Electrical activity and exocytotic correlates of biphasic insulin secretion from β-cells of canine islets of Langerhans: Contribution of tuning two modes of Ca2+entry-dependent exocytosis to two modes of glucose-induced electrical activity

Abstract

Biphasic insulin secretion in response to glucose, consisting of a transient first phase followed by a progressive second phase, is well described in pancreatic islets. Using single canine beta-cells we have compared the time courses of electrical activity and insulin granule exocytosis to biphasic insulin secretion. Short trains of action potentials, similar those found during first phase insulin secretion, trigger phasic exocytosis from a small pool of insulin granules, likely an immediately releasable pool docked near voltage activated Ca(2+) channels. In contrast, plateau depolarizations to between -35 and -20 mV resembling those during second phase insulin secretion, trigger tonic exocytosis from a larger pool of insulin granules, likely a highly Ca(2+)-sensitive pool farther from Ca(2+) channels. Both phasic and tonic modes of exocytosis are enhanced by glucose, via its metabolism. Hence, in canine beta-cells two distinct components of exocytosis, tuned to two components of electrical activity, may contribute significantly to biphasic insulin secretion.