The metabolic syndrome sensitizes leukocytes for glucose-induced immune gene expression
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Definitions of the metabolic syndrome (MetS) include obesity, dyslipidemia, elevated levels of fasting blood glucose, and blood pressure as criteria, but it is also known that the MetS is associated with chronic, subclinical inflammation. Hyperglycemia (fasting and postprandial) may be important in exacerbating this proinflammatory state. We aimed to assess the impact of oral glucose challenge and in vitro glucose-stimulation on gene expression and secretion of inflammatory parameters in peripheral blood leukocytes and to investigate whether presence of the MetS could “prime” leukocytes to up-regulate proinflammatory markers in response to glucose. Using quantitative real-time PCR, we could show that the expression of intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) significantly increased in peripheral blood leukocytes from “MetS” subjects (n = 39) compared to “no MetS” subjects (n = 35) 2 h after an oral glucose tolerance test (ICAM-1 +52%, TNF-α +107%, and IL-6 +38%) and also in vitro after 72 h cultivation in high-glucose medium (ICAM-1 +74%, TNF-α +71%, and IL-6 +44%). Using ELISA and Luminex technique, we further observed a trend towards increased immune mediator concentrations in the corresponding cell culture supernatants from MetS patients (ICAM-1 +21%, TNF-α +31%, and IL-6 +175%). Thus, the MetS may support peripheral inflammation by sensitizing leukocytes to up-regulate proinflammatory markers in response to glucose, which in turn increases the risk for type-2 diabetes mellitus and cardiovascular disease.
KeywordsMetS Hyperglycemia Oral glucose challenge
We would like to thank A. Neudam for performance of OGTTs; G. Gornitzka, A. Hoffmann, W. Mohné, U. Poschen, and R. Rütter for excellent technical assistance; and W. Rathmann for helpful suggestions and discussions. The work was supported by the German Federal Ministry of Health and Social Security; the German Federal Ministry of Education, Science, Research and Technology; and the Ministry of Science and Research of the State North Rhine-Westphalia.
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