title: Vasoactive intestinal polypeptide and pituitary adenylate cyclase activating polypeptide: effects on insulin release in isolated mouse islets in relation to metabolic status and age.
abstract: Obesity and development of the metabolic syndrome is related to an increased parasympathetic tone and hyperinsulinemia. We have now studied the effects of age and metabolic status on glucose-induced insulin release stimulated by the neuropeptides vasoactive intestinal polypeptide (VIP; 10 nM) and pituitary adenylate cyclase activating polypeptide (PACAP; 10 nM), that are constituents of the parasympathetic nerves in the islets, and the cholinergic agonists acetylcholine (ACh; 10 microM) and carbachol (10 microM), in isolated islets from female obese ob/ob mice and lean mice. Both VIP and PACAP enhanced insulin secretion in islets from 4-week-old hyperglycemic ob/ob mice. VIP did not increase 11.1 mM glucose-induced insulin release in islets from 4-week-old lean normoglycemic mice and neither did PACAP in the absence of bicarbonate. The neuropeptides increased insulin release in islets from 9 to 10-month-old mice but VIP and PACAP had no effect in islets from very old mice. ACh had no effect in islets from 9 to 10-months and older ob/ob mice in the absence of bicarbonate. The combination of VIP and cholinergic agonists had an additive effect in islets from ob/ob mice, and PACAP combined with carbachol potentiated insulin release in islets from 4-week-old lean mice. VIP increased early phase insulin release in perifused islets from young mice. A higher concentration of theophylline was needed to potentiate glucose-induced insulin release in islets from young lean mice than in islets from old lean mice and ob/ob mice. The present results demonstrate age-related dynamics in the effects of neuropeptides affecting cAMP in pancreatic islets. We suggest that VIP and PACAP contribute to the developing metabolic syndrome in ob/ob mice by aggravating hyperinsulinemia.
authors.affiliation: Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, SE-901 87 Umeå, Sweden. Solveig.Persson-Sjogren@histocel.umu.se
authors.forename: Solveig
authors.initials: S
authors.lastname: Persson-Sjögren
authors.forename: Sture
authors.initials: S
authors.lastname: Forsgren
authors.forename: Per
authors.initials: P
authors.lastname: Lindström
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004734:Energy Metabolism; D005260:Female; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D018721:Muscarinic Agonists / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: D007328:Insulin; D018721:Muscarinic Agonists; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D002217:Carbachol