Exocytotic properties of human pancreatic beta-cells.
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.
Braun
Matthias
M
Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom. matthias.braun@drl.ox.ac.uk
Ramracheya
Reshma
R
Johnson
Paul R
PR
Rorsman
Patrik
P
D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004594:Electrophysiology; D005089:Exocytosis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D018408:Patch-Clamp Techniques
D015220:Calcium Channels; D007328:Insulin; D000242:Cyclic AMP