Herder Christian, Haastert Burkhard, Müller-Scholze Sylvia, Koenig Wolfgang, Thorand Barbara, Holle Rolf, Wichmann H-Erich, Scherbaum Werner A, Martin Stephan, Kolb Hubert
German Diabetes Clinic, German Diabetes Center, Leibniz Institute at Heinrich-Heine University, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
Diabetes. 2005 Dec;54 Suppl 2:S11-7. doi: 10.2337/diabetes.54.suppl_2.s11.
Chemokines are crucial immune mediators in many physiological and pathophysiological conditions. Chemokines have been hypothesized to be involved in macrophage infiltration into adipose tissue in obesity and might therefore play an important role in the development of obesity-related disorders like type 2 diabetes. Out of 1,653 individuals aged 55-74 years participating in a population-based survey in southern Germany (the Kooperative Gesundheitsforschung in der Region Augsburg [KORA] [Cooperative Health Research in the Region of Augsburg] Survey S4, 1999-2001), 236 individuals with type 2 diabetes, 242 subjects with impaired glucose tolerance (IGT), and 244 normoglycemic control subjects were studied for circulating concentrations of interleukin (IL)-8; RANTES (regulated on activation, normal T-cell expressed, and secreted); interferon-gamma-inducible protein-10 (IP-10), and eotaxin. Systemic concentrations of RANTES were higher in individuals with IGT or type 2 diabetes than in control subjects, whereas IL-8 levels were elevated in type 2 diabetic patients only (P < 0.001 for all comparisons). IP-10 and eotaxin were not significantly associated with IGT or type 2 diabetes. Adjustment for age, sex, BMI, hypertension, LDL cholesterol, HDL cholesterol, uric acid, C-reactive protein, and IL-6 did not alter these findings. Our findings indicate that RANTES and IL-8 may be involved in the development of type 2 diabetes independent of metabolic syndrome-related risk factors and of each other. There is no general upregulation of chemokine production in type 2 diabetes, but rather an association of the disease with specific members of the chemokine family.
趋化因子是许多生理和病理生理状况下至关重要的免疫介质。据推测,趋化因子参与肥胖状态下巨噬细胞浸润脂肪组织的过程,因此可能在诸如2型糖尿病等肥胖相关疾病的发生发展中发挥重要作用。在参与德国南部一项基于人群的调查(奥格斯堡地区合作健康研究[KORA]调查S4,1999 - 2001年)的1653名55 - 74岁个体中,对236名2型糖尿病患者、242名糖耐量受损(IGT)受试者和244名血糖正常的对照受试者的白细胞介素(IL)-8、调节激活正常T细胞表达和分泌因子(RANTES)、干扰素-γ诱导蛋白10(IP - 10)及嗜酸性粒细胞趋化蛋白的循环浓度进行了研究。IGT或2型糖尿病个体的RANTES全身浓度高于对照受试者,而仅2型糖尿病患者的IL - 8水平升高(所有比较P < 0.001)。IP - 10和嗜酸性粒细胞趋化蛋白与IGT或2型糖尿病无显著相关性。对年龄、性别、体重指数、高血压、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、尿酸、C反应蛋白和IL - 6进行校正后,这些结果未改变。我们的研究结果表明,RANTES和IL - 8可能独立于代谢综合征相关危险因素且相互独立地参与2型糖尿病的发生发展。2型糖尿病中不存在趋化因子产生的普遍上调,而是该疾病与趋化因子家族的特定成员相关。