Knockout of AKAP150 improves impaired BK channel‐mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus

Vascular dysfunction resulting from diabetes is an important factor in arteriosclerosis. Previous studies have shown that during hyperglycaemia and diabetes, AKAP150 promotes vascular tone enhancement by intensifying the remodelling of the BK channel. However, the interaction between AKAP150 and the BK channel remains open to discussion. In this study, we investigated the regulation of impaired BK channel-mediated vascular dysfunction in diabetes mellitus. Using AKAP150 null mice (AKAP150(-/-) ) and wild-type (WT) control mice (C57BL/6J), diabetes was induced by intraperitoneal injection of streptozotocin. We found that knockout of AKAP150 reversed vascular remodelling and fibrosis in mice with diabetes and in AKAP150(-/-) diabetic mice. Impaired Akt/GSK3beta signalling contributed to decreased BK-beta1 expression in aortas from diabetic mice, and the silencing of AKAP150 increased Akt phosphorylation and BK-beta1 expression in MOVAS cells treated with HG medium. The inhibition of Akt activity caused a decrease in BK-beta1 expression, and treatment with AKAP150 siRNA suppressed GSK3beta expression in the nuclei of MOVAS cells treated with HG. Knockout of AKAP150 reverses impaired BK channel-mediated vascular dysfunction through the Akt/GSK3beta signalling pathway in diabetes mellitus.