Autoantibodies against β(1)-adrenoceptor induce blood glucose enhancement and insulin insufficient via T lymphocytes

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 β(1)-adrenoceptor (β(1)-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 β(1)-AA is involved in the pathogenesis of diabetes, BALB/c or nude mice were passively immunized with monoclonal antibodies against β(1)-AR (β(1)-AR mAb). Compared with vehicle control mice, β(1)-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 β(1)-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 β(1)-AA alone. However, these effects were reversed by treatment with metoprolol or peptides of the second extracellular loop of β(1)-adrenoceptor (β(1)-AR-EC(II)). These results suggest that β(1)-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 MATERIAL: The online version of this article (doi:10.1007/s12026-015-8757-7) contains supplementary material, which is available to authorized users.