title: A Spatial Model of Insulin-Granule Dynamics in Pancreatic β-Cells.
abstract: Insulin secretion from pancreatic β-cells in response to sudden glucose stimulation is biphasic. Prolonged secretion in vivo requires synthesis, delivery to the plasma membrane (PM) and exocytosis of insulin secretory granules (SGs). Here, we provide the first agent-based space-resolved model for SG dynamics in pancreatic β-cells. Using recent experimental data, we consider a single β-cell with identical SGs moving on a phenomenologically represented cytoskeleton network. A single exocytotic machinery mediates SG exocytosis on the PM. This novel model reproduces the measured spatial organization of SGs and insulin secretion patterns under different stimulation protocols. It proposes that the insulin potentiation effect and the rising second-phase secretion are mainly due to the increasing number of docking sites on the PM. Furthermore, it shows that 6 min after glucose stimulation, the 'newcomer' SGs are recruited from a region within less than 600 nm from the PM.
authors: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors: Jaber
authors: http://orcid.org/0000-0002-9719-8433
authors: J
authors: Dehghany
authors: Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.|German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
authors: Peter
authors: P
authors: Hoboth
authors: Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.|German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
authors: Anna
authors: A
authors: Ivanova
authors: Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.|German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
authors: Hassan
authors: H
authors: Mziaut
authors: Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.|German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
authors: Andreas
authors: A
authors: Müller
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.|Faculty of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia.
authors: Yannis
authors: Y
authors: Kalaidzidis
authors: Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.|German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.|Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors: Michele
authors: M
authors: Solimena
authors: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig, Germany.
authors: Michael
authors: M
authors: Meyer-Hermann
mesh_terms: D000818:Animals; D005089:Exocytosis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008954:Models, Biological; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: D007328:Insulin
keywords: agent-based model; biphasic insulin secretion; diabetes; granule dynamics; newcomer; potentiation; β-cell