The sole inactivation of <i>Arx</i> in α-cells can induce a regeneration of the β-like cell mass following streptozotocin treatment.

1.5mDox+ IndGlu-ArxKO::Rosa animals were treated with streptozotocin or sodium citrate (A) and their pancreatic composition was examined by immunohistochemistry. Next to the classical loss of β-cells upon high-dose streptozotocin treatment (data not shown), few insulin-producing cells could be detected as early as 10 days post-streptozotocin treatment (B). Interestingly, after 100 days of Dox treatment, the islets in streptozotocin-treated animals appeared reformed and displayed β-gal+ cells located in the core of the islet (C). Further examination demonstrated that such β-gal+ cells were insulin+ (D–E), suggesting that Arx inactivation in glucagon-expressing cells allows their regeneration and conversion to functional insulin+ cells capable of counteracting the effects of streptozotocin. (Stz: Streptozotocin, each photograph is representative of at least three independent animals).