Type 1 diabetes (T1D) is a disease characterized by destruction of the insulin-producing beta cells. Currently, there remains a critical gap in our understanding of how to reverse or prevent beta cell loss in individuals with T1D. Previous studies in mice discovered that pharmacologically inhibiting polyamine biosynthesis using difluoromethylornithine (DFMO) resulted in preserved beta cell function and mass. Similarly, treatment of non-obese diabetic mice with the tyrosine kinase inhibitor Imatinib mesylate reversed diabetes. The promising findings from these animal studies resulted in the initiation of two separate clinical trials that would repurpose either DFMO (NCT02384889) or Imatinib (NCT01781975) and determine effects on diabetes outcomes; however, whether these drugs directly stimulated beta cell growth remained unknown. To address this, we used the zebrafish model system to determine pharmacological impact on beta cell regeneration. After induction of beta cell death, zebrafish embryos were treated with either DFMO or Imatinib. Neither drug altered whole-body growth or exocrine pancreas length. Embryos treated with Imatinib showed no effect on beta cell regeneration; however, excitingly, DFMO enhanced beta cell regeneration. These data suggest that pharmacological inhibition of polyamine biosynthesis may be a promising therapeutic option to stimulate beta cell regeneration in the setting of diabetes.

1 型糖尿病 (T1D) 是一种以产生胰岛素的 β 细胞破坏为特征的疾病。目前，我们对如何逆转或预防 T1D 患者的 β 细胞丢失的理解仍然存在重大差距。先前对小鼠的研究发现，使用二氟甲基鸟氨酸 (DFMO) 从药理学上抑制多胺生物合成可保留 β 细胞的功能和质量。类似地，用酪氨酸激酶抑制剂甲磺酸伊马替尼治疗非肥胖糖尿病小鼠可逆转糖尿病。这些动物研究的有希望的发现导致了两项独立的临床试验的启动，这些试验将重新利用 DFMO (NCT02384889) 或伊马替尼 (NCT01781975) 并确定对糖尿病结果的影响；然而，这些药物是否直接刺激了 β 细胞的生长仍然未知。为了解决这个问题，我们使用斑马鱼模型系统来确定对 β 细胞再生的药理影响。诱导β细胞死亡后，斑马鱼胚胎用DFMO或伊马替尼处理。两种药物均未改变全身生长或外分泌胰腺长度。用伊马替尼处理的胚胎对 β 细胞再生没有影响；然而，令人兴奋的是，DFMO 增强了 β 细胞再生。这些数据表明，多胺生物合成的药理学抑制可能是在糖尿病环境中刺激 β 细胞再生的有希望的治疗选择。用伊马替尼处理的胚胎对 β 细胞再生没有影响；然而，令人兴奋的是，DFMO 增强了 β 细胞再生。这些数据表明，多胺生物合成的药理学抑制可能是在糖尿病环境中刺激 β 细胞再生的有希望的治疗选择。用伊马替尼处理的胚胎对 β 细胞再生没有影响；然而，令人兴奋的是，DFMO 增强了 β 细胞再生。这些数据表明，多胺生物合成的药理学抑制可能是在糖尿病环境中刺激 β 细胞再生的有希望的治疗选择。