Effects of Troglitazone on Collagen Accumulation and Distensibility of Aortic Wall in Prestage of Non-Insulin-Dependent Diabetes Mellitus of Otsuka Long-Evans Tokushima Fatty Rats

Abstract

We investigated the effect of troglitazone (TG) on aortic distensibility and histopathology at the preclinical stage in the non-insulin-dependent diabetes mellitus (NIDDM) model. Twenty male diabetic and 20 male nondiabetic rats were each divided into two groups: treated-DM, untreated-DM, treated-nonDM, and untreated-nonDM. TG (0.2%) was mixed in chow in the treated groups. From age 5 to 15 weeks, fast blood glucose and insulin were monitored. At 15 weeks, oral glucose tolerance test results, aortic wall histopathology, and collagen content were studied, and intravascular ultrasound images and aortic pressure were recorded. Aortic diameter was measured during the cardiac cycle, and the stiffness parameter beta was calculated. Blood glucose (mg/dl) 2 h after loading in treated-DM (139+/-20) was normalized (untreated-DM, 188+/-27; p<0.05). Insulin concentration (ng/ml) in treated-DM (3.2+/-0.4) was lower than that in untreated-DM (8.1+/-1.5; p<0.01). At 15 weeks, beta in untreated-DM (2.4+/-0.8) was larger than those in untreated-nonDM (1.5+/-0.4; p<0.0001) and in treated-DM (1.9+/-0.4, p = 0.0081). Aortic wall collagen (mg/g dry weight) increased in untreated-DM (32.8+/-3.3) as compared with treated-DM (28.1+/-3.8; p = 0.048). Histomorphometry showed decreased medial area (mm2) in treated-DM (0.55+/-0.05) compared with untreated-DM (0.78+/-0.12; p<0.0001). This study suggests that TG may prevent metabolic abnormalities and the deterioration of aortic distensibility at an early prediabetic stage.