Autoantibodies against β1-adrenoceptor induce blood glucose enhancement and insulin insufficient via T lymphocytesReport as inadecuate




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Immunologic Research

, Volume 64, Issue 2, pp 584–593

First Online: 06 December 2015DOI: 10.1007-s12026-015-8757-7

Cite this article as: Gong, Y., Xiong, H., Du, Y. et al. Immunol Res 2016 64: 584. doi:10.1007-s12026-015-8757-7

Abstract

Diabetes mellitus is a chronic metabolic disorder with a high morbidity and mortality, but its pathogenesis is not fully understood. An increasing amount of evidence indicates that an immune mechanism plays an important role in the pathogenesis of diabetes. We demonstrated previously that the long-term presence of autoantibodies against the second extracellular loop of the β1-adrenoceptor β1-AA could change the ratio of peripheral CD4+T-CD8+T in rats, which was accompanied by lymphocytes infiltration in the rat heart, liver, and kidneys. To investigate whether β1-AA is involved in the pathogenesis of diabetes, BALB-c or nude mice were passively immunized with monoclonal antibodies against β1-AR β1-AR mAb. Compared with vehicle control mice, β1-AA-positive BALB-c mice exhibited significantly increased blood glucose P < 0.01 and increased fasting insulin P < 0.05. However, the same changes did not occur in the nude mice. And altered islet morphology was found at week 28 in β1-AA immunization group compared with vehicle control. The basal insulin level of NIT-1 β-cells was decreased markedly P < 0.01, and the lactate dehydrogenase level was increased P < 0.01 after the administration of conditioned media from T lymphocytes that had been treated with β1-AA alone. However, these effects were reversed by treatment with metoprolol or peptides of the second extracellular loop of β1-adrenoceptor β1-AR-ECII. These results suggest that β1-AA could induce hyperglycemia in both rats and mice, and also impair insulin secretion and change islet structure. T lymphocytes may play a key role in the pathogenesis of these changes in the islets.

KeywordsAutoantibody against β1-adrenoceptors Diabetes Hyperglycemia T lymphocytes Insulin secretion AbbreviationsDMDiabetes mellitus

β1-ARΒ1-adrenoceptor

β1-AR-ECIIThe second extracellular loop of β1-AR

β1-AR mAbMonoclonal antibody against β1-AR-ECII

β1-AAAutoantibodies against the second extracellular loop of β1-AR

T1DMType 1 diabetes mellitus

T2DMType 2 diabetes mellitus

DCMDilated cardiomyopathy

IPGTTIntraperitoneal glucose tolerance test

AUCArea under the curve

LDHLactate dehydrogenase

IDFInternational Diabetes Federation

TregRegulator T cells

TeffEffector T cells

CTfhCirculating follicular helper T cells

ThHelper T cells

GK ratGoto-Kakizaki rat

HPLCHigh-performance liquid chromatography

SCSubcutaneously

ELISAEnzyme-linked immunosorbent assay

ODOptical density

IgGImmunoglobulin G fractions

ConAConcanavalin A

Electronic supplementary materialThe online version of this article doi:10.1007-s12026-015-8757-7 contains supplementary material, which is available to authorized users.

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Author: Yulin Gong - Haiyan Xiong - Yunhui Du - Ye wu - Suli Zhang - Xiao Li - Huirong Liu

Source: https://link.springer.com/







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