Presence of neuropeptide Y and its messenger ribonucleic acid in human islets: evidence for a possible paracrine role.

Neuropeptide Y (NPY) has been shown to decrease insulin secretion from rodent islets. NPY messenger ribonucleic acid (mRNA) has been demonstrated in rat and mouse pancreatic islets. We, therefore, examined human islets for the presence of NPY-encoding mRNA and NPY-like immunoreactivity. Human pancreatic islets were obtained from cadaveric organ donors, using collagenase digestion and purification on BSA density gradients. Northern blot analysis, employing a human NPY riboprobe, revealed specific NPY-encoding mRNA in the islet. Compared to the islet, NPY message abundance was 9-fold higher in the caudate nucleus and 2.4-fold higher in the temporal lobe, but it was 75% lower in the adrenal gland. NPY-like immunoreactivity was present at 2.4 +/- 0.3 fmol/microgram protein in acid-ethanol extracts from the islets. On fast protein liquid chromatography with a reverse phase column, the majority of NPY-like immunoreactivity eluted as a peak with a retention time identical to that of porcine NPY standard. Added NPY (100 nmol/L) decreased (P = 0.001) glucose-stimulated (8 mmol/L) insulin release from the human islets by 45% in a perfusion system. Therefore, human islets synthesize substantial amounts of NPY, which could act as an intra-islet paracrine regulator.