Troglitazone prevents fatty changes of the liver in obese diabetic rats.
OBJECTIVE
Troglitazone is a newly developed antidiabetic drug and is indicated to be useful for the treatment of patients with type II diabetes mellitus. Recently, however, it became clear that troglitazone could cause liver dysfunction in some patients. In addition, a relationship between the activation of the peroxisome proliferator-activated receptor gamma receptor by troglitazone and colon tumorigenesis has been suggested. The present study was undertaken to examine the effects of long-term administration of troglitazone on the liver and intestine in genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) and control Long-Evans Tokushima Otsuka (LETO) rats.


METHODS
A troglitazone-rich diet (200 mg/100 g normal chow) or a standard rat chow, free of troglitazone (control), was given to OLETF and LETO rats from 12 or 28 weeks of age until 72 weeks of age. Serum levels of glucose, insulin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined at several time points. In addition, histology of the liver and intestine and serum levels of cholesterol and triglycerides were examined at 72 weeks of age.


RESULTS
Troglitazone prevented age-related increases in fasting glucose and insulin concentrations in OLETF rats, but had no significant influences on serum levels of AST and ALT in both strains of rats. The liver weights in the control OLETF rats were significantly heavier than in the LETO rats. Troglitazone significantly reduced serum cholesterol and triglyceride levels and the liver weight. However, it had no influence on the large intestine weight and the number of colonic polyps in both OLETF and LETO rats. Sections of the liver from the untreated OLETF rats showed mild fatty changes in the central zone of the hepatic lobule, whereas those from the troglitazone-treated OLETF rats appeared normal with no fat deposition in the hepatocytes. Troglitazone in LETO rats also caused no significant histopathologic changes of the liver tissue.


CONCLUSIONS
Our present study demonstrated that long-term administration of troglitazone prevents the progress of the metabolic derangement and fatty changes of the liver in genetically determined obese diabetes.
Jia
D M
DM
Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu, Japan.
Tabaru
A
A
Akiyama
T
T
Abe
S
S
Otsuki
M
M
D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D002839:Chromans / Q000008:administration & dosage* / Q000009:adverse effects; D003106:Colon / Q000033:anatomy & histology; D003111:Colonic Polyps / Q000473:pathology; D003627:Data Interpretation, Statistical; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000517:prevention & control*; D006949:Hyperlipidemias / Q000097:blood; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000097:blood; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D045162:Thiazolidinediones; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D000077288:Troglitazone
D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077288:Troglitazone