Fazio Elena N, Pin Christopher L
Department of Paediatrics, University of Western Ontario, Children's Health Research Institute, 800 Commissioners Road E., London, Ont., Canada N6C 2V5.
Biochem Biophys Res Commun. 2007 Feb 16;353(3):823-8. doi: 10.1016/j.bbrc.2006.12.110. Epub 2006 Dec 22.
Streptozotocin (STZ), a pancreatic beta cell toxin, is used to induce diabetic conditions by targeting the Glut-2 transporter. We have recently identified decreased Glut-2 expression in beta cells of mice lacking the transcription factor Mist1 (Mist1(KO)). Given the loss in Glut-2 expression, we examined whether Mist1(KO) beta cells have an increased resistance to STZ. Mist1(KO) 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 Mist1(KO) mice have less beta 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 beta cell loss alter blood glucose homeostasis.
链脲佐菌素（STZ）是一种胰腺β细胞毒素，通过作用于葡萄糖转运蛋白2（Glut-2）来诱导糖尿病状态。我们最近发现，在缺乏转录因子Mist1（Mist1基因敲除小鼠，Mist1(KO)）的小鼠β细胞中，Glut-2的表达降低。鉴于Glut-2表达的缺失，我们研究了Mist1(KO)β细胞对STZ的抗性是否增强。给Mist1(KO)和野生型（WT）雌性小鼠单次注射100或200mg/kg的STZ，并在注射后3 - 7天检测静息血糖水平和胰岛形态。10月龄的Mist1(KO)小鼠在暴露于高剂量STZ时β细胞损伤较少，而2月龄的Mist1(KO)小鼠表现出剂量依赖性抗性。令人惊讶的是，与WT小鼠相比，Mist1(KO)小鼠的空腹血糖水平仍然升高。这些结果表明，虽然Mist1(KO)胰岛对STZ的抗性增强，但β细胞丢失之外的其他效应改变了血糖稳态。
