GABA and pancreatic β-cells: Colocalization of glutamic acid decarboxylase (GAD) and GABA with synaptic-like microvesicles suggests their role in GABA storage and secretion

GABA, a major inhibitory neurotransmitter of the brain, is also present at high concentration in pancreatic islets. Current evidence suggests that within islets GABA is secreted from β-cells and regulates the function of mantle cells (α- and δ-cells). In the nervous system GABA is stored in, and secreted from, synaptic vesicles. The mechanism of GABA secretion from β-cells remains to be elucidated. Recently the existence of synaptic-like microvesicles has been demonstrated in some peptide-secreting endocrine cells. The function of these vesicles is so far unknown. The proposed paracrine action of GABA in pancreatic islets makes β-cells a useful model system to explore the possibility that synaptic-like microvesicles, like synaptic vesicles, are involved in the storage and release of non-peptide neurotransmitters. We report here the presence of synaptic-like microvesicles in β-cells and in β-cell lines. Some β-cells in culture were found to extend neurite-like processes. When these were present, synaptic-like microvesicles were particularly concentrated in their distal portions. The GABA synthesizing enzyme, glutamic acid decarboxylase (GAD), was found to be localized around synaptic-like microvesicles. This was similar to the localization of GAD around synaptic vesicles in GABA-secreting neurons. GABA immunoreactivity was found to be concentrated in regions of β-cells which were enriched in synaptic-like microvesicles. These findings suggest that in β-cells synaptic-like microvesicles are storage organelles for GABA and support the hypothesis that storage of non-peptide signal molecules destined for secretion might be a general feature of synaptic-like microvesicles of endocrine cells.