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Diabetes 54:736-743, 2005
© 2005 by the American Diabetes Association, Inc.

Regulated Exocytosis and Kiss-and-Run of Synaptic-Like Microvesicles in INS-1 and Primary Rat ß-Cells

Patrick E. MacDonald1, Stefanie Obermüller1, Jenny Vikman1, Juris Galvanovskis1, Patrik Rorsman1,2, and Lena Eliasson1

1 Section of Diabetes, Metabolism and Endocrinology, Lund University, Lund, Sweden
2 Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, U.K

We have applied cell-attached capacitance measurements to investigate whether synaptic-like microvesicles (SLMVs) undergo regulated exocytosis in insulinoma and primary pancreatic ß-cells. SLMV and large dense-core vesicle (LDCV) exocytosis was increased 1.6- and 2.4-fold upon stimulation with 10 mmol/l glucose in INS-1 cells. Exocytosis of both types of vesicles was coupled to Ca2+ entry through L-type channels. Thirty percent of SLMV exocytosis in INS-1 and rat ß-cells was associated with transient capacitance increases consistent with kiss-and-run. Elevation of intracellular cAMP (5 µmol/l forskolin) increased SLMV exocytosis 1.6-fold and lengthened the duration of kiss-and-run events in rat ß-cells. Experiments using isolated inside-out patches of INS-1 cells revealed that the readily releasable pool (RRP) of SLMVs preferentially undergoes kiss-and-run exocytosis (67%), is proportionally larger than the LDCV RRP, and is depleted more quickly upon Ca2+ stimulation. We conclude that SLMVs undergo glucose-regulated exocytosis and are capable of high turnover. Following kiss-and-run exocytosis, the SLMV RRP may be reloaded with {gamma}-aminobutyric acid and undergo several cycles of exo- and endocytosis. Our observations support a role for ß-cell SLMVs in a synaptic-like function of rapid intra-islet signaling.

Address correspondence and reprint requests to Dr. Patrick E. MacDonald, Lund University, Molecular and Cellular Physiology, Tornavägen 10, BMC B11, 221 84 Lund, Sweden. E-mail: patrick.macdonald{at}mphy.lu.se


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