This protocol details the insulin tolerance test in mice. This is performed on C57Bl6, transgenic SENP1 KO and ZMIZ1 KO mouse models. Typically glucose tolerance tests (GTTs) are performed at 12 weeks of age, followed by an ITT 2 weeks later. Some mice are put on High Fat Diet and an ITT repeated following 10 weeks on High Fat Diet.Once the in vivo studies are complete, the pancreas or islets are isolated for further ex vivo experiments.