Arteriolar anatomical and functional abnormalities in juvenile mice with genetic or streptozotocin-induced diabetes mellitus.

Abstract

The hypothesis that a state of hyperglycemia in hyper- and hypoinsulinemic animal models of diabetes mellitus is associated with arteriolar pathology was tested. Hyperglycemic, hyperinsulinemic obese mice and Jackson diabetic mice at age 8 wk were used as hyperglycemic, hyperinsulinemic models; and normal mice, treated with streptozotocin (100 mg/kg) at age 4 wk and studied at age 8 and 16 wk, served as hyperglycemic, hypoinsulinemic models. All mice were anesthetized lightly, and the microvasculature of the cremaster muscle was observed in vivo. The inner diameters of the large arterioles in diabetic mice are significantly (P < 0.05) smaller than normal, yet the smallest arterioles in diabetic mice have significantly (P < 0.05) increased inner diameters. The cross-sectional areas of the vessel walls for large and intermediate diameter arterioles are significantly (P < 0.05) decreased by up to 50% in diabetic mice. The smallest arterioles have an increased wall area but have a poorly developed coat of vascular smooth muscle cells. The number of arterioles open to blood flow is significantly (P < 0.05) decreased by 20-50% in all diabetic mice in the intact and passive (sodium nitroprusside suffusion, 1 mg/ml) state. The dilation of the majority of arterioles from the intact to passive state is significantly (P < 0.05) less than normal in diabetics. A common arteriolar pathology in hyperglycemic mice that are either hyper- or hypoinsulinemic is indicated. The decreased number of arterioles and the failure of arterioles to dilate properly is due to abnormal development of the vessel wall in juvenile diabetic mice.