Cellular insulin resistance in Epstein-Barr virus-transformed lymphoblasts from young insulin-resistant Japanese men

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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 … More 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