期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 317, 期 2, 页码 E411-E420出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00166.2019
关键词
gp130; interleukin-6; interleukin-6 receptor; type 2 diabetes
资金
- Bundesministerium fur Bildung und Forschung (BMBF)
- Cluster of Excellence Inflammation at Interfaces of the Deutsche Forschungsgemeinschaft (DFG)
Serum levels of interleukin-6 (IL-6) are increased in patients with type 2 diabetes (T2D). IL-6 exerts its pleiotropic effects via the IL-6 alpha-receptor (IL-6R). which exists in membrane-bound and soluble (sIL-6R) forms and activates cells via the beta-receptor glycoprotein 130 (gp130). The nonsynonymous single-nucleotide polymorphism (SNP) rs2228145 (Asp358AIa) within the IL6R locus is associated with T2D. The aim of this study was to determine whether sIL-6R in combination with soluble gp130 (sgp130) is able to form an IL-6-neutralizing buffer in healthy subjects and whether this is disturbed in T2D. We found that sIL-6R-sgp130 indeed forms an IL-6-neutralizing buffer in the serum of healthy humans, whose capacity is controlled by the SNP of the IL-6R. Circulating sIL-6R-sgp130 levels were lower in T2D subjects (P < 0.001), whereas IL-6 was high and inversely correlated with sIL-6R (r = -0.57, P < 0.001), indicating a severe disturbance of the buffer. This phenomenon is also observed in sex- and age-matched patients with both T2D and atherosclerosis but not in patients with atherosclerosis alone. In conclusion, sIL-6R and sgp130 serum levels were significantly lower in T2D patients compared with healthy subjects or atherosclerosis patients, although IL-6 levels were high. These data suggest that disturbance of the protective buffer may be closely associated with T2D pathophysiology.
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