GABA in the islets of Langerhans

Sammanfattning: GABA (?-aminobutyric acid) is a well-known inhibitory neurotransmitter in the CNS. GABA is also present at high concentrations in the insulin-producing ?-cells in the islets of Langerhans, but its function there is less clear. GABA is believed to accumulate in SLMVs (synaptic-like microvesicles). These vesicles are different from the insulin-containing LDCVs (large dense-core vesicles). In this thesis we have developed a bioassay to detect the quantal release of GABA from pancreatic ?-cells with a high temporal resolution. By applying this technique to rat pancreatic islet cells we show that GABA is exocytosed from ?-cells in a Ca2+ dependent manner. In simultaneous measurements of the release of SLMVs and LDCVs from rat ?-cells we could confirm that GABA is released from SLMVs only. These findings led us to investigate if GABA, in analogy with its role in the CNS, functions as a signaling molecule within the islets of Langerhans. We came to the conclusion that GABA released from the ?-cells inhibits glucagon secretion from neighboring ?-cells by activation of GABAA receptors on these cells. Endogenously released GABA was also found to exert an inhibitory effect on insulin secretion. This effect is due to the activation of GABAB receptors on the ?-cells and is mediated by the protein phosphate calcineurin.