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- Title
Glucose dependence of insulinotropic actions of pituitary adenylate cyclase-activating polypeptide in insulin-secreting INS-1 cells.
- Authors
Rosengren, A.; Filipsson, K.; Jing, X.-J.; Reimer, M. K.; Renström, E.
- 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 Ca2+ entry, whereas at low (3 mM) glucose, the predominant effect of the peptide was a twofold increase in Ca2+ 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 ≅60%. 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.
- Subjects
ADENYLATE cyclase; INSULIN; ISLANDS of Langerhans tumors; PEPTIDES; GLUCOSE; LYASES
- Publication
Pflügers Archiv: European Journal of Physiology, 2002, Vol 444, Issue 4, p556
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-002-0866-1