This protocol details the oral glucose tolerance test in mice. This is performed on C57Bl6, transgenic SENP1 KO and ZMIZ1 KO mouse models. Typically GTT's are done at 12 weeks of age. Following the GTT on chow diet, some mice are put on high fat diet for the next 10 weeks. Subsequent glucose tolerance tests are performed following 2 days, 4 weeks and 8 weeks of high fat diet.Insulin tolerance test can also be performed. Once the in vivo studies are complete, the pancreas or islets are isolated for further ex vivo experiments.