Time and amplitude regulation of pulsatile insulin secretion by triggering and amplifying pathways in mouse islets.
Glucose-induced insulin secretion is pulsatile. We investigated how the triggering pathway (rise in beta-cell [Ca(2+)](i)) and amplifying pathway (greater Ca(2+) efficacy on exocytosis) influence this pulsatility. Repetitive [Ca(2+)](i) pulses were imposed by high K(+)+ diazoxide in single mouse islets. Insulin secretion (measured simultaneously) tightly followed [Ca(2+)](i) changes. Lengthening [Ca(2+)](i) pulses increased the duration but not the amplitude of insulin pulses. Increasing glucose (5-20 mmol/l) augmented the amplitude of insulin pulses without changing that of [Ca(2+)](i) pulses. Larger [Ca(2+)](i) pulses augmented the amplitude of insulin pulses at high, but not low glucose. In conclusion, the amplification pathway ensures amplitude modulation of insulin pulses whose time modulation is achieved by the triggering pathway.
Ravier
Magalie A
MA
Unité d'Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, UCL 55.30, Avenue Hippocrate 55, B-1200 Brussels, Belgium.
Henquin
Jean-Claude
JC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D051379:Mice
D007328:Insulin; D005947:Glucose; D002118:Calcium