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Pancreatic beta-cells secrete insulin in response to elevated blood glucose via Ca(2+)-dependent fusion of secretory granules with the plasma membrane (regulated exocytosis). While exocytosis has been extensively investigated in rodent beta-cells, studies on human beta-cells are scarce. We have characterized the exocytotic properties of human beta-cells by insulin release measurements, carbon fiber amperometry, and capacitance measurements using the patch-clamp technique. Voltage-clamp depolarizations evoked capacitance increases in single beta-cells in a time- and voltage-dependent manner. The capacitance responses as well as insulin release from intact islets were strongly amplified by elevation of intracellular cAMP levels. Exocytosis was more dependent on Ca(2+) influx through P/Q-type than L-type Ca(2+) channels, reflecting the relative contribution of these channels to the total Ca(2+) current. Exocytosis (as monitored by capacitance or amperometric measurements) decreased during repetitive stimulation as a result of inactivation of Ca(2+) channels as well as depletion of a readily releasable pool of granules. These results reveal both similarities and differences between human and rodent beta-cells.

Original publication

DOI

10.1111/j.1749-6632.2008.03992.x

Type

Journal article

Journal

Ann N Y Acad Sci

Publication Date

01/2009

Volume

1152

Pages

187 - 193

Keywords

Calcium Channels, Cells, Cultured, Cyclic AMP, Electrophysiology, Exocytosis, Humans, Insulin, Insulin-Secreting Cells, Patch-Clamp Techniques