INS and type 1 diabetes mellitus: The Akita (Ins2Akita+/−) mouse, a spontaneous diabetes model for early stage of DR (type I diabetes), is caused by a missense mutation in the diabetogenic Insulin 2 gene (Ins2) and is characterized by a rapid onset of hyperglycemia and hypoinsulinemia and marked reduction of insulin secretion by 4 weeks of age [36].