title: Intra-islet lesions and lobular variations in β-cell mass expansion in ob/ob mice revealed by 3D imaging of intact pancreas.
abstract: The leptin deficient ob/ob mouse is a widely used model for studies on initial aspects of metabolic disturbances leading to type 2 diabetes, including insulin resistance and obesity. Although it is generally accepted that ob/ob mice display a dramatic increase in β-cell mass to compensate for increased insulin demand, the spatial and quantitative dynamics of β-cell mass distribution in this model has not been assessed by modern optical 3D imaging techniques. We applied optical projection tomography and ultramicroscopy imaging to extract information about individual islet β-cell volumes throughout the volume of ob/ob pancreas between 4 and 52 weeks of age. Our data show that cystic lesions constitute a significant volume of the hyperplastic ob/ob islets. We propose that these lesions are formed by a mechanism involving extravasation of red blood cells/plasma due to increased islet vessel blood flow and vessel instability. Further, our data indicate that the primary lobular compartments of the ob/ob pancreas have different potentials for expanding their β-cell population. Unawareness of the characteristics of β-cell expansion in ob/ob mice presented in this report may significantly influence ex vivo and in vivo assessments of this model in studies of β-cell adaptation and function.
authors.affiliation: Umeå Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
authors.forename: Saba
authors.initials: S
authors.lastname: Parween
authors.affiliation: Umeå Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
authors.forename: Elena
authors.initials: E
authors.lastname: Kostromina
authors.affiliation: Umeå Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Nord
authors.affiliation: Umeå Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Eriksson
authors.affiliation: Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Lindström
authors.affiliation: Umeå Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Ahlgren
mesh_terms: D000818:Animals; D005337:Fibrin / Q000378:metabolism; D006984:Hypertrophy; D021621:Imaging, Three-Dimensional; D007515:Islets of Langerhans / Q000000981:diagnostic imaging* / Q000473:pathology*; D008820:Mice, Obese; D010179:Pancreas / Q000166:cytology / Q000000981:diagnostic imaging* / Q000473:pathology; D041622:Tomography, Optical / Q000379:methods
chemical_list: D005337:Fibrin