Implication of the putative T2D target VDAC1 in renal and vascular diabetic complications

Type 2 diabetes (T2D) is an increasing health problem worldwide in which most of the cases are secondary to obesity with dyslipidaemia, leading to altered organ function through glucolipotoxicity. T2D develops after years of prediabetes, with deranged blood glucose levels (glucotoxicity) in concert with lipotoxicity that can cause insulin resistance, resulting in diabetic organ complications, including dysfunction of pancreatic β-cells , cardiovascular endothelial cells (EC) and renal cells, among them podocytes.
In the present project we evaluate the possible consequence of VDAC1 overexpression and translocation of VDAC1 to the cell surface in podocytes and HUVECs, as well as the mechanisms behind this “miss‐targeting” phenomenon, induced by inflammatory cytokines with or without a combination with glucolipotoxicity.
Moreover, we will also investigate whether VDAC1 inhibitors could restore the altered function of podocytes and HUVEC cells directly and preventing cell dysfunction and apoptosis.