subjects by enzyme-linked immunosorbent assays. RESULTS: 1) The urinary VEGF concentrations were significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage(log VEGF/Cr, normoalbuminuria; 4.33+/-1.06 vs. control; 3.53+/-0.79, p=0.009). The levels of urinary VEGF excretions increased with advancing diabetic nephropathy stage. 2) The plasma and urinary VEGF levels were higher in the hypertensive diabetic than the normotensive diabetic patients. 3) In the diabetic patients, the level of plasma VEGF was positively correlated with the BUN(r=0.398, p=0.039) and urinary ACR (r=0.251, p=0.044). The level of urinary VEGF was positively correlated with the urinary ACR(r=0.645, p<0.001), and creatinine(r=0.336, p=0.009), but negatively correlated with the level of serum albumin(r=-0.557, p<0.001). Both the levels of urinary VEGF and serum creatinine were independently correlated with the urinary ACR. CONCLUSIONS: The excretion of urinary VEGF increased at a relatively earlier stage in diabetic nephropathy and was significantly correlated with the excretion of urinary albumin. These results suggested the possibility of urinary VEGF as a sensitive marker or the detection of diabetic nephropathy and in predicting disease progression.
- Effect of Protein Kinase C Inhibitor on Glucose Transporter-1 (GLUT1) Expression in Cultured Rat Mesangial Cells.
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Ie Byung Park, Dae Ryong Cha, Dong Rim Kim, Sin Gon Kim, Dong Hyun Shin, Kyung Mook Choi, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 2001;25(3):218-229. Published online June 1, 2001
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Abstract
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- BACKGROUND
Recent studies have suggested that increased glucose uptake via GLUT1 may be a major determinant of glucose utilization and extracellular matrix formation in mesangial cells. This study was to evaluate the effect of protein kinase C inhibitor on glucose transporter-1 (GLUT1) expression in cultured rat mesangial cells. METHODS: The GLUT1 expression was evaluated in mesangial cells exposed to various glucose concentrations of media (5.5 mM, 15 mM or 30 mM) and incubation times (6 hr, 24 hr or 72 hr) by semiquantitative RT-PCR and western blot analysis. The effect of protein kinase C (PKC) inhibitor, calphostin C and phorbol 12-myristate 13-acetate (PMA) on GLUT1 expression was also evaluated under the same conditions. RESULTS: The GLUT1 mRNA expressions were significantly increased in MG (15 mM) and HG (30 mM) than those in NG (5.5 mM) with incubation of 6 hr, 24 hr and 72 hr, respectively. In HG media, the GLUT1 mRNA expression with incubation of 24 hr and 72 hr were significantly increased than that with incubation of 6 hr, respectively. In HG media, the GLUT1 mRNA expressions were significantly reduced in calphostin C and PMA treated groups compared with those in untreated groups. In western blot analysis of HG media, GLUT1 proteins were identified in PMA- or calphostin C-untreated group and PMA 6 hr treated group, but not identified in PMA 24 hr treated group and in calphostin C-treated groups with incubation of 6 hr and 24 hr. CONCLUSION: PKC inhibitors decrease glucose-induced GLUT1 expression under high glucose concentration in mesangial cells. These results suggest that PKC pathway may regulate GLUT1 expression under high glucose concentration in cultured rat mesangial cells.
- Effect of Glycosaminoglycan on Proteinuria and Urinary N-acetyl- -D-Glucosaminidase Excretion in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats.
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Kyung Mook Choi, Dae Ryong Cha, Sang Youb Han, Dong Rim Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 2000;24(5):533-540. Published online January 1, 2001
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Increased loss of proteoglycan (PG) characterized by an increased loss of anionic charges in the basement membrane has been considered as one of main factors causing urinary loss of albumin. The glycosaminoglycans (GAGs) are linear polymers of repeated disaccharides and the GAG chains are covalently bound to core proteins, forming proteoglycans. It is known that urinary N-acetyl- -D-glucosaminidase (NAG) excretion is a sensitive marker of renal damage and is increased before other renal functional parameters. The aim of this study was to investigate whether GAG treatment is capable of influencing urinary protein and NAG excretion in Otsuka Long-Evans Tokushima Fatty (OLETF) rats which are known as type 2 diabetic animal model. METHODS: Fifteen male OLETF rats and twenty male Long-Evans Tokushima Otsuka (LETO) rats were used for this study. LETO rats are non-diabetic control rats. All OLETF rats were randomly assigned to 2 groups: control group (n=10) given only tap water and GAG group (n=5) feeding with GAG 10 mg/kg from 7 weeks to 55 weeks of age. Measurement of body weight, blood glucose, serum BUN and creatinine was performed periodically. 24-hour urine collection for measurement of urinary protein and NAG excretion was done at 17, 25, 37, 46, 55 weeks of age. RESULTS: 1) OLETF rats showed higher body weight, blood glucose, 24-hour urinary protein and NAG excretion compared with LETO rats. But serum concentration of BUN and creatinine were not different between OLETF and LETO rats. 2) GAG-treated OLETF rats exhibited lower urinary protein/creatinine excretion (17.48+/-0.50 vs 22.49+/-0.11 mg/mg Cr, p< 0.05) and NAG (17.40+/-5.94 vs 43.73+/- 7.44 nmol/h/mg Cr, p< 0.05) excretion compared with non-treated OLETF rats. But body weights, blood glucose, serum concentration of BUN and creatinine were not different between GAG-treated OLETF rats and non-treated OLETF rats. CONCLUSION: 1) The urinary excretion of NAG may be a possible early marker of diabetic nephropathy in OLETF rats. 2) Urinary protein and NAG excretion were decreased in the GAG-treated OLETF rats. GAG seems to have a protective effect against development of diabetic nephropathy.
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