AJP - Gastrointestinal and Liver Physiology, Vol 257, Issue 6 865-G870, Copyright © 1989 by American Physiological Society
Effect of cholecystokinin on the accumulation of inositol phosphates in isolated pancreatic islets
J. Florholmen, D. Malm, B. Vonen and P. G. Burhol
Department of Medicine, University Hospital of Tromso, Norway.
Sulfated cholecystokinin octapeptide (CCK-8S) potentiated glucose-induced
secretion in isolated pancreatic islets with a maximal effect at 12 mM
glucose, whereas no effect was observed at 3.3 and 25 mM glucose. This
effect of CCK-8S was maximal at 10(-7) M. Anion-exchange fast-protein
liquid chromatography analysis of [3H]inositol phosphates derived from
islets prelabeled with myo-[3H]inositol showed that glucose induced
accumulation of the 1,4,5-isomer of inositol trisphosphate and of inositol
tetrakisphosphate. At 3.3 mM glucose, CCK-8S stimulated accumulation of
inositol trisphosphate and inositol tetrakisphosphate to levels induced by
25 mM glucose alone. The net effect of CCK-8S on the accumulation of the
inositol phosphates was maximal at 12 mM glucose and decreased at higher
glucose concentrations. At 12 mM glucose the accumulation of inositol
phosphates increased gradually up to 10(-7) M CCK-8S. This study indicates
that CCK-8S potentiates glucose-induced insulin secretion through a
mechanism involving the hydrolysis of polyphosphoinositides and the
generation of inositol phosphates. However, activation of the inositol
cycle per se did not seem to induce insulin secretion.
