|Troglitazone prevents and reverses dyslipidemia, insulin secretory defects, and histologic abnormalities in a rat model of naturally occurring obese diabetes.|
|PMID: 11016899 Owner: NLM Status: MEDLINE|
|Troglitazone has been shown to improve insulin sensitivity and thereby exert hypoglycemic effects in various animal models and humans with insulin resistance and diabetes. The recently established animal model of naturally occurring obese diabetes, the Otsuka Long-Evans Tokushima fatty (OLETF) rat, has many similarities with human type 2 diabetes mellitus and is characterized by a high degree of insulin resistance. In the present study, we examined the effect of pharmacologic intervention with troglitazone on metabolic and histopathologic changes in OLETF rats. Two groups of rats received a troglitazone-rich diet (200 mg/100 g normal chow) from age 12 weeks (ie, before the onset of diabetes) or 28 weeks (ie, after the onset of diabetes) to age 70 weeks, while a third group received standard rat chow. The addition of troglitazone to the diet did not alter food intake or body weight gain. Troglitazone had no influence on visceral adipose depots, but it significantly reduced fasting glucose, insulin, cholesterol, triglyceride (TG), and free fatty acid (FFA) levels. Troglitazone reduced the insulin resistance and maintained the postglycemic insulin response at a normal level, and thus inhibited the development of insulin insensitivity and frank diabetes in OLETF rats up to 70 weeks of age. The pancreatic wet weight and insulin content were significantly higher in the treated rat groups versus the control rats. The morphologic changes observed in the control rats, such as fibrosis and structural disarrangement of islets, were minimal in the troglitazone-treated rats. Our study demonstrates that troglitazone, albeit at a dosage 10 to 15 times higher than that in humans, not only prevents but also reverses the metabolic derangement and histopathologic changes in genetically determined obese diabetes.|
|D M Jia; A Tabaru; H Nakamura; K I Fukumitsu; T Akiyama; M Otsuki|
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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: Metabolism: clinical and experimental Volume: 49 ISSN: 0026-0495 ISO Abbreviation: Metab. Clin. Exp. Publication Date: 2000 Sep|
|Created Date: 2000-10-12 Completed Date: 2000-10-12 Revised Date: 2006-11-15|
Medline Journal Info:
|Nlm Unique ID: 0375267 Medline TA: Metabolism Country: UNITED STATES|
|Languages: eng Pagination: 1167-75 Citation Subset: IM|
|Third Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.|
|APA/MLA Format Download EndNote Download BibTex|
Blood Glucose / analysis
Cholesterol / blood
Chromans / therapeutic use*
Diabetes Mellitus / drug therapy*, pathology, physiopathology
Diabetes Mellitus, Type 2 / drug therapy, pathology, physiopathology
Fatty Acids, Nonesterified / blood
Glucose Tolerance Test
Hyperlipidemias / drug therapy, prevention & control*
Hypoglycemic Agents / therapeutic use*
Insulin / analysis, blood, secretion*
Pancreas / chemistry, pathology
Rats, Inbred Strains
Thiazoles / therapeutic use*
Triglycerides / blood
|0/Blood Glucose; 0/Chromans; 0/Fatty Acids, Nonesterified; 0/Hypoglycemic Agents; 0/Thiazoles; 0/Thiazolidinediones; 0/Triglycerides; 11061-68-0/Insulin; 57-88-5/Cholesterol; 97322-87-7/troglitazone|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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