CBS and Hyperglycemia: To investigate individual and synergistic effect of hyperglycemia and HHcy, we cross-bred Akita with CBS+/- to obtain four types of offspring: Ins2+/+/CBS+/+ (WT); Ins2+/-, CBS+/+ (Akita); Ins2+/+/CBS+/- (CBS mutant) and Ins2+/-/CBS+/- (double knock out).