VCAM1 and endothelial dysfunction: Furthermore, C-peptide combats high glucose-induced endothelial dysfunction by reducing NF-κB activation, potentially due to C-peptide induced phosphorylation of protein substrates in the cytoplasm or its interaction with NF-κB p65/p50 subunit, preventing DNA binding, impacting the expression of VCAM-1 and the secretion of MCP-1 and IL-8 (72, 73).