Signals and pools underlying biphasic insulin secretion.
Rapid and sustained stimulation of beta-cells with glucose induces biphasic insulin secretion. The two phases appear to reflect a characteristic of stimulus-secretion coupling in each beta-cell rather than heterogeneity in the time-course of the response between beta-cells or islets. There is no evidence indicating that biphasic secretion can be attributed to an intrinsically biphasic metabolic signal. In contrast, the biphasic rise in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) induced by glucose is important to shape the two phases of secretion. The first phase requires a rapid and marked elevation of [Ca(2+)](i) and corresponds to the release of insulin granules from a limited pool. The magnitude of the second phase is determined by the elevation of [Ca(2+)](i), but its development requires production of another signal. This signal corresponds to the amplifying action of glucose and may serve to replenish the pool of granules that are releasable at the prevailing [Ca(2+)](i). The species characteristics of biphasic insulin secretion and its perturbations in pathological situations are discussed.
Henquin
Jean-Claude
JC
Unité d'Endocrinologie et Métabolisme, University of Louvain School of Medicine, UCL 55.30, B-1200 Brussels, Belgium. henquin@endo.ucl.ac.be
Ishiyama
Nobuyoshi
N
Nenquin
Myriam
M
Ravier
Magalie A
MA
Jonas
Jean-Christophe
JC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D007328:Insulin; D005947:Glucose; D002118:Calcium