title: Amplification of insulin secretion by acetylcholine or phorbol ester is independent of β-cell microfilaments and distinct from metabolic amplification.
abstract: Insulin secretion (IS) triggered by β-cell [Ca(2+)](c) is amplified by metabolic and receptor-generated signals. Diacylglycerol largely mediates acetylcholine (ACh) effects through protein-kinase C and other effectors, which can be directly activated by phorbol-ester (PMA). Using mouse islets, we investigated the possible role of microfilaments in ACh/PMA-mediated amplification of IS. PMA had no steady-state impact on actin microfilaments. Although ACh slightly augmented and PMA diminished glucose- and tolbutamide-induced increases in β-cell [Ca(2+)](c), both amplified IS in control islets and after microfilament disruption (latrunculin) or stabilization (jasplakinolide). Both phases of IS were larger in response to glucose than tolbutamide, although [Ca(2+)](c) was lower. This difference in secretion, which reflects metabolic amplification, persisted in presence of ACh/PMA and was independent of microfilaments. Amplification of IS by ACh/PMA is thus distinct from metabolic amplification, but both pathways promote acquisition of release competence by insulin granules, which can access exocytotic sites without intervention of microfilaments.
authors.affiliation: Unit of Endocrinology and Metabolism, University of Louvain, Faculty of Medicine, B-1200 Brussels, Belgium.
authors.forename: Nizar I
authors.initials: NI
authors.lastname: Mourad
authors.forename: Myriam
authors.initials: M
authors.lastname: Nenquin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Henquin
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010703:Phorbol Esters / Q000494:pharmacology*; D058105:Polymerization / Q000187:drug effects; D053778:Thiazolidines / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D047630:Depsipeptides; D007328:Insulin; D010703:Phorbol Esters; D053778:Thiazolidines; C057531:jasplakinolide; D014044:Tolbutamide; D005947:Glucose; D000109:Acetylcholine; C037067:latrunculin A; D002118:Calcium