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

日本年轻胰岛素抵抗男性经 Epstein-Barr 病毒转化的淋巴母细胞中的细胞胰岛素抵抗

• 批准号: 13204076
• 负责人: SARUTA Takao
• 金额: $ 22.46万
• 依托单位: Department of Internal Medicine, Keio University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13204076/
• 关键词: insulin resistance; lymphoblast; hypertension; SNP; 遺伝; インスリン受容体

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

1.我们比较了从患有代谢综合征的年轻男性和没有代谢和心血管证据的年轻男性中获得的EB病毒（EBV）转化的淋巴母细胞的葡萄糖摄取特征。在469名20-25岁男性中，10名收缩压（BP）[大于或等于]130 mmHg且有高血压家族史的男性被分配到高（H）BP组，10名BP[小于或等于]110 mmHg且无高血压家族史的男性被分配到低（L）BP组。对两组患者的多项临床和代谢特征进行检查并进行比较。将HBP和LBP受试者的外周淋巴细胞进行EBV转化，并在淋巴母细胞中比较各组葡萄糖转运蛋白（Glut）介导的葡萄糖摄取。HBP组的体重指数、空腹血糖、免疫反应性胰岛素（IRI）、基于稳态模型评估的胰岛素抵抗指数（HOMA-R）、总胆固醇和LDL-胆固醇显著高于对照组。 ...更多信息 LBP亚组（全身胰岛素抵抗）。HBP组淋巴母细胞的基线Glut介导和Glut介导的胰岛素刺激的葡萄糖摄入显着低于LBP组淋巴母细胞（细胞胰岛素抵抗）。总之，EBV转化的淋巴母细胞中的细胞胰岛素抵抗与日本年轻HBP受试者相关。在淋巴母细胞中胰岛素介导的葡萄糖摄取的净增量可能是研究代谢综合征遗传方面的有用的中间表型。我们在同一人群中检测了A基因多态性与代谢特征的关系。469名青年男性志愿者根据HBP（n=61）、LBP（n=74）和中间组（n=334）分为三组。前所述HBP组的临床和代谢特征符合代谢综合征。我们接下来检查了HBP和LBP组中候选基因A多态性的频率。在六个单核苷酸多态性（SNPs），三个显着相关的胰岛素抵抗表型。因此，我们在整个人群中研究这些SNP与代谢综合征相关参数之间的关系。在位于3 '-非翻译区的一个SNP上，80个GG基因型携带者的心率和总胆固醇、LDL-胆固醇和尿酸浓度显著高于389个AA+AG基因型携带者。总之，基因A多态性与日本年轻男性的代谢综合征相关，并与低密度脂蛋白胆固醇浓度相关。少

项目成果

Correlation of sodium-related factors with insulin sensitivity in young, lean, male offspring of hypertensive and normotensive subjects.

高血压和正常血压受试者的年轻、瘦男性后代中钠相关因素与胰岛素敏感性的相关性。

• 发表时间: 2001
• 期刊: J Hum Hypertens. 15
• 作者: Ohno Y;Suzuki H;Yamakawa H;Nakamura M;Saruta T
• 通讯作者: Saruta T

Hayashida T, Ohno Y, Otsuka K, Suzawa T, Shibagaki K, Suzuki H, Ikeda H, Saruta T.: "Salt-loading elevates blood pressure and aggravates insulin resistance in Wistar fatty rats : a possible role for enhanced Na+ -H+ exchanger activity"J Hypertens.. 19. 16

Hayashida T、Ohno Y、Otsuka K、Suzawa T、Shibagaki K、Suzuki H、Ikeda H、Saruta T.：“盐负荷会升高 Wistar 脂肪大鼠的血压并加剧胰岛素抵抗：增强 Na -H 交换剂的可能作用

Yamamoto Y, Hirose H, Saito I, Nishikai K.Saruta T.: "Adiponectin, an adipocyte-derived protein, predicts future insulin resistance : two-year follow-up study in Japanese population."J Clin Endocrinol Metab.. Jan;89(1). 87-90 (2004)

Yamamoto Y、Hirose H、Saito I、Nishikai K.Saruta T.：“脂联素是一种脂肪细胞衍生的蛋白质，可预测未来的胰岛素抵抗：在日本人群中进行的两年随访研究。”J Clin Endocrinol Metab.. Jan；

Ohno Y, Suzuki H, Yamakawa H, Nakamura M, Saruta T.: "Insulin sensitivity and calcium homeostasis in young, lean, normotensive male subjects."J Hum Hypertens.. 15. 393-399 (2001)

Ohno Y、Suzuki H、Yamakawa H、Nakamura M、Saruta T.：“年轻、苗条、血压正常男性受试者的胰岛素敏感性和钙稳态。”J Hum Hypertens.. 15. 393-399 (2001)

Ohno Y, Suzuki H, Yamakawa H, Nakamura M, Saruta T.: "Insulin sensitivity and calcium homeostasis in young, lean, normotensive male subjects"J Hum Hypertens.. 15. 393-399 (2001)

Ohno Y、Suzuki H、Yamakawa H、Nakamura M、Saruta T.：“年轻、精瘦、血压正常男性受试者的胰岛素敏感性和钙稳态”J Hum Hypertens.. 15. 393-399 (2001)