Is Type II diabetes mellitus a disease of the innate immune system?
Is Type II diabetes mellitus a disease of the innate immune system?
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DOI：
10.1007/s001250051058
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发表时间：
1998-10-01
期刊：
影响因子：
8.2
通讯作者：
Crook, MA
中科院分区：
文献类型：
--
作者：
Pickup, JC;Crook, MA
II型（非胰岛素依赖型）糖尿病与急性期反应标志物（包括唾液酸、α-1酸性糖蛋白、血清淀粉样蛋白A、C-反应蛋白和皮质醇）以及反应的主要细胞因子介体白细胞介素-6的血药浓度增加相关。II型糖尿病中常见的血脂异常（高脂血症和低血清HDL胆固醇水平）也是自然和实验性急性期反应的特征。我们回顾的证据表明，一个长期的甘氨酸介导的急性相反应发生在II型糖尿病，是一个广泛的先天免疫反应的一部分。通过细胞因子对脑、肝、内皮、脂肪组织和其他部位的作用，这一过程可能是代谢综合征X的生化和临床特征的主要贡献者（葡萄糖耐受不良、血脂异常、胰岛素抵抗、高血压、向心性肥胖、加速动脉粥样硬化），而且还为II型糖尿病中观察到的许多其他异常提供了机制，包括血液凝固，生殖系统、金属离子代谢、心理行为和毛细血管渗透性。在短期内，先天免疫系统恢复稳态后，环境的威胁，我们认为，在II型糖尿病和葡萄糖耐量受损的长期生活方式和环境刺激，可能在那些与先天过敏性急性期反应，产生疾病，而不是修复。
Type II (non-insulin-dependent) diabetes mellitus is associated with increased blood concentrations of markers of the acute-phase response, including sialic acid, alpha-1 acid glycoprotein, serum amyloid A, C-reactive protein and cortisol, and the main cytokine mediator of the response, interleukin-6. The dyslipidaemia common in Type II diabetes (hypertriglyceridaemia and low serum levels of HDL cholesterol) is also a feature of natural and experimental acute-phase reactions. We review evidence that a long-term cytokine-mediated acute-phase reaction occurs in Type II diabetes and is part of a wide-ranging innate immune response. Through the action of cytokines on the brain, liver, endothelium, adipose tissue and elsewhere, this process could be a major contributor to the biochemical and clinical features of metabolic syndrome X (glucose intolerance, dyslipidaemia, insulin resistance, hypertension, central obesity, accelerated atherosclerosis) but also provides a mechanism for many other abnormalities seen in Type II diabetes, including those in blood clotting, the reproductive system, metal ion metabolism, psychological behaviour and capillary permeability. In the short-term, the innate immune system restores homeostasis after environmental threats; we suggest that in Type II diabetes and impaired glucose tolerance long-term lifestyle and environmental stimulants, probably in those with an innately hypersensitive acute-phase response, produce disease instead of repair.