GABA and pancreatic beta‐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 beta‐cells and regulates the function of mantle cells (alpha‐ and delta‐cells). In the nervous system GABA is stored in, and secreted from, synaptic vesicles. The mechanism of GABA secretion from beta‐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 beta‐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 beta‐cells and in beta‐cells. Some beta‐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 beta‐cells which were enriched in synaptic‐like microvesicles. These findings suggest that in beta‐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.