In fact, the results presented herein strongly suggest that in diabetic ZDF rats sitagliptin may derive its cytoprotective effects via two different type of influences: directly reducing apoptosis and promoting cell proliferation due to increase incretin availability; indirectly via metabolic effects, including amelioration of chronically elevated glucose and triglycerides, prevention of insulinopaenia and reduction of inflammation, thus protecting from deleterious effects derived from glucotoxicity, lipotoxicity and insulin resistance. Here, GCG is linked to Insulin resistance.