2004 Fiscal Year Final Research Report Summary
Cellular insulin resistance in Epstein-Barr virus-transformed lymphoblasts from young insulin-resistant Japanese men
| Project/Area Number |
13204076
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Department of Internal Medicine, Keio University School of Medicine |
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Principal Investigator |
SARUTA Takao Keio University School of Medicine, Department of Internal Medicine, Professor, 医学部, 教授 (70051571)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Matsuhiko Keio University School of Medicine, Department of Internal Medicine, Associate Professor, 医学部, 助教授 (60129608)
MORII Toshiyuki Keio University School of Medicine, Department of Internal Medicine, Instructor, 医学部, 助手 (60348654)
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| Project Period (FY) |
2001 – 2004
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| Keywords | insulin resistance / lymphoblast / hypertension / SNP |
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| Research Abstract |
1. We compared the glucose uptake characteristics of Epstein-Barr virus (EBV)-transformed lymphoblasts obtained from young men with, versus without metabolic and cardiovascular evidence of metabolic syndrome. From a population of 469 men, 20-to-25-year-old, 10 men with a systolic blood pressure (BP)【greater than or equal】130 mmHg and family history of hypertension were assigned to a high (H) BP group, and 10 with a BP【less than or equal】110 mmHg and no family history of hypertension were assigned to a low (L) BP group. Multiple clinical and metabolic characteristics were examined in both groups and compared. Peripheral lymphocytes from HBP and LBP subjects were EBV-transformed and the glucose transporter (Glut)-mediated glucose uptake from each group was compared in lymphoblasts. Body mass index, fasting glucose, immuno-reactive insulin (IRI), insulin resistance index based on a homeostasis model assessment (HOMA-R), and total and LDL-cholesterol were significantly higher in the HBP th
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an the LBP subgroup (whole-body insulin resistance). Baseline Glut-mediated and Glut-mediated insulin-stimulated glucose uptake by lymphoblasts from the HBP group were significantly lower than by lymphoblasts from the LBP group (cellular insulin resistance). In conclusion, cellular insulin resistance in EBV-transformed lymphoblasts is associated with young Japanese subjects with HBP. The net increment in Glut-mediated glucose uptake by insulin in lymphoblasts may be a useful intermediate phenotype to study genetic aspects of the metabolic syndrome.
2. We examined the relationship between gene A polymorphisms and metabolic characteristics in same population. 469 young male volunteer was classified according to HBP (n=61), LBP (n=74), or intermediate group (n=334) as. previously described. In HBP group, the clinical and metabolic characteristics were consistent with metabolic syndrome. We next examined the frequency of candidate gene A polymorphisms among HBP versus LBP groups. Among six single nucleotide polymorphisms (SNPs), three were significantly associated with an insulin-resistant phenotype. Therefore, we examined the relation between these SNPs and parameters related to metabolic syndrome in the whole population. At one SNP located on the 3'-untranslated region, heart rate and concentrations of total cholesterol, LDL-cholesterol and uric acid were significantly higher in 80 GG than in 389 AA+AG genotype carriers. In conclusion, the gene A polymorphism is associated with metabolic syndrome and related to LDL-cholesterol concentration in young Japanese men. Less
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