title: Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat.
abstract: We recently established a novel animal model of obese type 2 diabetes (T2D), the Zucker fatty diabetes mellitus (ZFDM) rat strain harboring the fatty mutation (fa) in the leptin receptor gene. Here we performed a phenotypic characterization of the strain, focusing mainly on the prediabetic state. At 6-8 weeks of age, fa/fa male rats exhibited mild glucose intolerance and severe insulin resistance. Although basal insulin secretion was remarkably high in the isolated pancreatic islets, the responses to both glucose stimulation and the incretin GLP-1 were retained. At 10-12 weeks of age, fa/fa male rats exhibited marked glucose intolerance as well as severe insulin resistance similar to that at the earlier age. In the pancreatic islets, the insulin secretory response to glucose stimulation was maintained but the response to the incretin was diminished. In nondiabetic Zucker fatty (ZF) rats, the insulin secretory responses to both glucose stimulation and the incretin in the pancreatic islets were similar to those of ZFDM rats. As islet architecture was destroyed with age in ZFDM rats, a combination of severe insulin resistance, diminished insulin secretory response to incretin, and intrinsic fragility of the islets may cause the development of T2D in this strain.
authors.affiliation: Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Ghupurjan
authors.initials: G
authors.lastname: Gheni
authors.affiliation: Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Norihide
authors.identifier: 0000-0002-5596-9754
authors.initials: N
authors.lastname: Yokoi
authors.affiliation: Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan ; Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Beppu
authors.affiliation: Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan ; Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Shihomi
authors.initials: S
authors.lastname: Hidaka
authors.affiliation: Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kawabata
authors.affiliation: Hoshino Laboratory Animals, Inc., Ibaraki 306-0606, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hoshino
authors.affiliation: Hoshino Laboratory Animals, Inc., Ibaraki 306-0606, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hoshino
authors.affiliation: Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D018149:Glucose Intolerance / Q000235:genetics / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D011236:Prediabetic State / Q000235:genetics / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D054411:Receptors, Leptin / Q000235:genetics
chemical_list: D007328:Insulin; D054411:Receptors, Leptin