Effect of neurotensin on insulin, glucagon, and somatostatin release from isolated pancreatic islets.

The effects of neurotensin on the release of insulin, glucagon, and somatostatin were investigated in isolated pancreatic islets prepared from 3- to 4-day-old rats and maintained in culture for 48 h before use. Islets were incubated for 20 and 60 min in the presence of 3 or 23 mM glucose with or without neurotensin. In 20-min incubations at 3 mM glucose, neurotensin (10-100 nM) increased the release of insulin, glucagon, and somatostatin by 60%, 90%, and 110%, respectively. These increases were not detected in 60-min incubations. Neurotensin (100 nM) inhibited the release of both insulin (by 60-90%) and somatostatin (by 100%) which was induced by 23 mM glucose in 60-min incubations; this inhibitory effect could be detected with neurotensin at a concentration of 1 nM. Neurotensin also significantly inhibited the elevations in glucagon, insulin, and somatostatin release induced by 20 mM arginine. It is concluded that neurotensin exerts a dual effect on the endocrine pancreas in vitro: 1) at low glucose concentration and over short term (20 min) incubations, the peptide stimulates insulin, glucagon, and somatostatin release; and 2) under stimulated conditions (high glucose or arginine), neurotensin inhibits insulin, glucagon, and somatostatin release.