Pituitary adenylate cyclase-activating polypeptide receptors mediating insulin secretion in rodent pancreatic islets are coupled to adenylate cyclase but not to PLC.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potentiator of glucose-induced insulin secretion. PACAP binds to a PACAP-specific receptor (PAC1) and to VPAC receptors (VPAC1 and VPAC2), which share high affinity for vasoactive intestinal polypeptide (VIP). In the present study, the molecular expression of PACAP receptor isoforms and the signaling pathways involved in the insulin secretory effect of PACAP were investigated in isolated rat and mouse pancreatic islets. mRNA encoding PAC1-short, -hop, and -very short variants, as well as VPAC1 and VPAC2, were expressed in pancreatic islets. PACAP and VIP were equipotent in potentiating glucose-induced insulin release. Both peptides were also equipotent in increasing cAMP production, but PACAP was more efficient than VIP. Unlike carbachol, PACAP and VIP had no effect on inositol phosphate production. In the PAC1-deficient mouse, the insulinotropic effect of PACAP was reduced, and its differential effect on cAMP production was abolished, whereas the effects of VIP remained unchanged. These results clearly show that the insulinotropic effect of PACAP involved both VPAC and PAC1. The PAC1 variants expressed in rat and mouse pancreatic islets seem to be coupled to adenylate cyclase but not to PLC.
Jamen
Francoise
F
Unité Propre de Recherche 9023, Centre National de la Recherche Scientifique, 34094 Montpellier Cedex 05, France.
Puech
Raymond
R
Bockaert
Joel
J
Brabet
Philippe
P
Bertrand
Gyslaine
G
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000096:biosynthesis / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000096:biosynthesis / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; C495504:Adcyap1r1 protein, mouse; C495505:Adcyap1r1 protein, rat; D007328:Insulin; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C495507:Vipr1 protein, mouse; C495508:Vipr1 protein, rat; C495510:Vipr2 protein, mouse; C495511:Vipr2 protein, rat; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases