Treatment with acarbose may improve endothelial dysfunction in streplozotocin-induced diabetic rats

We sought to determine whether a single reduction of hyperglycemia and thos e derivatives from nonenzymatic protein glycosylation may be effective in r educing the development of diabetic endothelial dysfunction. Therefore, we investigated how acarbose, an inhibitor of intestinal alpha-glucosidase tha t reduce hyperglycemia by lowering glucose absorption, may prevent the impa irment of acetylcholine (ACh)-induced endothelium-dependent relaxations obs erved in isolated vascular segments from untreated streptozotocin-induced d iabetic rats. When administered after diabetes induction, 10 mg/kg acarbose decreased modestly the enhancement of blood glucose and glycosylated hemog lobin (HbA(1c)) levels, but not those of advanced glycosylation end product s (AGEs). This effect was linked to a partial improvement of ACh-induced re sponses both in conductance vessels. such as aortic segments, and resistanc e vasculature, like mesenteric microvessels. When acarbose was introduced a fter 6 weeks of untreated diabetes, blood glucose, HbA(1c), and AGE levels were not affected and endothelial dysfunction remained unchanged in mesente ric microvessels, whereas a small improvement was observed in aortic segmen ts. The addition of 100 U/ml superoxide dismutase enhanced the impaired rel axations to values similar to vessels from nondiabetic rats, indicating a m ain role for superoxide anions in diabetes-induced endothelial dysfunction. We conclude that hyperglycemia itself or elevated HbA(1c), but not plasma AGEs, are related to enhanced oxidative stress and to the impairment of end othelium function associated to diabetes. This process can be partially pre vented by reducing glucose absorption with acarbose.