Type 2 diabetic patients with severe insulin resistance have lower UBC9 protein expression in skeletal muscle.227 Mice depleted of the unique SUMO conjugation E2 enzyme UBC9 in pancreatic beta cells spontaneously develop diabetes because of β cell death occurring as a result of the accumulation of reactive oxygen species.238 Gli-similar 3 (Glis3) is an insulin-regulated-associated transcription factor. The gene discussed is GLIS3; the disease is diabetes mellitus.