BACE1 and type 2 diabetes mellitus: We tested this hypothesis in 3 ways: firstly, by reducing BACE1 activity genetically and pharmacologically in mice and ascertaining how this modified diet-induced endothelial dysfunction; secondly, by increasing plasma Aβ levels, indirectly through overexpression of mutant human APP genes and directly by Aβ peptide infusion, to promote vascular dysfunction in mice; and thirdly, by cross-sectionally examining the association between plasma Aβ levels and endothelial function in patients with T2D.