title: 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.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xi tou tiao, You An Men, Beijing, 100069, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xi tou tiao, You An Men, Beijing, 100069, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xi tou tiao, You An Men, Beijing, 100069, China.|Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Disease, No. 10 Xi tou tiao, You An Men, Beijing, 100069, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xi tou tiao, You An Men, Beijing, 100069, China.|Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Disease, No. 10 Xi tou tiao, You An Men, Beijing, 100069, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xi tou tiao, You An Men, Beijing, 100069, China.|Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Disease, No. 10 Xi tou tiao, You An Men, Beijing, 100069, China.
authors.forename: Suli
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xi tou tiao, You An Men, Beijing, 100069, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xi tou tiao, You An Men, Beijing, 100069, China. liuhr2000@126.com.|Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Disease, No. 10 Xi tou tiao, You An Men, Beijing, 100069, China. liuhr2000@126.com.
authors.forename: Huirong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001786:Blood Glucose; D002460:Cell Line; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000276:immunology / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D010179:Pancreas / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D007328:Insulin; D018342:Receptors, Adrenergic, beta-1
keywords: Autoantibody against β1-adrenoceptors; Diabetes; Hyperglycemia; Insulin secretion; T lymphocytes