These data suggest that the metabolic impacts of HFHC diet are sufficient to overcome the compensatory capacity of β cells after STZ exposure, a response that is known to be reduced in overt type 2 diabetic humans (Butler et al., 2007) and is similar to the insulin-resistant rat models, where hyperglycemia results from low doses of STZ that would otherwise have no impact on glucose metabolism in normal wild-type rats (Reaven and Ho, 1991). Here, INS is linked to Hyperglycemia.