Intra-islet lesions and lobular variations in ?-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 ?-cell mass to compensate for increased insulin demand, the spatial and quantitative dynamics of ?-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 ?-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 ?-cell population. Unawareness of the characteristics of ?-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 ?-cell adaptation and function.

SUBMITTER: Parween S 

PROVIDER: S-EPMC5054357 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature