Diabetes & Metabolism Journal

Volume 27(6); December 2003

Editorial

The Role of Plasma Adiponectin and Polymorphism of Adiponectin Gene in the Development of Type 2 Diabetes Mellitus.: Kee Ho Song, Joong Yeol Park; Korean Diabetes J. 2003;27(6):433-437. Published online December 1, 2003

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Abstract PDF: No abstract available.

Original Articles

Genetic Association of Adiponectin Polymorphisms with Risk of Type 2 Diabetes Mellitus.: Yun Yong Lee, Nam Seok Lee, Young Min Cho, Min Kyong Moon, Hye Seung Jung, Young Joo Park, Hong Je Park, Byoung Soo Youn, Hong Kyu Lee, Kyong Soo Park, Hyoung Doo Shin; Korean Diabetes J. 2003;27(6):438-448. Published online December 1, 2003

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Abstract PDF: BACKGROUND
Adiponectin, an adipocyte-secreted protein, is known to modulate insulin sensitivity, glucose homeostasis and the development of atherosclerosis. Recently, several single nucleotide polymorphisms (SNPs) in the adiponectin gene have been reported to be associated with type 2 diabetes and components of the insulin resistance syndrome. METHODS: The frequencies of SNP T45G and G276T of the adiponectin gene was examined in 493 unrelated type 2 diabetic and 136 non-diabetic control Korean subjects. The clinical characteristics and plasma adiponectin levels of the subjects were compared within these genotypes. RESULTS: The T allele at SNP45 was significantly more frequent in the type 2 diabetes than in the control subjects (71.6 vs. 64.3%, p=0.013). The subjects with the G/G genotype of SNP45 were at reduced risk for type 2 diabetes (OR: 0.495, 95% CI 0.246-0.995, p=0.048) compared with those having the T/T genotype. However, there were no statistically significant differences in allele the frequencies (G frequency in the control vs. the diabetic group 73.9 vs. 68.9%, p=0.106) and genotype frequencies at SNP276 between groups. The subjects with the T/T genotype at SNP45 had higher a body mass index (24.6+/- 3.1 vs. 24.1+/-2.8 kg/m2, p=0.036) and serum triglyceride levels (2.03+/-1.31 vs. 1.87+/-1.38 mmol/1, p=0.041) than the T/G+G/G genotypes in the diabetic group. Those with the T/T genotype also had lower plasma adiponectin levels than those without T/T genotype at SNP45 in the control group (6.11+/-3.10 vs. 8.24+/-4.24 g/mL, p=0.043). There was a similar trend in diabetic group, but this did not reach statistical significance (4.32+/-2.81 vs. 4.96+/-3.26 g/mL, p=0.097). The SNP276 had no association with the clinical features of insulin resistance or plasma adiponectin level. CONCLUSION: The T/T genotype of SNP45 in the adiponectin gene was associated with a low adiponectin level, high body mass index, the serum triglyceride level and risk of type 2 diabetes mellitus. The SNP276 in the adiponectin gene may not be an important determinant of insulin resistance or type 2 diabetes in Korean subjects.

Effect of VRP (Vascular Rab-GAP / TBC Domain Containing Protein) Overexpression on Vascular Endothelial Cell Functions.: Chul Hee Kim, Hideto Yonekura, Hiroshi Yamamoto; Korean Diabetes J. 2003;27(6):449-455. Published online December 1, 2003

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Abstract PDF: BACKGROUND
VRP (vascular Rab-GAP/TBC domain containing protein) is a recently discovered gene from antisense - display screening of angiogenesis- related genes. However, its function in vascular endothelial cells has not been elucidated yet. This study was performed to examine the effects of overexpression of VRP on the function of vascular endothelial cells. METHODS: VRP cDNA was cloned from polyA+ RNA from human microvascular endothelial cells, and inserted into a mammalian expression plasmid vector under the control of a CMV promotor. The constructed VRP expression vector was transfected into ECV304 cells. Then the proliferation, tube formation, and vascular endothelial growth factor (VEGF) secretion of the VRP-overexpressed cells were examined. RESULTS: The expression of VRP mRNA was about two-fold greater in the VRP-transfected cells than in the control ECV304 cells. There was, however, no significant difference in the proliferation, cord-like structure formation, and VEGF secretion between the two cell groups. CONCLUSION: These results demonstrate that VRP overexpression does not affect the proliferation, tube formation, or VEGF secretion of ECV304 cells. Further studies are needed to elucidate the functional role of VRP in endothelial cells.

The Inhibitory Effect of Epicatechin on IL-1beta -induced iNOS Expression and NO Production in RINm5F Cell.: Gyeong Ryul Ryu, Do Sik Min, Duck Joo Rhie, Shin Hee Yoon, Sang June Hahn, Myung Suk Kim, Yang Hyeok Jo, Myung Jun Kim; Korean Diabetes J. 2003;27(6):456-466. Published online December 1, 2003

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Abstract PDF: BACKGROUND
Interleukin-1beta (IL-1beta ) stimulates the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO), lead to NO-mediated insulin, which produces cell damage. Within these signal pathways, nuclear factor-kappaB (NF-kappaB) activation is crucial, with many IL-1beta -sensitive genes containing NF-kappaB binding sites in their promoter regions. The inhibitory effect of (-)epicatechin (EC), an antioxidant agent, on IL-1beta -induced NF-kappaB activation, and the subsequent iNOS expression in RINm5F cells, were examined. METHODS: RINm5F cells were pretreated with EC (0.8 mM), and then cultured with IL-1beta (10U/mL), and the iNOS mRNA and protein levels then determined by Northern and Western blots, respectively. The production of NO was measured as nitrite in the culture supernatant. The protein levels of the inhibitor of nuclear factor kappaB (IkappaB) and NF-kappaB DNA binding activity were determined by Western blot and electrophoretic mobility shift assay, respectively. Also, the promoter activity following transient transfection of the iNOS promoter-luciferase reporter genes into the cells were tested. RESULTS: EC was found to significantly reduce the IL-1beta -induced NO production, and iNOS protein and mRNA levels, and also blocked the IL-1beta -induced IkappaB protein degradation, NF-kappaB activation and iNOS promoter activity. CONCLUSION: These results suggest that EC inhibits the IL-1beta -induced iNOS expression in RINm5F cells, by interfering with the binding of the NF-kappaB to the iNOS promoter, thereby inhibiting the induction of iNOS transcription.

The Correlation Between Femoral Artery Intima-Media Thickness (IMT) and Atherosclerotic Risk Factors in Type 2 Diabetes Mellitus Patients.: Ji Hyun Lee, Ho Sang Shon, Duck Soo Chung; Korean Diabetes J. 2003;27(6):467-475. Published online December 1, 2003

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Abstract PDF: BACKGROUND
High resolution B-Mode ultrasound is increasingly used in epidemiological and clinical research to noninvasively study the atherosclerotic process in the carotid artery. An increase in the intimamedia thickness (IMT) of the carotid artery has previously been reported in patients with diabetes, compared with a control group, and is related to atherosclerotic risk factors. There have been few reports on the relationship between the IMT of the femoral artery, another large artery, and atherosclerotic risk factors in diabetic patients. The aim of the present investigation was to evaluate the relationship between the femoral artery IMT and the atherosclerotic risk factors in type 2 diabetics, and to assess if such a measurement might provide further information on the extent of the atherosclerotic disease in these patients. METHODS: The carotid and femoral IMT were measured using high resolution B-mode ultrasonography in 55 type 2 diabetes patients and 25 age- and sex-matched control subjects. The femoral artery was examined distal to the inguinal ligament, at the site the artery divides into the superficial femoral and the profound femoral arteries. At the same time, patient's characteristics, including height, weight, body mass index, blood pressure, duration of diabetes and histories of hypertension and smoking, were analyzed. Examinations of the laboratory parameters, such as serum glucose, HbA1C, lipid profile, blood urea nitrogen and serum creatinine, were included in this study. RESULTS: The carotid and femoral IMT values were significantly increased in the type 2 diabetes patients compared with the control subjects. There was a significant relationship between the IMT values of the two arteries in the diabetic patients (r=0.419, p< 0.001). In a simple regression analysis, age (r=0.534, p=0.001), systolic blood pressure (r=0.499, p=0.001), diastolic blood pressure (r=0.350, p=0.003), high density lipoprotein cholesterol (r=-0.262, p=0.037) and the serum creatinine level (r=0.280, p=0.020) were statistically significant for the femoral artery IMT value. In a multiple regression analysis, age, smoking and systolic blood pressure were statistically significant for the femoral artery IMT values in diabetic patients (R2=0.379). CONCLUSION: The femoral IMT values were significantly increased in the type 2 diabetes patients. Increases in the IMT of the femoral artery are affected by the atherosclerotic risk factors; age, smoking and blood pressure. Therefore, it is suggest that measurement of the femoral IMT, using high resolution B-mode ultrasonography, is also a useful method for the detection of macrovascular complications in type 2 diabetes patients.

Randomized Controlled Trial

The Effects of Insulin Sensitizers on the Plasma Concentrations of Adipokines in Type 2 Diabetic Patients.: Hye Seung Jung, Young Min Cho, Kyung Won Kim, Byung Soo Youn, Kang Yeol Yu, Hong Je Park, Chan Soo Shin, Seong Yeon Kim, Hong Kyu Lee, Kyong Soo Park; Korean Diabetes J. 2003;27(6):476-489. Published online December 1, 2003

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Abstract PDF: BACKGROUND
Resistin, leptin and adiponectin are proteins secreted from adipose tissue, and have been suggested to play roles in insulin sensitivity. The effects of the circulating levels of two different types of insulin sensitizer, rosiglitazone and metformin, in type 2 diabetic patients were examined to elucidate the relationship between adipokines and insulin resistance. METHODS: Thirty type 2 diabetic patients, who showed poor glycemic control when administered 4 mg glimepiride a day, without severe diabetic complications or medical illness, were randomized to receive an additional 4mg rosiglitazone or 1000 mg metformin a day. The plasma resistin, leptin and adiponectin concentrations were measured at the baseline and after 6 months of treatment. The anthropometric parameters, fasting plasma glucose, HbA1C, total cholesterol, triglyceride, HDL-cholesterol and free fatty acids were also measured. Certain single nucleotide polymorphisms of adipokine genes were also identified. RESULTS: There were no significant differences in the reductions of the plasma glucose and HbA1C levels, after 6 months of treatment, between the two groups. The plasma resistin concentrations decreased, the adiponectin significantly increased and the leptin showed a tendency to increase in the rosiglitazone group. In the metformin group, only the resistin concentration significantly increased. However, the changes in the adipokines did not correlate with the HOMA-IR in either group. The reduction in the HbA1C due to rosiglitazone was greater if the initial leptin level was high, if there was a G allele on the -420th locus of the resistin gene, or the 45th locus of the APM1 (adiponectin gene) was the T-homozygote or there was a T allele on the 276th locus of the APM1. Those due to metfromin were greater with high initial adiponectin levels. CONCLUSION: In type 2 diabetic patients, showing poor glycemic control with sulfonylurea therapy, rosiglitazone or metformin treatment changed some of the adipokine concentrations, but these changes were not clearly related with insulin resistance. Polymorphisms of certain adipokine genes seem to have a relation to the susceptibility of rosiglitazone.

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