Increased adipose tissue PC-1 protein content, but not tumour necrosis factor-alpha gene expression, is associated with a reduction of both whole body insulin sensitivity and insulin receptor tyrosine-kinase activity
Increased adipose tissue PC-1 protein content, but not tumour necrosis factor-alpha gene expression, is associated with a reduction of both whole body insulin sensitivity and insulin receptor tyrosine-kinase activity
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DOI：
10.1007/s001250050675
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发表时间：
1997-03-01
期刊：
影响因子：
8.2
通讯作者：
Trischitta, V
中科院分区：
文献类型：
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作者：
Frittitta, L;Youngren, JF;Trischitta, V
在本研究中，我们测量PC-1含量，肿瘤坏死因子（TNF）-α基因表达，胰岛素刺激胰岛素受体酪氨酸激酶活性的脂肪组织从非肥胖，非糖尿病受试者。这些参数与通过静脉内胰岛素耐量试验（K-itt值）测量的体内胰岛素作用相关。PC-1含量与K-itt值呈负相关（r =-0.5，p = 0.04），与空腹（r = 0.58，p = 0.009）和口服葡萄糖耐量试验（OGTT）120 min后的血浆胰岛素水平呈正相关（r = 0.67，p = 0.002）。此外，相对胰岛素抵抗受试者（K-itt值低于6）的脂肪组织PC-1含量高于相对胰岛素敏感受试者（K-itt值高于6）（分别为525+/-49 ng/mg蛋白vs 336+/-45，p = 0.012）。在所有测试的胰岛素浓度下，胰岛素抵抗受试者的脂肪组织胰岛素受体酪氨酸激酶活性均显著低于胰岛素敏感受试者（K-itt值分别低于或高于6）（p = 0.017，双向方差分析）。与PC-1相反，在空腹和OGTT期间120 min后，脂肪组织TNF-α mRNA含量与K-itt值和血浆胰岛素水平之间未观察到显著相关性。此外，K-itt值高于或低于6的受试者之间的TNF-α mRNA含量无差异。这些在脂肪组织中的研究，连同我们先前在骨骼肌中的研究，提高了PC-1通过调节胰岛素受体功能在非肥胖、非糖尿病受试者的胰岛素敏感性程度中发挥作用的可能性。
In the present study we measured PC-1 content, tumour necrosis factor (TNF)-alpha gene expression, and insulin stimulation of insulin receptor tyrosine-kinase activity in adipose tissue from nonobese, non-diabetic subjects. These parameters were correlated with in vivo insulin action as measured by the intravenous insulin tolerance test (K-itt values). PC-1 content was negatively correlated with K-itt values (r = -0.5, p = 0.04) and positively with plasma insulin levels both fasting (r = 0.58, p = 0.009) and after 120 min during oral glucose tolerance test (OGTT) (r = 0.67, p = 0.002). Moreover, adipose tissue PC-1 content was higher in relatively insulin-resistant subjects (K-itt values lower than 6) than in relatively insulin-sensitive subjects (K-itt values higher than 6) (525+/-49 ng/mg protein vs 336+/-45, respectively, p = 0.012). Adipose tissue insulin receptor tyrosine-kinase activity in response to insulin was significantly lower at all insulin concentrations tested (p = 0.017, by two-way analysis of variance test) in insulin-resistant than in insulin-sensitive subjects (K-itt values lower or higher than 6, respectively). In contrast to PC-1, no significant correlation was observed between adipose tissue TNF-alpha mRNA content and K-itt values, and plasma insulin levels, both fasting and at after 120 min during OGTT. Also, no difference was observed in TNF-alpha mRNA content between subjects with K-itt values higher or lower than 6. These studies in adipose tissue, together with our previous studies in skeletal muscle raise the possibility that PC-1, by regulating insulin receptor function, may play a role in the degree of insulin sensitivity in non-obese, non-diabetic subjects.