title: New horizons in cellular regulation by inositol polyphosphates: insights from the pancreatic β-cell.
abstract: Studies of inositol polyphosphates in the pancreatic β-cell have led to an exciting synergism between new discoveries regarding their cellular roles and new insights into β-cell function. Because the loss or malfunction of the β-cell is central to diabetes, these studies open the possibility of new pharmacological interventions in a disease that has reached epidemic proportions worldwide. Using the β-cell as our prime but not exclusive example, we examine the inositol polyphosphates in three main groups: 1) inositol 1,4,5-trisphosphate and its influence on Ca(2+) signaling, specifically in a cell in which cytoplasmic-free Ca(2+) concentration is principally increased by plasma membrane standing voltage-gated Ca(2+) channels; 2) higher inositol polyphosphates including a novel second messenger inositol 3,4,5,6-tetrakisphosphate and a regulatory role for inositol hexakisphosphate in β-cell Ca(2+) homeostasis and exo- and endocytosis; and 3) inositol pyrophosphates and their role in β-cell exocytosis, together with the exciting possibility of being novel targets for therapy in diabetes. We conclude with some of the new perspectives that are likely to become apparent in the next few years.
authors: The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76 Stockholm, Sweden.
authors: Christopher J
authors: CJ
authors: Barker
authors: Per-Olof
authors: PO
authors: Berggren
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000737:chemistry / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D007295:Inositol Phosphates / Q000737:chemistry / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D010833:Phytic Acid / Q000737:chemistry / Q000502:physiology
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D007328:Insulin; C081652:inositol-3,4,5,6-tetrakisphosphate; D010833:Phytic Acid; D015544:Inositol 1,4,5-Trisphosphate; D005947:Glucose; D002118:Calcium