Mist1-null mice are resistant to streptozotocin-induced β cell damage

Streptozotocin (STZ), a pancreatic β cell toxin, is used to induce diabetic conditions by targeting the Glut-2 transporter. We have recently identified decreased Glut-2 expression in β cells of mice lacking the transcription factor Mist1 (Mist1KO). Given the loss in Glut-2 expression, we examined whether Mist1KO β cells have an increased resistance to STZ. Mist1KO and wild-type (WT) female mice received a single 100 or 200 mg/kg injection of STZ, and resting glucose levels and islet morphology were assayed 3-7 days after injection. Ten-month-old Mist1KO mice have less β cell damage when exposed to high levels of STZ while 2-month-old Mist1KO mice exhibit a dose-dependent resistance. Surprisingly, Mist1KO mice still have elevated fasting glucose levels when compared to WT mice. These results suggest that while Mist1KO islets have increased resistance to STZ, additional effects outside of β cell loss alter blood glucose homeostasis.