- Plasminogen Activator Inhibitor-1 (PAI-1)/tissue Plasminogen Activator (t-PA) Levels and PAI-1 4G/5G Promoter Polymorphism in Type 2 Diabetes with Microalbuminuria.
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Seong Hee Kwon, Young Joo Park, In Kyong Jeong, Jae Joon Koh, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee
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Korean Diabetes J. 2003;27(3):186-198. Published online June 1, 2003
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- BACKGROUND
Persistent microalbuminuria in diabetic patients is a risk factor of cardiovascular mortality. Increased plasma plasminogen activator inhibitor type-1 (PAI-1) levels have been observed in diabetic patients with overt nephropathy. However, there have been few studies on diabetic patients with microalbuminuria. The expression of PAI-1 may be influenced by the polymorphism of the PAI-1 genotype promoter. The aim of this study was to investigate the relationship between the plasma PAI-1/t-PA levels, polymorphism of the PAI-1 4G/5G promoter and microalbuminuria in type 2 diabetes. METHODS: The plasma PAI-1/t-PA levels and polymorphisms of the PAI-1 promoter were measured in type 2 diabetic patients without nephropathy (n=30), and with microalbuminuria (n=30) and overt proteinuria (n=20). The correlation between the amount of urinary albumin excretion and plasma PAI-1/t-PA levels were investigated using Pearson's correlation analyses. RESULTS: The plasma PAI-1/t-PA levels and polymorphisms of the PAI-1 promoter showed no significant difference between the three groups in relation to the urinary albumin excretion. There were no differences in the plasma PAI-1/t-PA levels between the genotypes of the polymorphism of the PAI-1 promoter. No association was found between the amount of urinary albumin excretion and the plasma PAI-1/t-PA levels and genotypes of the polymorphism of the PAI-1 promoter. CONCLUSION: These results show that there was no decrease in the fibrinolytic state in type 2 diabetics with microalbuminuria, compared to normoalbuminuria, which also suggest that polymorphisms of the PAI-1 4G/5G promoter do not affect the plasma PAI-1/t-PA levels in type 2 diabetic patients with microalbuminuria.
- Metabolic Phenotype of Glycogen Synthase Gene Inhibition in Human Skeletal Muscle Cells.
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Jae Joon Koh, Kyong Soo Park, Jeong Mi Kim, Seong Yeon Kim, Hong Kyu Lee, Theodore P Ciaraldi, Robert R Henry
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Korean Diabetes J. 2000;24(3):331-339. Published online January 1, 2001
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- BACKGROUND
Glycogen synthase (GS) is the rate-limiting enzyme controlling non-oxidative glucose disposal in skeletal muscle. Reduction in GS activity and impaired insulin responsiveness are characteristic features of skeletal muscle in type 2 diabetes that contribute to glucose intolerance. These properties also exist in human skeletal muscle cell cultures from type 2 diabetic subjects. The aim of study is to determine the effect of an isolated reduction in GS on glucose metabolism and if this change can generate a diabetes-like state. METHODS: Cultured skeletal muscle cells from non-diabetic subjects were treated with antisense oligodeoxynucleotides (ODN) to GS to interfere with expression of the gene for 6 days. GS activity, protein expression, glycogen synthesis and cellular glycogen content were measured. RESULTS: Treatment with antisense ODN reduced GS protein expression by 70% compared to control (scrambled) ODN (p<0.01). Both total GS activity and that measured at 0.1 mM G-6-P were reduced by antisense ODN treatment. Insulin responsiveness of GS was also halved. Basal GS FV0.1 was decreased in both antisense ODN and control ODN treated cells and antisense treated cells did not show increase in GS FV0.1 in response to insulin stimulation. Glucose incorporation into glycogen under basal conditions was unaltered after antisense ODN treatment, though no further stimulation in response to insulin was observed. Yet both cellular glycogen content and glycogen synthesis were lower in antisense ODN treated cells compared to control ODN treated cells. CONCLUSIONS: Reduction in GS expression in human skeletal muscle cell impair GS activity and insulin responsiveness but does not replicate the abnormalities of glycogen synthesis found in cultured diabetic skeletal muscle cells.
- Decreased Mitochondrial DNA Content in Peripheral Blood Leukocyte procedes the Development of Type 2 Diabetes Mellitus.
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Jae Joon Koh, Jong Ho Ahn, Soon Ja Kwon, Ji Hyun Song, Chan Soo Shin, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee
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Korean Diabetes J. 1998;22(1):56-64. Published online January 1, 2001
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- BACKGROUND
Mitochondrial mutations and deletions, have been implicated in the pathogenesis of diabetes mellitus. This can explain only a very small proportion of the patients with diabetes mellitus. Mitochondrial DNA(mtDNA) is vulnerable to oxidative stress, resulting in both qualitative and quantitative changes. We reported that the amount of mtBNA decreased in the peripheral blood leukocyte of patients with NIDDM. In this study, we examined that decreased mtDNA content preceded the development of NIDDM{Non-insulin dependent diabetes mellitus) and correlated with various insulin resistance parameters.In this study, we demonstrated that the amount of mtDNA decreased in peripheral blood leukocyte of patients with NIDDM. Furthermore, we found that lower mtDNA levels preceded the development of diabetes mellitus. METHODS: We utilized the stored blood samples from two community-based survey conducted in Yonchon County, Korea in 1993 and 1995. We selected 23 newly diagnosed diabetic patients and 22 age- and sex-matched control subjects. The buffy coats of peripheral blood samples were used for the competitive PCR and the products pairs were separated by gel EP. The content of mtDNA was calculated with the densitometry. RESULTS: There were no difference in the initial anthropometric parameters, blood pressure and lipid profiles between subjects who became diabetic converters and non converters. The mean quantity of mtDNA was lower in the converters, with 102.8+ 41.5 copies/pg template DNA compared to 137.8+ 67.7 copies/pg template DNA of the controls(p 0.05). The significant inverse correlations were noted between mtDNA content and WHR(r=0.31, p<0.05) in the first, and fasting glucose level(r=-0.35, p<0.05), diastolic blood pressures(r=-0.36, p<0.05), and WHR(r=-0.40, p<0.01) in the second survey. The correlations with the serum levels of total and high density cholesterol, triglyceride, insulin and proinsulin were not statistically significant. CONCLUSION: Although a relationship between diabetes and mitochondrial dysfunction has been suspected. This study showed that decreased mtDNA content in peripheral blood proceded the development of NIDDM. This is the first study to demonstrate that quantitative changes in mtDNA precede the development of NIDDM.
- The Effect of Elevated Plasma Free Fatty Acids on Non-Insulin-Mediated Glucose Uptake and Insulin Resistance.
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Yong Ki Min, Jong Ho Ahn, Jae Joon Koh, Hong Kyu Lee, Hun Ki Min
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Korean Diabetes J. 1998;22(1):47-55. Published online January 1, 2001
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- BACKGROUND
In vivo glucose uptake occurs via two mechanisms, namely insulin-mediated glucose uptake(IMGU) and non-insulin-mediated glucose up-take(NIMGU). NIMGU accaunts for about 70~85% of postabsorptive glucose uptake. Despite many studies, it is still controversial how an increase in lipolysis affects glucose metabolism in man. More specifically, the effect of free fatty acid(FFA) on NIMGU has not been exanuned. METHOD: Two-step(euglycemia- hyperglycemia) glucose clamp techique with [3-H]-glucose infusion was performed in 6 normal men. Each man was studied twice, with(test experiement) and without (control experiment) the administration of lipid and heparin at an interval of at least 4 weeks in random order. The subjects received an insulin infusion at 1.1 pmol/kg. min in conjuction with the infusion of somatostatin(step 1, 153 nmol/h; step 2, 458 nmol/h). Result: Plasma glucose levels during step 1 were 5.4+0.1 mmol/L(control experiment), 5.4+0.1 mmol/ L(test experiment), and were raised to 14.7+0.2 mmol/L, 14.6+0.1 mmol/L, respectively, during step 2. Plasma insulin levels during step 1 were 56+4 pmol/L(control experiment), 52+4 pmol/L(test experiment), and were 65+3 pmol/L, 62+4 pmol/L, respectively, during step 2. In control experiment, plasma FFA levels were 0.24+0.02 mmol/L during step 1 and 0.11+0.01 mmol/L during step 2. In test experiment, plasma FFA levels increased significantly to 1.08+0.06 mmol/L during step 1 and 1.01 +0.04 mmol/L during step 2, respectively(p<0.01). Glucose infusion rate(GIR) to increase glucose concentrations to the desired levels were 7.7+0.8 pnol/ kg,min during step 1 and 29.7+3.7 pmol/kg.min during step 2 in control experiment. In test experiment, GIR decreawd significantly to 3.8+0.9 pmol/ kg.min during step 1 and 20.7+1.2 pmol/kg.min during step 2, respectively(p<0.05). There was no significant difference between NIMGU, estimated by the difference between glucose disapperance rate of step 1 and step 2 of lipid infusion test experiment and that of control experiment. CONCLUSION: These results showed that artificial elevation of plasma FFA levels led to a state of insulin resistance, however, the change of FFA level did not influence NIMGU in man.
- Biological activity of in-vitro glycosylated insulin in diabetic patients.
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Joong Yeol Park, Jae Joon Koh, Kyong Soo Park, Moon Kyu Lee, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Hun Ki Min, Sung Wan Kim
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Korean Diabetes J. 1993;17(3):253-258. Published online January 1, 2001
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- No abstract available.
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