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PACAP is expressed in secretory granules of insulin and glucagon cells in human and rodent pancreas - Evidence for generation of cAMP compartments uncoupled from hormone release in diabetic islets

Portela-Gomes, GM; Lukinius, A; Ljungberg, Otto LU ; Efendic, S; Ahrén, Bo LU and Abdel-Halim, SM (2003) In Regulatory Peptides 113(1-3). p.31-39
Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) is an islet neuropeptide with potent insulinotropic action. The current study investigates PACAP expression in normal human and rat pancreatic islets, and whether it is altered in diabetic state. To that end, PACAP immunoreactivity was studied by immunofluorescence methods enhanced by the catalyzed reporter deposition (CARD) technique. Insulin and cyclic adenosine monophosphate (cAMP) generation induced by PACAP were investigated in islets isolated from the spontaneously diabetic Goto-Kakizaki (GK) rat. PACAP immunoreactivity was observed in virtually all insulin and glucagon cells in both species, but not in somatostatin or pancreatic polypeptide (PP) cells; this co-localization... (More)
Pituitary adenylate cyclase-activating polypeptide (PACAP) is an islet neuropeptide with potent insulinotropic action. The current study investigates PACAP expression in normal human and rat pancreatic islets, and whether it is altered in diabetic state. To that end, PACAP immunoreactivity was studied by immunofluorescence methods enhanced by the catalyzed reporter deposition (CARD) technique. Insulin and cyclic adenosine monophosphate (cAMP) generation induced by PACAP were investigated in islets isolated from the spontaneously diabetic Goto-Kakizaki (GK) rat. PACAP immunoreactivity was observed in virtually all insulin and glucagon cells in both species, but not in somatostatin or pancreatic polypeptide (PP) cells; this co-localization pattern was unaltered in diabetic pancreata. In normal human pancreas, PACAP was further localized ultrastructurally to the secretory granules of insulin and glucagon cells. PACAP significantly potentiated glucose-stimulated insulin release in isolated islets of normal but not of GK rats. PACAP failed to enhance cAMP generation in normal islets, but induced similar to 5-folds exaggeration in the diabetic islets. In conclusion, using improved immunocytochemistry techniques and electron microscopy (EM), PACAP was shown to be expressed both in normal and diabetic islet cells and localized to secretory granules of insulin and glucagon cells. Furthermore, the insulinotropic action of PACAP was markedly impaired in diabetic islets in spite of exaggerated cAMP response. (C) 2003 Elsevier Science B.V. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
human, type-2 diabetes, pancreas, PACAP, cAMP, experimental diabetes
in
Regulatory Peptides
volume
113
issue
1-3
pages
31 - 39
publisher
Elsevier
external identifiers
  • wos:000182628300004
  • pmid:12686458
  • scopus:0037447728
ISSN
1873-1686
DOI
10.1016/S0167-0115(02)00295-1
language
English
LU publication?
yes
id
71c724ba-72e0-4a5a-8673-3195dad9e02d (old id 312404)
date added to LUP
2007-09-20 11:45:47
date last changed
2018-05-29 10:54:17
@article{71c724ba-72e0-4a5a-8673-3195dad9e02d,
  abstract     = {Pituitary adenylate cyclase-activating polypeptide (PACAP) is an islet neuropeptide with potent insulinotropic action. The current study investigates PACAP expression in normal human and rat pancreatic islets, and whether it is altered in diabetic state. To that end, PACAP immunoreactivity was studied by immunofluorescence methods enhanced by the catalyzed reporter deposition (CARD) technique. Insulin and cyclic adenosine monophosphate (cAMP) generation induced by PACAP were investigated in islets isolated from the spontaneously diabetic Goto-Kakizaki (GK) rat. PACAP immunoreactivity was observed in virtually all insulin and glucagon cells in both species, but not in somatostatin or pancreatic polypeptide (PP) cells; this co-localization pattern was unaltered in diabetic pancreata. In normal human pancreas, PACAP was further localized ultrastructurally to the secretory granules of insulin and glucagon cells. PACAP significantly potentiated glucose-stimulated insulin release in isolated islets of normal but not of GK rats. PACAP failed to enhance cAMP generation in normal islets, but induced similar to 5-folds exaggeration in the diabetic islets. In conclusion, using improved immunocytochemistry techniques and electron microscopy (EM), PACAP was shown to be expressed both in normal and diabetic islet cells and localized to secretory granules of insulin and glucagon cells. Furthermore, the insulinotropic action of PACAP was markedly impaired in diabetic islets in spite of exaggerated cAMP response. (C) 2003 Elsevier Science B.V. All rights reserved.},
  author       = {Portela-Gomes, GM and Lukinius, A and Ljungberg, Otto and Efendic, S and Ahrén, Bo and Abdel-Halim, SM},
  issn         = {1873-1686},
  keyword      = {human,type-2 diabetes,pancreas,PACAP,cAMP,experimental diabetes},
  language     = {eng},
  number       = {1-3},
  pages        = {31--39},
  publisher    = {Elsevier},
  series       = {Regulatory Peptides},
  title        = {PACAP is expressed in secretory granules of insulin and glucagon cells in human and rodent pancreas - Evidence for generation of cAMP compartments uncoupled from hormone release in diabetic islets},
  url          = {http://dx.doi.org/10.1016/S0167-0115(02)00295-1},
  volume       = {113},
  year         = {2003},
}