Autoantibodies against β1-adrenoceptor induce blood glucose enhancement and insulin insufficient via T lymphocytes

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

β1‐Adrenoceptor autoantibodies increase the susceptibility to ventricular arrhythmias involving abnormal repolarization in guinea‐pigs

“…As described in our previous work (Gong et al . ), β 1 ‐AR mAbs against the 197–223 amino acid sequence from the second extracelluar loop of β 1 ‐AR ( H‐W‐W‐R‐A‐E‐S‐D‐E‐A‐R‐R‐C‐Y‐N‐D‐P‐K‐C‐C‐D‐F‐V‐T‐N‐R‐C , obtained from China Peptides Co., Ltd, Shanghai, China; which shares 100% homology between humans and guinea‐pigs) was successfully synthesized and purified. The titres of β 1 ‐AR mAbs were measured by enzyme‐linked immunosorbent assay, and results are expressed as optical density (OD) units according to published methods (Liu et al .…”

“…As described in our previous work (Gong et al 2016), β 1 -AR mAbs against the 197-223 amino acid sequence from the second extracelluar loop of β 1 -AR…”

Chrysin Induces Antidiabetic, Antidyslipidemic and Anti-Inflammatory Effects in Athymic Nude Diabetic Mice

“…it has been established that, in pro-inflammatory conditions derived from LPS stimulation or ischemic/reperfusion events, the levels of IL-1α, IL-1β, IL-6, IL-8 and IL-12 are diminished [ 8 ]. These data prompted us to use athymic mice as a model to study the antidiabetic and anti-inflammatory activities of chrysin [ 9 ].…”

Increased β1-adrenergic receptor antibody confers a vulnerable substrate for atrial fibrillation via mediating Ca2+ mishandling and atrial fibrosis in active immunization rabbit models

“…HL-1 cell lines were transferred in 90 mm dishes (ZQ0920, Shanghai Zhong Qiao Xin Zhou Biotechnology Co., Ltd., China) and cultured with the complete medium (MEM medium, Gibco, C11095500BT; 10% fetal bovine serum, Gibco, 10099-141; 100 U/ml penicillin/streptomycin, Biological Industries, 04-001-1ACS) in cell incubator with 5% CO 2 and 95% air at 37°C. Monoclonal β1-AAbs (China Peptides) were kindly gifted by Prof. Huiyu Zhao from Capital Medical University [ 31 ]. Hybridoma was performed by the fusion of splenocytes from BALB/c mice with SP2/0 myeloma cell line.…”