Chronic effects of caerulein and secretin on the endocrine pancreas of the rat.

Secretin and caerulein increase pancreatic somatostatin content when administered chronically to rats. We examined whether this change occurs in vitro and results in altered islet hormone secretion. Pancreatic somatostatin content was increased from 0.25 +/- 0.01 (mean +/- SE) to 0.41 +/- 0.03 nmol/pancreas (P less than 0.001, n = 8) in rats treated for 10 days with caerulein (1 microgram/kg) and secretin (100 micrograms/kg) every 8 h. Somatostatin content in isolated rat pancreatic islets cultured for 10 days in medium containing caerulein and secretin (10(-9) M) was also increased (2.5 +/- 1.0 to 3.6 +/- 1.3 fmol/islet, P less than 0.02, n = 7), although islet DNA content was unchanged. Small increases in glucagon content were observed in both systems, but insulin content was not changed. Isolated perfused pancreases from peptide-treated rats and islets cultured in medium containing the two peptides exhibited significantly greater somatostatin responses to 5 mM glucose and 20 mM theophylline. Insulin responses to glucose and theophylline stimulation were not altered, although basal accumulation of insulin was greater in islet cultures with added caerulein and secretin. These results suggest that caerulein and secretin have direct actions on islet hormone synthesis with effects on hormone responses to stimulation.