title: Integration of ATP, cAMP, and Ca2+ signals in insulin granule exocytosis.
abstract: Intracellular ATP, cAMP, and Ca2+ are major signals involved in the regulation of insulin secretion in the pancreatic beta-cell. We recently found that the ATP-sensitive K+ channel (KATP channel) as an ATP sensor, cAMP-GEFII as a cAMP sensor, Piccolo as a Ca2+ sensor, and L-type voltage-dependent Ca2+ channel (VDCC) can interact with each other. In the present study, we examined the effects of cAMP and ATP on the interaction of cAMP-GEFII and sulfonylurea receptor-1 (SUR1). Interaction of cAMP-GEFII with SUR1 was inhibited by the cAMP analog 8-bromo-cAMP but not by ATP, and the inhibition by 8-bromo-cAMP persisted in the presence of ATP. In addition, SUR1, cAMP-GEFII, and Piccolo could form a complex. Piccolo also interacted with the alpha1 1.2 subunit of VDCC in a Ca2+-independent manner. These data suggest that the interactions of the KATP channel, cAMP-GEFII, Piccolo, and L-type VDCC are regulated by intracellular signals such as cAMP and Ca2+ and that the ATP, cAMP, and Ca2+ signals are integrated at a specialized region of pancreatic beta-cells.
authors.affiliation: Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Shibasaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sunaga
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D007328:Insulin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP