title: 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.
abstract: 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.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510.
authors.forename: A
authors.initials: A
authors.lastname: Reetz
authors.forename: M
authors.initials: M
authors.lastname: Solimena
authors.forename: M
authors.initials: M
authors.lastname: Matteoli
authors.forename: F
authors.initials: F
authors.lastname: Folli
authors.forename: K
authors.initials: K
authors.lastname: Takei
authors.forename: P
authors.initials: P
authors.lastname: De Camilli
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D002478:Cells, Cultured; D005968:Glutamate Decarboxylase / Q000032:analysis*; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013572:Synaptic Vesicles / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000276:immunology / Q000378:metabolism*
chemical_list: D000906:Antibodies; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase