title: Inhibition of phosphatases and increased Ca2+ channel activity by inositol hexakisphosphate.
abstract: Inositol hexakisphosphate (InsP6), the dominant inositol phosphate in insulin-secreting pancreatic beta cells, inhibited the serine-threonine protein phosphatases type 1, type 2A, and type 3 in a concentration-dependent manner. The activity of voltage-gated L-type calcium channels is increased in cells treated with inhibitors of serine-threonine protein phosphatases. Thus, the increased calcium channel activity obtained in the presence of InsP6 might result from the inhibition of phosphatase activity. Glucose elicited a transient increase in InsP6 concentration, which indicates that this inositol polyphosphate may modulate calcium influx over the plasma membrane and serve as a signal in the pancreatic beta cell stimulus-secretion coupling.
authors.affiliation: Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, S-171 76 Stockholm, Sweden.
authors.forename: O
authors.initials: O
authors.lastname: Larsson
authors.forename: C J
authors.initials: CJ
authors.lastname: Barker
authors.forename: A
authors.initials: A
authors.lastname: Sjöholm
authors.forename: H
authors.initials: H
authors.lastname: Carlqvist
authors.forename: R H
authors.initials: RH
authors.lastname: Michell
authors.forename: A
authors.initials: A
authors.lastname: Bertorello
authors.forename: T
authors.initials: T
authors.lastname: Nilsson
authors.forename: R E
authors.initials: RE
authors.lastname: Honkanen
authors.forename: G W
authors.initials: GW
authors.lastname: Mayr
authors.forename: J
authors.initials: J
authors.lastname: Zwiller
authors.forename: P O
authors.initials: PO
authors.lastname: Berggren
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D007294:Inositol / Q000494:pharmacology; D007295:Inositol Phosphates / Q000494:pharmacology; D015640:Ion Channel Gating; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010833:Phytic Acid / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D015220:Calcium Channels; D007295:Inositol Phosphates; D007294:Inositol; D010833:Phytic Acid; D010749:Phosphoprotein Phosphatases; D005947:Glucose; D002118:Calcium