Exocytotic Properties of Human Pancreatic β‐cells

Pancreatic β‐cells secrete insulin in response to elevated blood glucose via Ca2+‐dependent fusion of secretory granules with the plasma membrane (regulated exocytosis). While exocytosis has been extensively investigated in rodent β‐cells, studies on human β‐cells are scarce. We have characterized the exocytotic properties of human β‐cells by insulin release measurements, carbon fiber amperometry, and capacitance measurements using the patch‐clamp technique. Voltage‐clamp depolarizations evoked capacitance increases in single β‐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 Ca2+ influx through P/Q‐type than L‐type Ca2+ channels, reflecting the relative contribution of these channels to the total Ca2+ current. Exocytosis (as monitored by capacitance or amperometric measurements) decreased during repetitive stimulation as a result of inactivation of Ca2+ channels as well as depletion of a readily releasable pool of granules. These results reveal both similarities and differences between human and rodent β‐cells.