title: Characterization of STZ-Induced Type 2 Diabetes in Zucker Fatty Rats.
abstract: The Zucker fatty (ZF) rat is a disease model of obesity and metabolic syndrome, such as hyperlipidemia and insulin resistance, resulting from hyperphagia owing to the loss of function of the leptin receptor, but it rarely develops hyperglycemia. We examined the effects of different doses of streptozotocin (STZ). A low dosage of STZ (30 mg/kg body weight, i.p.) elevated blood glucose levels in ZF rats up to 300 mg/dl within a week, and to nearly 500 mg/dl by 5 weeks after injection of STZ. Besides hyperglycemia, STZ-treated ZF (STZ-ZF) rats retained metabolic syndrome features such as hyperlipidemia and hyperinsulinemia. The stimulated insulin secretion in response to orally-loaded glucose disappeared completely in STZ-ZF rats. Although there were no significant differences in the morphology of pancreatic islets between vehicle-treated ZF (Cont-ZF) and STZ-ZF rats, the insulin content was markedly decreased in STZ-ZF rats. The hepatic gene expression for gluconeogenic enzymes was upregulated in STZ-ZF rats compared with Cont-ZF rats. Metformin lowered the blood glucose levels of STZ-ZF rats in a dose-dependent manner. These results suggest that STZ-ZF rats are useful for studies of T2DM and for the evaluation of the efficacy of anti-diabetic drugs.
authors.affiliation: First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamoto
authors.forename: Naohide
authors.initials: N
authors.lastname: Kanemoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ohbuchi
authors.forename: Mai
authors.initials: M
authors.lastname: Okano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukui
authors.forename: Toshiki
authors.initials: T
authors.lastname: Sudo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006442:Glycated Hemoglobin / Q000032:analysis; D006943:Hyperglycemia / Q000150:complications; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced; D051381:Rats; D011924:Rats, Zucker; D013311:Streptozocin / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D008055:Lipids; D013311:Streptozocin