Localization of gamma-aminobutyric acid and glutamic acid decarboxylase in the pancreas of the nonobese diabetic mouse

Glutamic acid decarboxylase (GAD), among other potential autoantigens, is thought to play a crucial role in type I diabetes, particularly in a spontaneous model of the disease, the nonobese diabetic (NOD) mouse. In the pancreas, the presence of GAD and gamma-aminobutyric acid (GABA), the decarboxyla...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 1996-08, Vol.137 (8), p.3497-3506
Main Authors: Saravia-Fernandez, F, Faveeuw, C, Blasquez-Bulant, C, Tappaz, M, Throsby, M, Pelletier, G, Vaudry, H, Dardenne, M, Homo-Delarche, F
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - pathology
Female
gamma-Aminobutyric Acid - metabolism
Glutamate Decarboxylase - metabolism
Immunohistochemistry
Islets of Langerhans - pathology
Isoantibodies
Male
Mice
Mice, Inbred C57BL
Mice, Inbred NOD - metabolism
Neuropeptide Y - metabolism
Pancreas - metabolism
Reference Values
T-Lymphocytes - pathology
Tissue Distribution
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Summary:Glutamic acid decarboxylase (GAD), among other potential autoantigens, is thought to play a crucial role in type I diabetes, particularly in a spontaneous model of the disease, the nonobese diabetic (NOD) mouse. In the pancreas, the presence of GAD and gamma-aminobutyric acid (GABA), the decarboxylation product of GAD and a putative neurotransmitter in the islets of Langerhans, is well documented in the beta-cells. This is particularly true in rats, in which another GABAergic structure exists near the islets, the neuronal bodies. In this study, first the GABA content was measured in isolated islets from NOD and C57BL/6 mice (controls), and a decrease was found in NOD females as their insulitis progressed. Second, for the first time in mice, confocal analysis of immunofluorescent-labeled pancreatic sections revealed near the islets neuronal structures in which GAD and neuropeptide Y were colocalized, as they are in the brain. These structures were always observed in the pancreata of both sexes of C57BL/6 mice at the various ages investigated. In NOD mice, however, these neuronal structures were only detected in young females ( < 10 weeks old) and in males until an intermediate age. Moreover, patches of T cells surrounding GAD-containing fibers were seen in the vicinity of the islets with incipient periinsulitis.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.137.8.3497