28 Week‐old Type‐2 Diabetic Goto‐Kakizaki Rats Exhibit a Reduction to Insulin‐Mediated Vasorelaxation in Middle Cerebral Arteries

Abstract

We have previously shown in our lab that type-2 diabetic Goto-Kakizaki (GK) rats develop cerebrovascular endothelial dysfunction. It has been reported that insulin mediated relaxation in middle cerebral arteries (MCA) is dependent on endothelium. Therefore, we hypothesized that diabetic GK rats would exhibit impaired MCA vasorelaxation to insulin. MCAs from 28 week-old diabetic (Hemoglobin A1C >6.5%) and non-diabetic GK rats were mounted on an arteriograph and experiments were performed at 60mmHg. The vessels were pre-constricted with 1 µM serotonin to achieve at least 30% reduction in lumen diameter, and relaxation response to insulin (10-13- 10-6 M) was observed. Maximal relaxation response (Rmax) was observed as % relaxation of lumen diameter. Diabetic rats exhibited a decrease in response to insulin relaxation compared to non-diabetic vehicle rats (Rmax: 18.5± 4.32 vs. 57.7± 8.16, p蠄 0.05). Additionally, we measured the response to acetylcholine (ACh) stimulus (1 µM) in basilar arteries pre-constricted with 1 µM serotonin on a tension myograph. We did not observe a significant difference between the diabetic and non-diabetic groups (Rmax as % reduction from maximal serotonin response: 29.9± 9.08 vs. 18.1± 2.65, p> 0.05). This reduction in response to ACh demonstrates an age-dependent deterioration in basilar endothelial function compared to our labs previous work in younger rats. These results demonstrate that aged diabetic GK rats have a significant reduction in cerebrovascular endothelial function, where both the age of the animal as well as the presence of hyperglycemia are contributing to this decline.