OBJECTIVES: Neuromedin U (NmU) is a neuropeptide with anorexigenic activity. Two 
receptor subtypes (NmUR1 and NmUR2) confer the effects of NmU on target cells. 
We have recently demonstrated that NmU reduces insulin secretion from isolated 
pancreatic islets. Aim of our current study is to investigate the role of 
somatostatin at mediating the effects of NmU on insulin secretion.
METHODS: Expression of NmU in the pancreas was detected by immunohistochemistry. 
Insulin and somatostatin secretion from in situ perfused rat pancreas and 
isolated pancreatic islets was measured by radioimmunoassay. The paracrine 
effects of somatostatin within pancreatic islets were blocked by 
cyclosomatostatin, a somatostatin receptor antagonist.
RESULTS: Receptor subtype NmUR1, but not NmUR2, was expressed in the endocrine 
pancreas, predominantly in the periphery. Neuromedin U reduced insulin secretion 
from in situ perfused rat pancreas and stimulated somatostatin secretion from 
isolated pancreatic islets. Neuromedin U stimulated somatostatin secretion at 
both physiological and supraphysiological glucose concentrations. 
Cyclosomatostatin increased insulin secretion and reduced NmU-induced inhibition 
of insulin secretion.
CONCLUSIONS: Neuromedin U reduces insulin and increases somatostatin secretion. 
Blockade of somatostatin action abolishes the inhibition of insulin secretion by 
NmU. The results of the study suggest that somatostatin mediates the inhibitory 
action of NmU on insulin secretion.