Intra-islet lesions and lobular variations in β-cell mass expansion in ob/ob mice revealed by 3D imaging of intact pancreas

Sci Rep. 2016 Oct 7:6:34885. doi: 10.1038/srep34885.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fibrin / metabolism
  • Hypertrophy
  • Imaging, Three-Dimensional
  • Islets of Langerhans / diagnostic imaging*
  • Islets of Langerhans / pathology*
  • Mice, Obese
  • Pancreas / cytology
  • Pancreas / diagnostic imaging*
  • Pancreas / pathology
  • Tomography, Optical / methods

Substances

  • Fibrin