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 (GA BA), the decarboxylation product of GAD and a putative neurotransmitte r in the islets of Langerhans, is well documented in the beta-cells. T his 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 mic e (controls), and a decrease was found in NOD females as their insulit is progressed. Second, for the first time in mice, confocal analysis o f immunofluorescent-labeled pancreatic sections revealed near the isle ts neuronal structures in which GAD and neuropeptide Y were colocalize d, 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 invest igated. In NOD mice, however, these neuronal structures were only dete cted in young females (<10 weeks old) and in males until an intermedia te age. Moreover, patches of T cells surrounding GAD-containing fibers were seen in the vicinity of the islets with incipient periinsulitis.