Insulin is secreted from the β-cells of the pancreatic islets by Ca2+-dependent exocytosis of large dense core vesicles (LDCVs) (Ämmälä et al., 1993), a process that is triggered by glucose-induced electrical activity (Henquin and Meissner, 1984). In response to a step elevation of glucose, insulin secretion follows a characteristic biphasic time course (Curry et al., 1968): an initial transient first phase of secretion, which is completed within 10–15 min, is followed by a slowly developing and sustained second phase. It has been estimated that the first phase of secretion is due to the rapid release of a total of 40–80 LDCVs per β-cell, after which secretion proceeds at a rate of five vesicles per β-cell per minute (Rorsman and Renström, 2003).
The Ca2+ channel density in β-cell plasma membranes is very low, only about...