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

Saba Parween,Maria Eriksson,Ulf Ahlgren,Per Lindström,Christoffer Nord,Elena Kostromina

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.

Highlights

The pancreas is a mixed endocrine and exocrine gland that plays a pivotal role in maintaining blood glucose homeostasis
In this study we used optical projection tomography (OPT) imaging to describe the development of islet hypertrophy in the ob/ob mouse between 4 and 52 weeks of age
Using state of the art techniques for OPT and UM imaging, we provide detailed 3D and quantitative data regarding the BCV expansion in isolated pancreata from ob/obumeå and lean control mice

Summary

Introduction

The pancreas is a mixed endocrine and exocrine gland that plays a pivotal role in maintaining blood glucose homeostasis. Another study, using bioluminescence imaging (BLI) to monitor BCM in ob/ob mice in vivo, incorporated an extensive stereological β-cell quantification of the model[7] These and other studies provided important information on the BCM dynamics of ob/ob mice, they depend on the extrapolation of two-dimensional data (as do all stereological approaches) or, as in the case of BLI, provide only diminutive spatial information. Whereas it has been demonstrated in other models for insulin resistance that β-cell adaptation could be topologically heterogeneous[8], no information of this kind exists for the ob/ob model. We provide detailed statistics on BCM expansion (to better adhere with the principle of detection: β-cell volume (BCV) will be used throughout) and its topological distribution, as well as a putative mechanism for the formation of a cystic aberration forming in hyperplastic ob/ob islets

Methods

Results

Conclusion