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Glucose dependence of insulinotropic actions of pituitary adenylate cyclase-activating polypeptide in insulin-secreting INS-1 cells.

Rosengren, Anders LU ; Filipsson, K; Jing, Xingjun LU ; Reimer, M K and Renström, Erik LU (2002) In Pflügers Archiv 444(4). p.556-567
Abstract
The cAMP-elevating pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates insulin release in pancreatic B-cells. Here, we have investigated its potentiating action in rat insulinoma INS-1 cells. In intact cells, PACAP-27 (100 nM) stimulated glucose-induced insulin secretion by >60%. Using the patch-clamp technique with single-cell exocytosis monitored as increases in cell capacitance, we observed that at 10 mM and 20 mM extracellular glucose, PACAP-27 acted mainly by a >50% enhancement of depolarization-elicited Ca(2+) entry, whereas at low (3 mM) glucose, the predominant effect of the peptide was a twofold increase in Ca(2+) sensitivity of insulin exocytosis. The latter effect was mimicked by glucose itself in a... (More)
The cAMP-elevating pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates insulin release in pancreatic B-cells. Here, we have investigated its potentiating action in rat insulinoma INS-1 cells. In intact cells, PACAP-27 (100 nM) stimulated glucose-induced insulin secretion by >60%. Using the patch-clamp technique with single-cell exocytosis monitored as increases in cell capacitance, we observed that at 10 mM and 20 mM extracellular glucose, PACAP-27 acted mainly by a >50% enhancement of depolarization-elicited Ca(2+) entry, whereas at low (3 mM) glucose, the predominant effect of the peptide was a twofold increase in Ca(2+) sensitivity of insulin exocytosis. The latter effect was mimicked by glucose itself in a dose-dependent fashion. PACAP-27 exerts a prolonged effect on insulin secretion that is dissociated from changes of cytoplasmic cAMP. Whereas an elevation of cellular cAMP content (135%) could be observed 2 min after addition of PACAP-27, after 30 min preincubation with the peptide, cAMP concentrations were not different from basal. Yet, such pretreatment with PACAP-27 stimulated subsequent insulin release by congruent with60%. This sustained action is likely to reflect an increased degree of protein-kinase-A-dependent phosphorylation, and inhibitors of the kinase largely prevented the PACAP-mediated effects. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pflügers Archiv
volume
444
issue
4
pages
556 - 567
publisher
Springer
external identifiers
  • pmid:12136276
  • wos:000177451300013
  • scopus:0036449342
ISSN
0031-6768
DOI
10.1007/s00424-002-0866-1
language
English
LU publication?
yes
id
0bfe7c1d-1d63-4e8c-823b-f6f7e26a1b5e (old id 109563)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12136276&dopt=Abstract
date added to LUP
2007-07-19 09:32:15
date last changed
2017-01-01 06:40:06
@article{0bfe7c1d-1d63-4e8c-823b-f6f7e26a1b5e,
  abstract     = {The cAMP-elevating pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates insulin release in pancreatic B-cells. Here, we have investigated its potentiating action in rat insulinoma INS-1 cells. In intact cells, PACAP-27 (100 nM) stimulated glucose-induced insulin secretion by >60%. Using the patch-clamp technique with single-cell exocytosis monitored as increases in cell capacitance, we observed that at 10 mM and 20 mM extracellular glucose, PACAP-27 acted mainly by a >50% enhancement of depolarization-elicited Ca(2+) entry, whereas at low (3 mM) glucose, the predominant effect of the peptide was a twofold increase in Ca(2+) sensitivity of insulin exocytosis. The latter effect was mimicked by glucose itself in a dose-dependent fashion. PACAP-27 exerts a prolonged effect on insulin secretion that is dissociated from changes of cytoplasmic cAMP. Whereas an elevation of cellular cAMP content (135%) could be observed 2 min after addition of PACAP-27, after 30 min preincubation with the peptide, cAMP concentrations were not different from basal. Yet, such pretreatment with PACAP-27 stimulated subsequent insulin release by congruent with60%. This sustained action is likely to reflect an increased degree of protein-kinase-A-dependent phosphorylation, and inhibitors of the kinase largely prevented the PACAP-mediated effects.},
  author       = {Rosengren, Anders and Filipsson, K and Jing, Xingjun and Reimer, M K and Renström, Erik},
  issn         = {0031-6768},
  language     = {eng},
  number       = {4},
  pages        = {556--567},
  publisher    = {Springer},
  series       = {Pflügers Archiv},
  title        = {Glucose dependence of insulinotropic actions of pituitary adenylate cyclase-activating polypeptide in insulin-secreting INS-1 cells.},
  url          = {http://dx.doi.org/10.1007/s00424-002-0866-1},
  volume       = {444},
  year         = {2002},
}