衰老对过氧化物酶体增殖物激活受体γ表达的影响及其与胰岛素抵抗的可能关系。
Effect of aging on the expression of peroxisome proliferator-activated receptor gamma and the possible relation to insulin resistance.
作者信息
Ye Ping, Zhang Xiu-Jin, Wang Zhao-Jun, Zhang Cheng
机构信息
Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China.
出版信息
Gerontology. 2006;52(2):69-75. doi: 10.1159/000090951.
BACKGROUND
The morbidity of insulin resistance tends to increase with aging. However, studies on molecular mechanisms underlying insulin resistance in aging process is still in paucity.
OBJECTIVE
The effect of aging on peroxisome proliferator-activated receptor gamma (PPARgamma) expression, and in addition, the possible association of PPARgamma expression with insulin resistance in aging process were investigated.
METHODS
The minimal model technique (MMT) based on frequently sampled intravenous glucose tolerance test was adopted and SI and glucose effectiveness of young and aged rats were compared. RT-PCR and Western blot were used to determine the expression of PPARgamma at mRNA and protein level in adipose tissue and skeletal muscle, as well as in human colic omentum, respectively.
RESULTS
MMT result implied existence of various degrees of insulin resistance in aged rats. The expression of PPARgamma at both mRNA and protein levels in adipose tissue of aged rats dramatically decreased; consequently, the expression of its target gene lipoprotein lipases mRNA also markedly decreased compared with those in young rats. Furthermore, the level of PPARgamma mRNA and glucose transporter-4 mRNA in skeletal muscle of aged rats attenuated significantly. The expression of PPARgamma mRNA in omental adipose tissue of old men was significantly decreased, accompanied by a tendency of higher insulin resistance index, compared with those of the young.
CONCLUSION
Aging may be associated with diminished PPARgamma expression affecting insulin resistance in the aged individuals.
背景
胰岛素抵抗的发病率往往随年龄增长而增加。然而，关于衰老过程中胰岛素抵抗潜在分子机制的研究仍然匮乏。
目的
研究衰老对过氧化物酶体增殖物激活受体γ（PPARγ）表达的影响，以及PPARγ表达与衰老过程中胰岛素抵抗的可能关联。
方法
采用基于频繁采样静脉葡萄糖耐量试验的最小模型技术（MMT），比较年轻和老年大鼠的胰岛素敏感指数（SI）和葡萄糖效能。分别用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测脂肪组织、骨骼肌以及人结肠网膜中PPARγ在mRNA和蛋白质水平的表达。
结果
MMT结果表明老年大鼠存在不同程度的胰岛素抵抗。老年大鼠脂肪组织中PPARγ的mRNA和蛋白质水平均显著降低；因此，与年轻大鼠相比，其靶基因脂蛋白脂肪酶mRNA的表达也明显降低。此外，老年大鼠骨骼肌中PPARγ mRNA和葡萄糖转运蛋白4 mRNA水平显著减弱。与年轻人相比，老年男性网膜脂肪组织中PPARγ mRNA的表达显著降低，同时胰岛素抵抗指数有升高趋势。
结论
衰老可能与PPARγ表达降低有关，影响老年个体的胰岛素抵抗。
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