Cardioprotective effects of troglitazone in streptozotocin-induced diabetic rats.
Troglitazone, a new oral antidiabetic agent, shows hypoglycemic effects in insulin-resistant animal models and humans. This study was conducted to evaluate the effects of troglitazone on the heart of diabetic animals. Streptozotocin (STZ)-induced diabetic rats and age-matched controls were treated with troglitazone as a 0.2% food admixture for 6 weeks. Basal and postischemic cardiac functions at 14 weeks of age were then examined in isolated working heart. Troglitazone treatment did not attenuate the insulinopenia and hyperglycemia of diabetic rats, but it partially improved the hypertriglyceridemia. Troglitazone treatment partially restored the basal heart rate and cardiac work of diabetic rats to nearly control values. Troglitazone also improved the postischemic functional deficits of diabetic rats: heart rate (untreated 61% of baseline at 30-minute reperfusion v treated 92%, P < .001), left ventricular (LV) developed pressure (54% v 94%, P < .001), peak positive ([LV + dP/dt] 54% v 93%, P < .001) and negative ([LV -dP/dt] 53% v 94%, P < .001) first derivative of LV, and cardiac work (44% v 98%, P < .001). Diabetic animals showed ultrastructural damage including disarray of sarcomere, disorganization of mitochondrial matrix, cytoplasmic vacuolization, and invagination of nuclear membrane; these were partially normalized by troglitazone treatment. Our results suggest that troglitazone treatment has a cardiprotective effect on the basal and postischemic cardiac function of STZ-induced diabetic rats.
Shimabukuro
M
M
Second Department of Internal Medicine, Faculty of Medicine, University of The Ryukyus, Okinawa, Japan.
Higa
S
S
Shinzato
T
T
Nagamine
F
F
Komiya
I
I
Takasu
N
N
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D002839:Chromans / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006334:Heart Function Tests; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008854:Microscopy, Electron; D017202:Myocardial Ischemia / Q000503:physiopathology; D009206:Myocardium / Q000648:ultrastructure; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D045162:Thiazolidinediones; D014280:Triglycerides / Q000097:blood; D000077288:Troglitazone
D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; D002784:Cholesterol; D000077288:Troglitazone