Pancreatic antigenic complex p64 69: involvement in regulation of insulin secretion and relation to glutamic acid decarboxylase

Zlobina, E N; Дубинкин, И. В.; Merkushov, Alexei V.; Volynskaya, Nadia A.; G, Gudima

doi:10.1016/0165-2478(92)90129-c

Cited by 5 publications

(2 citation statements)

References 22 publications

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“…The GABA produced by GAD appears to be involved in the regulation of glucagon secretion in the islets and may have other physiological roles as well 21 ) . In isolated pancreatic islet-cell cultures, synthesis of GAD was increased according to glucose concentration 22 , 23 ) and GAD-associated antibodies have been described as having an inhibitory effect on islet insulin secretion 24 ) . These findings emphasize the potential role of GAD in the pathogenesis of IDDM and make it important to characterize its biological function in the islets and to elucidate its potential pathogenic involvement in beta-cell destruction.…”

Section: Discussionmentioning

confidence: 99%

Relationship among 64k Autoantibodies, Pancreatic β-cell Function, HLA-DR Antigens and HLA DQ Genes in Patients with Insulin-Dependent Diabetes Mellitus in Korea

Lee

Nam

et al. 1995

Korean J Intern Med

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ObjectivesAmong autoantibodies detected in patients with insulin-dependent diabetes mellitus(IDDM), antibodies to 64,000Mr islet protein(64k), now recognized as glutamic acid decarboxy lase(GAD), appear to be an even more predictive marker of IDDM than islet cytoplasmic antibody(ICA) or insulin autoantibody(IAA). We examined the relationships among 64k autoantibodies, pancreatic β-cell function, HLA-DR antigens and HLA-DQ genes in patients with IDDM in Korea.MethodsTo identify the 64k autoantibody, the immunoprecipitation method was performed for 35 patients with IDDM and 10 normal controls. In patients with IDDM, serum C-peptide levels were measured and HLA-DR typings and HLA-DQA1 and DQB1 gene typings were performed.Results12 of 35(34%) patients with IDDM were positive for 64k autoantibody in contrast to none of 10(0%) normal controls. There were no differences in residual pancreatic β-cell function between 64k autoantibody positive and negative groups. 64k autoantibody was detected more frequently in patients with recent(duration< 6 months, 10/25[40%]) and young -aged(age< 15 years, 7/18[39%]) onset of IDDM. All of 3(100%) patients with HLA-DR3/DR4 heterotypes were positive in 64k autoantibody, in contrast to 1 of 7(14%) patients without HLA-DR3 nor DR4. The frequencies of HLA-DQA1*0301, HLA-DQB1*0201, DQB1*0302 and DQB1*0303 gene types were higher in patients with 64k autoantibody (12/12[100%]) vs. without 64k autoantibody 18/22[81%], 5/11[45%] vs. without 64k autoantibody 5/22[23%], 5/11[45%] vs. without 64k autoantibody 8/22[36%] and 6/11[55%] vs. without 64k autoantibody 9/22[41%].ConclusionsThere results suggest that 64k autoantibodies have some relationship with HLA-DR, DQA1 and DQB1 genes, but not with residual pancreatic β-cell function in Korean patients with IDDM.

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Section: Discussionmentioning

confidence: 99%

Relationship among 64k Autoantibodies, Pancreatic β-cell Function, HLA-DR Antigens and HLA DQ Genes in Patients with Insulin-Dependent Diabetes Mellitus in Korea

Lee

Nam

et al. 1995

Korean J Intern Med

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“…Other factors indicate that GAD might play a role in the pathogenesis of IDDM. Mononuclear cells from IDDM patients recently have been demonstrated to proliferate in response to GAD (10), GAD-associated antibodies have been described to have an inhibitory effect on islet insulin secretion (11), and SMS, a rare neurological disorder characterized by GAD autoantibodies, often is associated with IDDM (12). These findings emphasize the potential role of GAD in the pathogenesis of IDDM and make it important to characterize its biological function in the islets and to elucidate its potential pathogenic involvement in p-cell destruction.…”

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confidence: 99%

Recombinant Glutamic Acid Decarboxylase (Representing the Single Isoform Expressed in Human Islets) Detects IDDM-Associated 64,000-Mr Autoantibodies

et al. 1992

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GAD is an autoantigen in IDDM. Molecular cloning and specific antibodies allowed us to demonstrate that only the lower M r GAD64 isoform is expressed in human islets, in contrast to human brain, rat islets, and rat brain, all of which express both GAD64 and GAD67. Expression of the human islet GAD64 isoform in COS-7 and BHK cells resulted in an enzymatically active rGAD64, which is immunoreactive with diabetic sera comparable with that of the islet 64,000-Af r autoantigen. Immunoprecipitation analyses showed that 21/28 (75%) IDDM sera had rGAD64 antibodies compared with only 1/59 (1.7%) of the healthy control sera. In immunoblot analyses, an SMS serum-but only 1/10 randomly selected IDDM sera-recognized the blotted rGAD64 without relation to immunoprecipitation titers. In conclusion, only the GAD64 isoform is expressed in human islets, in contrast to rat islets, which also express the GAD67 isoform. The immunological properties of human rGAD64 are comparable with the native 64,000-M r islet autoantigen, allowing further studies of the immunopathogenesis of IDDM. Diabetes 41:1355-59, 1992

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A convulsant, 3-mercaptopropionic acid, decreases the level of GABA and GAD in rat pancreatic islets and brain

et al. 1995

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To investigate the properties of the gamma-aminobutyric acid (GABA) synthesizing enzyme, glutamate decarboxylase (GAD), in the brain and the pancreatic islets of the rat, GABA concentration in the brain and the pancreatic islets was measured after intraperitoneal administration of 3-mercaptopropionic acid (3-MP) at 25 mg/kg. 60 min after the administration of 3-MP, GABA concentration in the hypothalamus, the superior colliculus and the hippocampus of the brain decreased by 20-30% and in the pancreatic islets by 35%. The concentration in the pancreatic acini did not change. Western blotting showed that GAD activity in the pancreatic islets decreased after administration of 3-MP compared to the control. The activity of GAD in the pancreatic islets as well as brain can be modified by a convulsant, in this case 3-MP. These results suggest the properties of GAD may be similar in the pancreatic islets and brain.

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Pancreatic antigenic complex p64 69: involvement in regulation of insulin secretion and relation to glutamic acid decarboxylase

Cited by 5 publications

References 22 publications

Relationship among 64k Autoantibodies, Pancreatic β-cell Function, HLA-DR Antigens and HLA DQ Genes in Patients with Insulin-Dependent Diabetes Mellitus in Korea

Relationship among 64k Autoantibodies, Pancreatic β-cell Function, HLA-DR Antigens and HLA DQ Genes in Patients with Insulin-Dependent Diabetes Mellitus in Korea

Recombinant Glutamic Acid Decarboxylase (Representing the Single Isoform Expressed in Human Islets) Detects IDDM-Associated 64,000-Mr Autoantibodies

A convulsant, 3-mercaptopropionic acid, decreases the level of GABA and GAD in rat pancreatic islets and brain

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