GAD Expression in Pancreatic β-Cells

GAD is an enzyme that catalyzes the formation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) from glutamic acid. The two isoforms of GAD, GAD65 and GAD67, are encoded by two nonallelic genes located on different chromosomes, human chromosomes 2 and 10, respectively (1). In the central nervous system, both GAD65 and GAD67 are widely expressed in neurons (2). However, there is a considerable variation in the expression of the two isoforms of GAD in the pancreatic islets of humans and animals (3). In humans, GAD65 is the predominant isoform expressed in the islet cells, whereas GAD67 is present at very low levels or not at all. In rats, both isoforms of GAD are expressed in the islets, whereas GAD67 is the major isoform expressed in the islets of mice.

GAD is known to be a major pancreatic β-cell autoantigen recognized by humoral and cellular immune components in both human and murine type 1 diabetes (47). The presence of anti-GAD antibodies in the sera is a predisposing factor for the development of diabetes, and GAD-reactive T-cells, including CD4+ and CD8+ T-cells, have also been identified in patients with type 1 diabetes



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