title: Osteopontin Affects Insulin Vesicle Localization and Ca2+ Homeostasis in Pancreatic Beta Cells from Female Mice.
abstract: Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN-/-). Ultra-structural analyzes of islets from OPN-/- and WT mice indicated weaker cell-cell connections between the islet cells in the OPN-/- mouse compared to WT. Analysis of the insulin granule distribution in the beta cells showed that although OPN-/- and WT beta cells have the same number of insulin granules OPN-/- beta cells have significantly fewer docked granules. Both OPN-/- and WT islets displayed synchronized Ca2+ oscillations indicative of an intact beta cell communication. OPN-/- islets displayed higher intracellular Ca2+ concentrations when stimulated with 16.7 mM glucose than WT islets and the initial dip upon elevated glucose concentrations (which is associated with Ca2+ uptake into ER) was significantly lower in these islets. Glucose-induced insulin secretion was similar in OPN-/- and WT islets. Likewise, non-fasted blood glucose levels were the same in both groups. In summary, deletion of OPN results in several minor beta-cell defects that can be compensated for in a healthy system.
authors.affiliation: Unit of Islet Cell Exocytosis, Lund University Diabetes Centre, Department of Clinical Sciences in Malmö, Lund University, Clinical Research Centre, Malmö, Sweden.
authors.forename: Anna
authors.identifier: http://orcid.org/0000-0001-8807-5979
authors.initials: A
authors.lastname: Wendt
authors.affiliation: Unit of Islet Cell Exocytosis, Lund University Diabetes Centre, Department of Clinical Sciences in Malmö, Lund University, Clinical Research Centre, Malmö, Sweden.
authors.forename: Inês G
authors.initials: IG
authors.lastname: Mollet
authors.affiliation: Vessel Wall Biology, Department of Experimental Medical Science, Lund University, Biomedical Center, Lund, Sweden.
authors.forename: Anki
authors.initials: A
authors.lastname: Knutsson
authors.affiliation: Vessel Wall Biology, Department of Experimental Medical Science, Lund University, Biomedical Center, Lund, Sweden.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Bolmgren
authors.affiliation: Vessel Wall Biology, Department of Experimental Medical Science, Lund University, Biomedical Center, Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Hultgårdh-Nilsson
authors.affiliation: Unit of Vascular excitation-transcription (ET) coupling, Lund University Diabetes Centre, Department of Clinical Sciences in Malmö, Lund University, Clinical Research Centre, Malmö, Sweden.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Gomez
authors.affiliation: Unit of Islet Cell Exocytosis, Lund University Diabetes Centre, Department of Clinical Sciences in Malmö, Lund University, Clinical Research Centre, Malmö, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Eliasson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology* / Q000648:ultrastructure; D007444:Inulin / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D053495:Osteopontin / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D022142:Secretory Vesicles / Q000502:physiology / Q000648:ultrastructure
chemical_list: D053495:Osteopontin; D007444:Inulin; D002118:Calcium