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

Abstract: 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 (Mist1 KO ). Given the loss in Glut-2 expression, we examined whether Mist1 KO β cells have an increased resistance to STZ. Mist1 KO and wild-type (WT) female mice received a single 100 or 200mg/kg injection of STZ, and resting glucose levels and islet morphology were assayed 3–7 days after injection. Ten-month-old Mist1 KO mice have less β cell damage when exposed to high levels of STZ while 2-month-old Mist1 KO mice exhibit a dose-dependent resistance. Surprisingly, Mist1 KO mice still have elevated fasting glucose levels when compared to WT mice. These results suggest that while Mist1 KO islets have increased resistance to STZ, additional effects outside of β cell loss alter blood glucose homeostasis. [Copyright &y& Elsevier]