Regulated exocytosis and kiss-and-run of synaptic-like microvesicles in INS-1 and primary rat beta-cells.

Journal article

We have applied cell-attached capacitance measurements to investigate whether synaptic-like microvesicles (SLMVs) undergo regulated exocytosis in insulinoma and primary pancreatic beta-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 Ca(2+) entry through l-type channels. Thirty percent of SLMV exocytosis in INS-1 and rat beta-cells was associated with transient capacitance increases consistent with kiss-and-run. Elevation of intracellular cAMP (5 micromol/l forskolin) increased SLMV exocytosis 1.6-fold and lengthened the duration of kiss-and-run events in rat beta-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 Ca(2+) 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 beta-cell SLMVs in a synaptic-like function of rapid intra-islet signaling.

Authors: MacDonald, P; Obermüller, S; Vikman, J; Galvanovskis, J; Rorsman, P

• Publication status: Published
• Journal: Diabetes
• Volume: 54
• Issue: 3
• Pages: 736-743
• Publication date: 2005-03-01
• DOI: 10.2337/diabetes.54.3.736
• EISSN: 1939-327X
• ISSN: 0012-1797
• Language: English
• Keywords: Exocytosis; Secretory Vesicles; Islets of Langerhans; Forskolin; Animals; Rats; Calcium; Insulinoma; gamma-Aminobutyric Acid; Cell-Free System; Cell Membrane; Glucose; Cell Line, Tumor; Calcium Channels