Insulin‐deficient (type 1) diabetes is treated by providing insulin to maintain euglycemia. The current standard of care is a quasi‐closed loop integrating automated insulin delivery with a continuous glucose monitoring sensor. Cell replacement technologies are advancing as an alternative treatment and have been tested as surrogates to cadaveric islets in transplants. In addition, immunomodulatory treatments to delay the onset of type 1 diabetes in high‐risk (stage 2) individuals have gained regulatory approval. We have pioneered a cell conversion approach to restore insulin production through pharmacological conversion of intestinal epithelial cells into insulin‐producing cells. We have advanced this approach along a translational trajectory through the discovery of small molecule forkhead box protein O1 inhibitors. When administered to different rodent models of insulin‐deficient diabetes, these inhibitors have resulted in robust glucose‐lowering responses and generation of insulin‐producing cells in the gut epithelium. We review past work and delineate a path to human clinical trials.

中文翻译：

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通过将肠上皮细胞转化为胰岛素产生细胞来治疗糖尿病

胰岛素缺乏（1 型）糖尿病的治疗方法是提供胰岛素以维持血糖正常。目前的护理标准是将自动胰岛素输送与连续血糖监测传感器集成的准闭环。细胞替代技术作为一种替代疗法正在不断发展，并已作为移植中尸体胰岛的替代品进行了测试。此外，用于延迟高危（2 期）个体 1 型糖尿病发病的免疫调节治疗已获得监管部门的批准。我们开创了一种细胞转化方法，通过将肠上皮细胞药理学转化为胰岛素产生细胞来恢复胰岛素的产生。通过发现小分子叉头盒蛋白 O1 抑制剂，我们沿着转化轨迹推进了这种方法。当对不同的胰岛素缺乏型糖尿病啮齿动物模型进行给药时，这些抑制剂会产生强烈的降糖反应，并在肠道上皮细胞中产生胰岛素产生细胞。我们回顾了过去的工作并描绘了人类临床试验的路径。