Neuropeptide Y (NPY) is a 36 amino acid peptide known to inhibit gluco
se-stimulated insulin secretion. NPY has recently been shown to be syn
thetized within rat islets of Langerhans and to be secreted in a diffe
rentiated rat insulin-secreting cell line, and as to this date the loc
alization of NPY in human endocrine pancreas has not been reported. As
NPY shares high amino acid sequence homology with peptide YY (PW) and
pancreatic polypeptide (PP), the polyclonal antibodies raised against
these peptides often cross-react with each other. To demonstrate the
presence of NPY in the human endocrine pancreas, we used a highly spec
ific monoclonal antibody raised against NPY and another against its C-
flanking peptide (CPON). We studied three cases of hyperplasia of Lang
erhans islets and 11 cases of endocrine tumors of the pancreas. NPY an
d CPON were detected in all three cases of hyperplasia. For the 11 pan
creatic tumors, five and nine of the tumors were positive for the anti
bodies NPY and CPON, respectively. The two negative tumors for CPON im
munoreactivity were differentiated insulinomas, which showed no eviden
ce of other hormonal secretion. In normal human Langerhans islet, NPY
and CPON immunoreactivities were colocalized in glucagon-producing cel
ls (cu-cells) and in a few insulin-secreting cell (p-cells). In conclu
sion, 1) NPY-specific immunoreactivity was found to be present in huma
n Langerhans islets and some tumors of the endocrine pancreas, 2) in n
ormal human Langerhans islet, NPY is predominantly present in cu-cells
and in a few beta-cells, 3) NPY may be used as a marker of the endocr
ine pancreas, and 4) the functional role of NPY within human islets of
Langerhans and plasma NPY levels in patients diagnosed with endocrine
pancreatic tumors remains to be established.