Antagonistic effect of dibutyryl cyclic GMP on caerulein induced insulin secretion in isolated perifused rat islets.

The effects of caerulein and dibutyryl cyclic GMP on isolated rat islets were studied using the perifusion system. One, 20, 50 and 100 nM caerulein stimulated insulin secretion in the perifused rat islets, in a dose dependent manner. Insulin secretion reached a maximal level in the presence of 50 nM caerulein. Caerulein-induced insulin secretion showed a predominant first and minimal second phase. After cessation of stimulation with 50 nM caerulein, the insulin secretion level did not return to the basal value, but enhanced hormone secretion was sustained to a significant extent (p less than 0.01). The simultaneous administration of 10(-3) M dibutyryl cyclic GMP, a specific membrane antagonist against cholecystokinin (CCK), inhibited the first and second phases of caerulein-induced insulin secretion. Moreover, with this nucleotide, "persistent" insulin secretion induced by 50 nM caerulein was inhibited. These data indicate that caerulein directly stimulates pancreatic B cells and that this peptide causes "persistent" insulin secretion. Dibutyryl cyclic GMP counteracts the effects of caerulein. Thus, both pancreatic B cells and pancreatic acinar cells possibly possess a CCK receptor.