title: A novel mouse model for type 2 diabetes and non-alcoholic fatty liver disease: spontaneous amelioration of diabetes by augmented beta cell mass.
abstract: 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.
authors.affiliation: Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Oze-Fukai
authors.forename: Tomomi
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Koji
authors.initials: K
authors.lastname: Nojima
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Shindo
authors.forename: Satomi
authors.initials: S
authors.lastname: Shimoyoshi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Iichirou
authors.initials: I
authors.lastname: Shimomura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse; D005941:Glucokinase