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@ARTICLE{Fava:141200,
      author       = {Fava, E. and Dehghany, J. and Ouwendijk, J. and Müller, A.
                      and Niederlein, A. and Verkade, P. and Meyer-Hermann, M. and
                      Solimena, M.},
      title        = {{N}ovel standards in the measurement of rat insulin
                      granules combining electron microscopy, high-content image
                      analysis and in silico modelling.},
      journal      = {Diabetologia},
      volume       = {55},
      number       = {4},
      issn         = {0012-186X},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DZNE-2020-07522},
      pages        = {1013-1023},
      year         = {2012},
      abstract     = {Knowledge of number, size and content of insulin secretory
                      granules is pivotal for understanding the physiology of
                      pancreatic beta cells. Here we re-evaluated key structural
                      features of rat beta cells, including insulin granule size,
                      number and distribution as well as cell size.Electron
                      micrographs of rat beta cells fixed either chemically or by
                      high-pressure freezing were compared using a high-content
                      analysis approach. These data were used to develop
                      three-dimensional in silico beta cell models, the slicing of
                      which would reproduce the experimental datasets.As
                      previously reported, chemically fixed insulin secretory
                      granules appeared as hollow spheres with a mean diameter of
                      ∼350 nm. Remarkably, most granules fixed by high-pressure
                      freezing lacked the characteristic halo between the dense
                      core and the limiting membrane and were smaller than their
                      chemically fixed counterparts. Based on our analyses, we
                      conclude that the mean diameter of rat insulin secretory
                      granules is 243 nm, corresponding to a surface area of
                      0.19 μm(2). Rat beta cells have a mean volume of
                      763 μm(3) and contain 5,000-6,000 granules.A major reason
                      for the lower mean granule number/rat beta cell relative to
                      previous accounts is a reduced estimation of the mean beta
                      cell volume. These findings imply that each granule contains
                      about twofold more insulin, while its exocytosis increases
                      membrane capacitance about twofold less than assumed
                      previously. Our integrated approach defines new standards
                      for quantitative image analysis of beta cells and could be
                      applied to other cellular systems.},
      keywords     = {Animals / Cells, Cultured / Cytoplasmic Granules:
                      metabolism / Cytoplasmic Granules: ultrastructure / Female /
                      Insulin: metabolism / Insulin-Secreting Cells: metabolism /
                      Insulin-Secreting Cells: ultrastructure / Microscopy,
                      Electron, Transmission / Rats / Rats, Wistar / Secretory
                      Vesicles: metabolism / Secretory Vesicles: ultrastructure /
                      Insulin (NLM Chemicals)},
      cin          = {AG Fava 1},
      ddc          = {610},
      cid          = {I:(DE-2719)1013016},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:22252472},
      pmc          = {pmc:PMC3296007},
      doi          = {10.1007/s00125-011-2438-4},
      url          = {https://pub.dzne.de/record/141200},
}