title: ATP enhances exocytosis of insulin secretory granules in pancreatic islets under Ca2+-depleted condition.
abstract: Glucose and other nutrients have been shown to stimulate insulin release from pancreatic islets under Ca2+-depleted condition when protein kinase A (PKA) and protein kinase C (PKC) are activated simultaneously. We investigated the role of metabolic nucleotide signals including ATP, ADP, and GTP in exocytosis of insulin secretory granules under Ca2+-depleted condition using electrically permeabilized rat islets. ATP under PKC activation augmented insulin release concentration-dependently by 100 nM 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in Ca2+-depleted condition, while ADP could not suppress ATP-dependent insulin release in this condition. Neither GTP nor activated PKA in the absence of PKC activation increased insulin release under Ca2+-depleted condition in the presence of ATP, but both enhanced insulin secretion in the presence of ATP when PKC was activated. In conclusion, activated PKC and the presence of ATP both are required in the insulin secretory process under Ca2+-depleted condition. While PKA activation and GTP cannot substitute for PKC activation and ATP, respectively, under Ca2+-depleted condition, they enhance ATP-dependent insulin secretion when PKC is activated.
authors.affiliation: Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Shimono
authors.forename: Shimpei
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Eri
authors.initials: E
authors.lastname: Mukai
authors.forename: Mihoko
authors.initials: M
authors.lastname: Takehiro
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nabe
authors.forename: Razvan Gheorghe
authors.initials: RG
authors.lastname: Radu
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimodahira
authors.forename: Rieko
authors.initials: R
authors.lastname: Kominato
authors.forename: Yo
authors.initials: Y
authors.lastname: Aramaki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nishi
authors.forename: Shogo
authors.initials: S
authors.lastname: Funakoshi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007328:Insulin; D000266:Adenylyl Imidodiphosphate; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium