PACAP is an islet neuropeptide which contributes to glucose-stimulated insulin secretion

Biochem Biophys Res Commun. 1999 Mar 24;256(3):664-7. doi: 10.1006/bbrc.1999.0395.


Pituitary adenylate cyclase activating peptide (PACAP) is a ubiquitously distributed neuropeptide which also is localized to pancreatic islets and stimulates insulin secretion. We examined whether endogenous PACAP within the islets might contribute to glucose-stimulated insulin secretion by immunoneutralizing endogenous PACAP. Immunocytochemistry showed that PACAP immunoreactivity is expressed in nerve terminals within freshly isolated rat islets, but not in islets that had been cultured for 48 h. In contrast, islet endocrine cells did not display PACAP immunoreactivity. Addition of either of two specific PACAP antisera markedly inhibited glucose (11.1 mmol/l)-stimulated insulin secretion from freshly isolated rat islets, whereas a control rabbit serum did not affect glucose-stimulated insulin secretion. In contrast, the PACAP antisera had no effect on glucose-stimulated insulin secretion in cultured islets. Based on these results we therefore suggest that PACAP is an islet neuropeptide which is required for the normal insulinotropic action of glucose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Glucose / antagonists & inhibitors
  • Glucose / pharmacology*
  • Immune Sera / immunology
  • Immunohistochemistry
  • In Vitro Techniques
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / chemistry
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / innervation
  • Islets of Langerhans / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Nerve Fibers / chemistry
  • Nerve Fibers / metabolism
  • Neuropeptides / analysis
  • Neuropeptides / immunology
  • Neuropeptides / metabolism
  • Neuropeptides / physiology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Presynaptic Terminals / chemistry
  • Presynaptic Terminals / metabolism
  • Radioimmunoassay
  • Time Factors


  • Adcyap1 protein, mouse
  • Immune Sera
  • Insulin
  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Glucose