title: Segmentation of the Pathophysiological Stages of Diabetic Changes in the db/db Mouse.
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.
authors.affiliation: Safety Assessment Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kato
authors.forename: Chie
authors.initials: C
authors.lastname: Kato
authors.forename: Etsuko
authors.initials: E
authors.lastname: Fujii
authors.forename: Kenji
authors.initials: K
authors.lastname: Adachi
authors.forename: Akio
authors.initials: A
authors.lastname: Miyoshi
authors.forename: Masami
authors.initials: M
authors.lastname: Suzuki