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. 2009 Jun;22(2):133-7.
doi: 10.1293/tox.22.133. Epub 2009 Jul 7.

Segmentation of the Pathophysiological Stages of Diabetic Changes in the db/db Mouse

Masaki Yamazaki  1 , Atsuhiko Kato, Chie Kato, Etsuko Fujii, Kenji Adachi, Akio Miyoshi, Masami Suzuki
Affiliations

Segmentation of the Pathophysiological Stages of Diabetic Changes in the db/db Mouse

Masaki Yamazaki et al. J Toxicol Pathol. 2009 Jun.

Abstract

The db/db mouse is one of the diabetes mellitus animal models and if the pathophysiological stages of diabetic changes in the mouse model could simulate the stages in human diabetes, the db/db mouse could be used to better evaluate drug candidates. Blood insulin, HbA1c levels and morphological features of pancreatic islets in db/db mice were evaluated to determine the pathophysiological stage. At 6 weeks of age, db/db mice showed the highest level of plasma insulin and lowest level of HbA1c, and histopathological examination revealed enlarged islets with a circular shape and hypertrophic islet cells. By 9 and 12 weeks of age, the plasma insulin levels had decreased to mid levels and HbA1c had increased to mid to high levels; histopathological examination at this time revealed two types of islets coexisting, enlarged circular islets and small irregular-shaped islets. By 15 and 22 weeks of age, plasma insulin had decreased further to low levels and HbA1c was at its highest level; the histopathological examination at this time revealed an increase in irregular-shaped and small islets. Based on blood insulin levels, HbA1c levels and histopathology findings in the db/db mice in this study, the clinical staging of diabetic changes were recognized. The pathophysiological stages of diabetes mellitus in this animal model were similar to the stages in humans.

Keywords: HbA1c; db/db mouse; diabetes mellitus; histopathology; insulin; pancreas.

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Figures

Fig. 1.
Fig. 1.
Time course of changes of body weight (a), plasma insulin level (b) and HbA1c level (c) in the db/db mice. Each value represents the mean ± standard deviation.
Fig. 2.
Fig. 2.
The morphological features of pancreatic islets in db/db mice. Enlarged, circular islet at 6 weeks of age and islet cells with vacuoles (insert, × 600) (a), enlarged islet at 12 weeks of age (b), small irregular-shaped islet at 12 weeks of age (c) and a smaller and irregular-shaped islet at 22 weeks of age (d). Short arrows: large vacuoles considered to be Golgi apparatus. Long arrows: acinar cells, Arrowheads: spindle cells. Magnification: × 400. HE stain. Bar: 50 μm.
Fig. 3.
Fig. 3.
Pathophysiological stages of DM in humans and as represented in the db/db mouse. DM: Diabetes Mellitus. *The human column is quoted from reference .
See this image and copyright information in PMC

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