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脂肪細胞における肥満遺伝子とインスリン作用関連遺伝子の制御機構の研究

脂肪细胞中肥胖基因及胰岛素作用相关基因的调控机制研究

基本信息

批准号：
09671053
负责人：
NISHIMURA Haruo
金额：
$ 1.98万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

(1) Effect of thiazolidinediones on leptin production and insulin action in rat adipocytes. Thiazolidinedione, an insulin sensitizer, reduced protein and mRNA levels of leptin in rat adipocytes after 24 hours. This compound also increased 2-deoxyglucose uptake in the adipocytes. However, mRNA level of leptin and insulin action were not changed, when the adipocytes were incubated with exogenous leptin for 24 hours, Thus it is suggested that exogenous leptin dose not affect the primary culture of adipocytes directly.(2) Effect of leptin on insulin action in culture of skeletal muscle Leptin did not affect the insulin action including insulinsignaling systems and glucose uptake in culture of skeletal muscles (L6 cells).(3) Insulin action in leptin transgenic mouse Leptin transgenic mouse showed no accumulation of adipocytes, both white and brown adipocytes. In vivo insulin action determined by intraperitoneal glucose tolerance test (GTT) and insulin tolerance test (ITT) showed enhanced insulin sensitivity in the transgenic mice. It is suggested that leptin has lipoatrophic effect on adipocytes and insulin action, and that insulin action is enhanced Through central nervous systems by leptin.(4) Concentration of plasma leptin in human There were correlations between plasma leptin and % fat , body mass index significantly. And the was also gender difference in leptin concentration (male<female). However aging did not affect the concentration. We also found some polymorphisms in leptin gene, but there were no relation between leptin and the polymorphisms in Japanese obese subjects.

(1)噻唑烷二酮类化合物对大鼠脂肪细胞产生瘦素和胰岛素作用的影响。胰岛素增敏剂噻唑烷二酮可降低24小时后大鼠脂肪细胞中瘦素的蛋白和mRNA水平。该化合物还增加了脂肪细胞对2-脱氧葡萄糖的摄取。但当脂肪细胞与外源性瘦素共同孵育24小时后，瘦素的mRNA水平和胰岛素作用并未发生改变，提示外源性瘦素不会直接影响脂肪细胞的原代培养。(2)瘦素对骨骼肌瘦素培养中胰岛素作用的影响不影响骨骼肌细胞的胰岛素作用，包括胰岛素信号系统和骨骼肌细胞对葡萄糖的摄取。(3)瘦素转基因小鼠的胰岛素作用未见脂肪细胞蓄积，白色和棕色脂肪细胞均不积聚。体内葡萄糖耐量试验(GTT)和胰岛素耐量试验(ITT)显示转基因小鼠的胰岛素敏感性增强。提示瘦素对脂肪细胞具有脂肪萎缩作用和胰岛素作用，瘦素通过中枢神经系统增强胰岛素作用。(4)人血浆瘦素浓度与体脂百分比、体重指数显著相关。瘦素水平也存在性别差异(男性和女性)。然而，老化并不影响药物浓度。我们还发现了瘦素基因的一些多态性，但在日本肥胖者中，瘦素基因的多态性与瘦素基因的多态性无关。