San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, 20133 Milan, Italy.
Int J Mol Sci. 2019 Oct 8;20(19):4962. doi: 10.3390/ijms20194962.
An increasing body of evidence indicates that bio-energetic metabolism of T cells can be manipulated to control T cell responses. This potentially finds a field of application in the control of the T cell responses in autoimmune diseases, including in type 1 diabetes (T1D). Of the possible metabolic targets, Glut1 gained considerable interest because of its pivotal role in glucose uptake to fuel glycolysis in activated T cells, and the recent development of a novel class of small molecules that act as selective inhibitor of Glut1. We believe we can foresee a possible application of pharmacological Glut1 blockade approach to control autoreactive T cells that destroy insulin producing beta cells. However, Glut1 is expressed in a broad range of cells in the body and off-target and side effect are possible complications. Moreover, the duration of the treatment and the age of patients are critical aspects that need to be addressed to reduce toxicity. In this paper, we will review recent literature to determine whether it is possible to design a pharmacological Glut1 blocking strategy and how to apply this to autoimmunity in T1D.
越来越多的证据表明，T 细胞的生物能量代谢可以被操纵来控制 T 细胞的反应。这在控制自身免疫性疾病中的 T 细胞反应方面具有潜在的应用，包括 1 型糖尿病 (T1D)。在可能的代谢靶点中，Glut1 因其在激活的 T 细胞中摄取葡萄糖以提供糖酵解燃料的关键作用而引起了相当大的关注，并且最近开发了一类新型小分子，它们可以作为 Glut1 的选择性抑制剂。我们相信，我们可以预见通过药理学 Glut1 阻断方法来控制破坏胰岛素产生β细胞的自身反应性 T 细胞的可能性。然而，Glut1 在体内广泛表达，存在脱靶和副作用等可能的并发症。此外，治疗的持续时间和患者的年龄是需要解决的关键方面，以降低毒性。在本文中，我们将回顾最近的文献，以确定是否有可能设计一种药理学 Glut1 阻断策略，并将其应用于 T1D 的自身免疫。
