Linagliptin treatment improves cerebrovascular function and remodeling and restores reduced cerebral perfusion in Type 2 diabetes

In this study, we hypothesized that DPP-IV inhibition with linagliptin would improve impaired cerebral perfusion in diabetic rats, as well as improve insulin-induced cerebrovascular relaxation and reverse pathological cerebrovascular remodeling. We further postulated that these changes would lead to a subsequent improvement of cognitive function. Male Type-2 diabetic and nondiabetic Goto-Kakizaki rats were treated with linagliptin for 4 wk, and blood glucose and DPP-IV plasma levels were assessed. Cerebral perfusion was assessed after treatment using laser-Doppler imaging, and dose response to insulin (10–13 M–10–6 M) in middle cerebral arteries was tested on a pressurized arteriograph. The impact of DPP-IV inhibition on diabetic cerebrovascular remodeling was assessed over a physiologically relevant pressure range, and changes in short-term hippocampus-dependent learning were observed using a novel object recognition test. Linagliptin lowered DPP-IV activity but did not change blood glucose or insulin levels in diabetes. Insulin-mediated vascular relaxation and cerebral perfusion were improved in the diabetic rats with linagliptin treatment. Indices of diabetic vascular remodeling, such as increased cross-sectional area, media thickness, and wall-to-lumen ratio, were also ameliorated; however, improvements in short-term hippocampal-dependent learning were not observed. The present study provides evidence that linagliptin treatment improves cerebrovascular d...
Source: AJP: Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Obesity, Diabetes and Energy Homeostasis Source Type: research