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Aparicio-Siegmund, Samadhi, Garbers, Yvonne, Flynn, Charlotte M., Waetzig, Georg H., Gouni-Berthold, Ioanna, Krone, Wilhelm, Berthold, Heiner K., Laudes, Matthias, Rose-John, Stefan and Garbers, Christoph ORCID: 0000-0003-4939-6950 (2019). The IL-6-neutralizing sIL-6R-sgp130 buffer system is disturbed in patients with type 2 diabetes. Am. J. Physiol.-Endocrinol. Metab., 317 (2). S. E411 - 10. BETHESDA: AMER PHYSIOLOGICAL SOC. ISSN 1522-1555

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Aparicio-Siegmund, Samadhi UNSPECIFIED UNSPECIFIED UNSPECIFIED Garbers, Yvonne UNSPECIFIED UNSPECIFIED UNSPECIFIED Flynn, Charlotte M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Waetzig, Georg H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gouni-Berthold, Ioanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Krone, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Berthold, Heiner K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Laudes, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Rose-John, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Garbers, Christoph UNSPECIFIED orcid.org/0000-0003-4939-6950 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-145436
DOI:	10.1152/ajpendo.00166.2019
Journal or Publication Title:	Am. J. Physiol.-Endocrinol. Metab.
Volume:	317
Number:	2
Page Range:	S. E411 - 10
Date:	2019
Publisher:	AMER PHYSIOLOGICAL SOC
Place of Publication:	BETHESDA
ISSN:	1522-1555
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SOLUBLE INTERLEUKIN-6 RECEPTOR; CORONARY-HEART-DISEASE; PLASMA INTERLEUKIN-6; SUSCEPTIBILITY LOCUS; SIGNAL TRANSDUCER; GENOME-WIDE; IL-6R GENE; ATHEROSCLEROSIS; ASSOCIATION; INFLAMMATION Multiple languages Endocrinology & Metabolism; Physiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14543