APOE and diabetes mellitus: Thus, mouse studies evaluating diabetes-associated atherosclerosis rely on ApoE−/− or LDLR−/− mice, where hypercholesterolemia is combined with chronic hyperglycemia following beta-cell destruction by injection of streptozotocin (STZ) or viral infection (22) or by crossbreeding with mouse strains carrying a point mutation in the gene encoding insulin leading to a misfolding of the proinsulin 2 protein (Ins2+/Akita) (4, 23).