Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, United States; Department for Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, United States; Department for Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
Catherine A Doyle
Department of Pharmacology, University of Virginia, Charlottesville, United States
Noah Schenk
Department of Pharmacology, University of Michigan, Ann Arbor, United States
Clint M Upchurch
Department of Pharmacology, University of Virginia, Charlottesville, United States
Margaret Elmer-Dixon
Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, United States; Department for Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
Amanda E Ward
Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, United States; Department for Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
Julia Preobraschenski
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany; Cluster of Excellence in Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells and Institute for Auditory Neuroscience, University of Göttingen, Göttingen, Germany
Syed S Hussein
Department of Microbiology, University of Virginia, Charlottesville, United States
Weronika Tomaka
Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, United States; Department for Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
Patrick Seelheim
Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, United States; Department for Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
Iman Kattan
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
Megan Harris
Department of Cell Biology, University of Virginia, Charlottesville, United States
Binyong Liang
Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, United States; Department for Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
Anne K Kenworthy
Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, United States; Department for Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, United States; Department of Pharmacology, University of Virginia, Charlottesville, United States
Norbert Leitinger
Department of Pharmacology, University of Virginia, Charlottesville, United States
Arun Anantharam
Department of Pharmacology, University of Michigan, Ann Arbor, United States
Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, United States; Department of Cell Biology, University of Virginia, Charlottesville, United States
Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, United States; Department for Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
Insulin secretion from β-cells is reduced at the onset of type-1 and during type-2 diabetes. Although inflammation and metabolic dysfunction of β-cells elicit secretory defects associated with type-1 or type-2 diabetes, accompanying changes to insulin granules have not been established. To address this, we performed detailed functional analyses of insulin granules purified from cells subjected to model treatments that mimic type-1 and type-2 diabetic conditions and discovered striking shifts in calcium affinities and fusion characteristics. We show that this behavior is correlated with two subpopulations of insulin granules whose relative abundance is differentially shifted depending on diabetic model condition. The two types of granules have different release characteristics, distinct lipid and protein compositions, and package different secretory contents alongside insulin. This complexity of β-cell secretory physiology establishes a direct link between granule subpopulation and type of diabetes and leads to a revised model of secretory changes in the diabetogenic process.
