A novel mouse model for type 2 diabetes and non-alcoholic fatty liver disease: spontaneous amelioration of diabetes by augmented beta cell mass.
Given the potential for beta-cells to increase their mass, glucose intolerance might be ameliorated by a compensatory increase in beta-cell mass. However, it remains uncertain whether such amelioration is feasible in vivo. In this study, we investigated glucose tolerance, islet morphology, and islet gene expression of Fatty Liver Shionogi (FLS) mice, a model for non-alcoholic fatty liver disease (NAFLD). Relative to control mice, FLS mice showed an age-dependent increase in glucose intolerance up to the age of 24 weeks, leading to the development of diabetes. After this time, glucose tolerance ameliorated spontaneously and diabetes resolved by 48 week of age, associated with marked hyperinsulinemia. Islets of the FLS mice demonstrated a marked increase in beta-cell mass with an increase in beta-cell numbers. Islet gene expression analysis in FLS mice demonstrated no changes in gene expression of glucokinase or insulin receptor substrate 2. These data demonstrated that the 24-week-old FLS mouse is a model for type 2 diabetes with NAFLD and that the 48-week-old FLS mouse exhibits spontaneous amelioration of type 2 diabetes associated with augmented beta-cell number/mass.
Oze-Fukai
Aya
A
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Fujisawa
Tomomi
T
Sugimoto
Ken
K
Nojima
Koji
K
Shindo
Nobuyasu
N
Shimoyoshi
Satomi
S
Yoshikawa
Yuki
Y
Sato
Yoshifumi
Y
Shimomura
Iichirou
I
Ikegami
Hiroshi
H
Rakugi
Hiromi
H
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics*; D005941:Glucokinase / Q000235:genetics; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse; D005941:Glucokinase