- Mechanism of Impaired Endothelium-dependent Vasodilation in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats .
-
Kook Jin Chun, Seok Man Son, In Ju Kim, Chi Dae Kim, Seok Dong Yoo, Yong Ki Kim
-
Korean Diabetes J. 2002;26(1):47-57. Published online February 1, 2002
-
-
-
 Abstract
 PDF
- BACKGROUND
Impaired vascular endothelium-dependent relaxation and augmented contractile responses have been reported in several long-term animals hyperglycemia models and human diabetic patients. Since oxidative stress has been implicated as a contributor to impaired vascular function, the mechanism of an impaired endothelium-dependent vasodilation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats was investigated. METHODS: This present study was undertaken to characterize both the vascular production and the enzymatic source of the superoxide anion in the type 2 diabetic rats. RESULTS: In the thoracic aortas of OLETF rats, endothelium-dependent relaxation was markedly attenuated compared to that of the control rats (LETO, Long-Evans Tokushima Otsuka) in association with a significant increase in superoxide production (2421.39+/-07.01 nmol/min/mg). There was no difference in eNOS expression between the OLETF rats and LETO rats. The increased production of superoxide anion was significantly attenuated by diphenyleneiodonium (DPI, 10 mol/L), NAD (P)H oxidase inhibitor. In line with these results, studies using various enzyme inhibitors such as DPI, allopurinol, rotenone and L-NMMA suggest that the main source of superoxide anions in the aorta is NAD (P)H oxidase. CONCLUSION: These results suggest that enhanced NAD(P)H oxidase activity and reduced nitric oxide (NO) availability through an interaction between NO and superoxide anion contribute to the impaired endothelium-dependent vasodilation in OLETF rats.
- Study on the Mechanism of Neutrophil Adhesion to Retinal Capillary Endothelial Cells under High Glucose Condition.
-
Seok Man Son, Young Sil Lee, Chang Won Lee, Seok Dong Yoo, In Ju Kim, Yong Ki Kim
-
Korean Diabetes J. 2001;25(1):35-49. Published online February 1, 2001
-
-
-
Abstract
PDF
- BACKGROUND
Diabetic retinopathy is a leading cause of adult vision loss and blindness. Much of the retinal damage that characterizes the disease results from retinal vascular leakage and occlusion. Capillary occlusion is the result of microvascular thrombi in which erythrocytes, platelets and leukocytes each may play a major role. Thus, we investigated the pathogenesis of leukocyte stasis by exposing bovine retinal capillary endothelial cells (BRCECs) for high glucose concentration. METHODS: We examined the adhesion of neutrophils to BRCECs incubated in media containing 5.5-30 mmol/L D-glucose for 24 hours. We also measured the expression of E-selectin on endothelial cells and the activation of NF(nuclear transcription factor)-kappaB in nuclear fractions of endothelial cells by using electrophoretic mobility shift assay. RESULTS: We observed that 30 mmol/L D-glucose significantly increased the adhesion of neutrophils to BRCECs (12.5% vs. 3.0%, p<0.01) and migration of neutrophil across cultured BRCEC monolayers (41.0% vs. 21.0%, p<0.05) in respect to 5.5 mmol/L D-glucose. The expression of E-selectin was increased incubated with 30 mmol/L D-glucose compared with 5.5 mmol/L D-glucose (1.45 OD vs. 0.54 OD, p<0.01). Electrophoretic mobility shift assay of nuclear extracts of BRCECs exposed for 24 h to 30 mmol/L D-glucose revealed an intense NF-kappaB activation compared with cells cultured in 5.5 mmol/L D-glucose (8.72x104 countsxmm2 vs.1.88x104 countsxmm2, p<0.01). CONCLUSION: These results suggest that high glucose concentration promote neutrophil adhesion to the BRCECs through upregulation of cell surface expression of E-selectin, possibly depending on NF-kappaB activation and may have implications for the induction of microvasculopathy of diabetic retinopathy.
- A Case of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Associated with Amitriptyline in a Patient with Diabetic Neuropathy.
-
Young Sil Lee, Seok Dong Yoo, Young Hyun Lee
-
Korean Diabetes J. 1999;23(6):857-862. Published online January 1, 2001
-
-
-
Abstract
PDF
- Amitriptyline is an effective drug for diabetic neuropathy, but rarely cause syndrome of inappropriate antidiuretic hormone (SIADH) secondary to amitriptyline administration. We experienced a case of SIADH associated with amitriptyline in a patient with diabetic neuropathy. A 64-year-old diabetic women was admitted to the hospital because of severe general weakness and obtunded mentality. Medical history shows that she was treated with amitriptyline for peripheral painful diabetic neuropathy in the past 5 years. Her conditions were including severe hyponatremia, decreased serum osmolality, and elevated urine sodium concentrations, which is consistent with SIADH. With discontinuation of amitriptyline, fluid restriction and hypertonic saline administration, serum sodium level was normalized and general conditions improved. We experienced SIADH that was associated with amitriptyline treatment for diabetic neuropathy, thus the current report is to bring an awareness of hyponatremia in our medical community.
- Solyble ICAM-1 and BCAM-1 in Patients with NIDDM.
-
Young Min Kim, Yong Gi Kim, Seok Man Son, In Ju Kim, Seok Dong Yoo, Young Keun Choi, Chang Won Lee, Jun Hyup Ahn
-
Korean Diabetes J. 1999;23(3):315-325. Published online January 1, 2001
-
-
-
Abstract
PDF
- BACKGROUND
The development of vascular complications in diabetic patients changess their quality of life, as well as shortens their life expectancy. It has been recently discovered that the expressions of the cell adhesion molecules initiate vascular complications and have major effects on the progress of atherosclerosis. We measured soluble forms of intercelluar adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1), the immunoglobulin superfamily members of the cell adhesion molecules concerning firm adhesion and transendothelial migration during leukocyte- endothelial cell interactions to clarify their concentrations and their relation with glycemic control and plasma lipoproteins as well as differences in concentration according to the presence of diabetic microvascular complcations in non-insulin dependent diabetes mellitus (NIDDM) patients. METHODS: Serum sICAM-1and sVCAM-1 levels were measured by commercial ELISA kits in 35 NIDDM patients without overt macrovascular complications of diabetes or acute inflammation and 10 normal controls matched with body mass index and plasma lipoprotein levels. The mean age of the patient group and control group was 55.82+3.43 years and 46.30+15.15 years, respectively. Clinical characteristics and laboratory parameters such as fasting plasma glucose, HbAplasma lipoproteins and status of diabetic microvascular complications were evaluated and their relations with the levels of sICAM-1 and sVCAM-1 were analyzed. RESULTS: 1) The level of sICAM-1 in NIDDM patients was significantly higher than that of normal controls (15.79+6.21 ng/mL vs. 11.98+2.35, p<0.05). sVCAM-1 showed the trend in elevation in NIDDM patients, but had no statistical significance (p=0.053). 2) The level of soluble ICAM-1 was positively correlated with HbAlc>, and plasma triglyceride levels (r=0.38, p<0.05, r=0.36, p<0.05, respectively) and negatively correlated with HDL (r=-0.44, p<0.01) in the patient group. There were no differences in their age, sex, and the presence of hypertension with the levels of sICAM-1 and no relation between sICAM-1 level and body mass index, plasma total cholesterol, Lp (a), fasting plasma glucose, fasting plasma C-peptide levels. Plasma LDL was partially correlated with the level of sICAM-1, but failed to reveal statistical significance. sVCAM-1 level was not correlated with any parameters discussed above, but had a tendency of correlation with HbAlc level (r=0.31, p=0.06). 3) No significant correlation was noted between the levels of sICAM-1 or sVCAM-1 and the duration of diabetes. 4) Both sICAM-1 and sVCAM-1 levels were significantly higher in patients with diabetic nephropathy when compared to patients without nephropathy (21.58+7.11 ng/mL vs. 14.06+4.84 ng/mL, p<0.05, 37.51+16.91 ng/mL vs. 22.26+8.89 ng/mL, p<0.05, respectively, but such differences were not noted when patients were classifed according to the presence of retinopathy or neuropathy. 5) Both sICAM-1and sVCAM-1 levels did not correlate in the patient group or in the normal control group. CONCLUSION: These findings suggest that enhanced expression of the the endothelial cell adhesion molecules in diabetic patients can be explained by endothelial dysfunction caused by persistent hyperglycemia and dyslipidemia. Furthermore, it can be suggested that endothelial dysfunction may be initiated by diabetes itself and can be deteriorated by combined dyslipidemia. From the result of the elevated concentrations of sICAM-1 and sVCAM-1 in patients with diabetic nephropathy, we can suggest that the elevation of these cell adhesion molecules may be useful as markers in diabetic nephropathy. More selective and prospective studies are necessary in order to reveal thesignificance of these cell adhesion molecules in the pathogenesis of diabetic vascular complications.
- Elevated Levels of Soluble E-selectin and P-selectin in Patients with NIDDM.
-
Seok Dong Yoo, In Joo Kim, Yong Ki Kim
-
Korean Diabetes J. 1998;22(1):23-34. Published online January 1, 2001
-
-
-
Abstract
PDF
- BACKGROUND
Although there is wide spread agreement that patients with NIDDM are at increased risk of the premature development of atherosclerosis, it is not totally clear why this is so. This may be related to the interaction of blood leukocytes with vascular endothelium resulting from a loss of normal metabolic control. The adherence of leukocytes to the endothelium is at least partly mcdiated by cell adhesion molecules. In this study, we evaluated the level of soluble E-selectin and P-selectin in blood of normal controls and patients with NIDDM, and studied its relation to glycemic control and identifiable factors influencing the level of soluble E-selectin and P-selectin. METHODS: Serum soluble E-selectin and plasma soluble P-selectin levels were measured by ELISA method in 24 NIDDM patients without macrovascullar disease and 14 normal controls matched with age, sex and body mass index. Clinical characteristics and laboratory findings such as fasting plasma glucose, HbA1c and lipid profile were evaluated, and their relation with the levels of E-selectin and P-selectin was analized. RESULTS: 1) The levels of E-selectin and P-selectin in NIDDM patients were significantly higher than those of normal controls(55.69+21.97 vs. 42.11+13.57ng/ mL, P<0.05 for E-selectin, 41.60+20.90 vs. 27.16 +7.12ng/mL, P 0.01 for P-selectin). 2) The levels of E-selectin and P-selectin were positively correlated with the fasting plasma glucose level(r=0.400 P<0,05 for E-selectin, r=0.456 P<0.01 for P-selectin). They were also positively correlated with the levels of serum triglyceride(r=0.531 P<0.01 for E-selectin, r=0.415 P =0.05 for P-selectin) but not with the levels of serum total cholesterol, LDL and HDL cholestrol in NIDDM patients. 3) No significant correlation was noted between the levels of E-selectin or P-selectin and the duration of NIDDM. And the levels were not different according to the type of treatment. 4) E-selectin level, not P-selectin level, was significantly higher in the patients with nephropathy when compared to the patients without nephropathy. But such difference was not noted when the patients were classified according to the presence of retinopathy or neuropathy. 5) E-selectin level was positively correlated with P-selectin level in both NIDDM patients and normal controls(r=0.52, P<0.01). CONCLUSION: These findings suggest that endothelial dysfunction, revealed by increased cellular adhesion molecules, could play a role in the pathogenesis of diabetic atherosclerotic vascular disorders in NIDDM patients with increased fasting plasma glucose control and hypertriglyceridemia. In addition, elevated soluble E-selectin and P-selectin level in blood might be used as a marker of diabetic nephropathy.
- Effect of Glucose on Adherence of Neutrophils to Endothelial Cells.
-
Seok Man Son, Seok Dong Yoo, In Ju Kim, Yong Ki Kim, Hee Bag Park, Chi Dae Kim, Ki Whan Hong
-
Korean Diabetes J. 1997;21(3):262-270. Published online January 1, 2001
-
-
-
Abstract
PDF
- BACKGROUND
Accelerated atherosclerotic vascular disease is the leading cause of mortality in patients with diabetes mellitus. To clarify the mechanisms that cause macrovascular dysfunction in diabetes, we examined the effect of high glucose on the adhesion of neutrophils to the endothelial cells and release of TNF-a from cultured rabbit aortic endotheIial cells. METHODS: Rabbit aortic endothelial cells in primary culture were prepared by the collagenase digestion method. Cells were incubated for various time upto 24 hours to evaluate TNF-a response to different glucose concentrations(0, 5.5, 11, 22mmol/L). Isolated rabbit neutrophils were incubated with monolayers of rabbit aortic endothelial cells under different glucose condition. RESULTS: After 24 hrs incubation with various concentrations of glucose, neutrophil adherence to high concentration of glucose(11 and 22mM)-treated endothelium was significantly increased(46+/-7 and 64 +/-6%, respectively) compared with adhesion to low concentration of glucose(0 or 5.5mM)-treated endothelium(3l +/-5 and 30+/-3%, respectively), In addition, when TNF-a imrnunoreactivity in the culture medium was measured by enzyme-linked immunoassay after 24 hours of incubation with various concentration of glucose, the secretion of TNF-a from endothelial cells was significantly increased in a concentration-dependent manner upon exposure to high concentration of glucose, CONCLUSION: The results of this study ciemonstrate tht high concentration of glucose stimulates neutrophil adhesion to endothelial cells in association with increased production of TNF-a from endothelial cells. These results suggest that glucose directly causes increased interaction between neutrophil and endothelial cell through a TNF-a-dependent mechaniasm,
|
KDA
