INS and Hyperglycemia: Genetic models of hyperglycemia were developed to induce hyperglycemia without the use of toxic compounds[47, 48].These include the mouse models NOD-Rag1null Prf1null Ins2Akita,NOD-Rag1null IL-2rynullIns2Akita, etc. The advantages of these modelsinclude: 1) spontaneous development of hyperglycemia without the use of toxicagents; 2) persistent and severe hyperglycemia; 3) no return to normoglycemia,due to endogenous mouse islets; 4) no need for exogenous insulin to prevent thedevelopment of metabolic decompensation and death.