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First published online 13 July 2004
doi: 10.1242/jcs.01209

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Glycine, GABA and their transporters in pancreatic islets of Langerhans: evidence for a paracrine transmitter interplay

¹ Anatomical Institute and Centre for Molecular Biology and Neuroscience, University of Oslo, POB 1105 Blindern, N-0317 Oslo, Norway
² Department of Anatomy and Cell Biology, and Locus on Neuroscience, University of Bergen, Årstadveien 19, 5009 Bergen, Norway
³ Centro de Biologia Molecular Severo Ochoa, Facultad de Ciencias, Universidad Autonoma de Madrid, Consejo Superior de Investigaciones Cientificas, Madrid 28049, Spain
⁴ Department of Neurology and Department of Physiology, UCSF School of Medicine, 600 16th Street N272B, San Francisco, CA 94143-2140, USA

^* Author for correspondence (e-mail: vidar.gundersen{at}basalmed.uio.no)

Accepted 9 March 2004

To elucidate the possible roles of the CNS neurotransmitters glycine and GABA in neuroendocrine paracrine signalling, we investigated their localizations, and those of their transport proteins, by confocal immunofluorescence and quantitative post-embedding immuno-electron microscopy in the pancreatic islets of Langerhans. We show that A-cells contain glycine in synaptic-like microvesicles as well as in secretory granules. A-cells express the macromolecules necessary to: (1) concentrate glycine within both organelle types before release (the vesicular GABA/glycine transporter VGAT=VIAAT); and to (2) take up the transmitter from the extracellular space (the plasma membrane glycine transporter GLYT2). Also B-cells have glycine in their microvesicles and granules, but the microvesicle/cytosol ratio is lower than in A-cells, consistent with the presence of GABA (which competes with glycine for vesicular uptake) in the cytosol at a much higher concentration in B-cells than in A-cells. Both A- and B-cells contain GABA in their microvesicles and secretory granules, and the membranes of the two organelle types contain VGAT in both cell types. A-cells as well as B-cells express a plasma membrane transporter GAT3 that mediates uptake of GABA. The localization of VGAT in the cores of A-cell secretory granules, and in the secretory granule membranes in both cell types, indicates novel aspects of the mechanisms for release of glycine and GABA. The discovery that both A- and B-cells possess the molecular machinery for the evoked release of both glycine and GABA from synaptic-like microvesicles suggests that both of the principal inhibitory transmitters in the brain participate in paracrine signalling in the pancreas.

Key words: -aminobutyric acid, Glycine, Pancreas, Paracrine, Uptake

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