Abstract:
Type 1 diabetes (T1D) is a common autoimmune disease in which dysregulated glucose metabolism is a key feature. T1D is both poorly understood and in need of improved therapeutics. Hypoxia is frequently encountered in multiple tissues in T1D patients including the pancreas and sites of diabetic complications. Hypoxia-inducible factor (HIF)-1, a ubiquitous master regulator of the adaptive response to hypoxia, promotes glucose metabolism through transcriptional and non-transcriptional mechanisms and alters disease progression in multiple preclinical T1D models. However, how HIF-1 activation in β-cells of the pancreas and immune cells (two key cell types in T1D) ultimately affects disease progression remains controversial. We discuss recent advances in our understanding of the role of hypoxia/HIF-1-induced glycolysis in T1D and explore the possible use of drugs targeting this pathway as potential new therapeutics.
摘要:
1型糖尿病(T1D)是一种常见的自身免疫性疾病,其中葡萄糖代谢失调是关键特征。对T1D的了解很少,并且需要改进的治疗剂。在T1D患者的多个组织中经常遇到缺氧,包括胰腺和糖尿病并发症的部位。缺氧诱导因子(HIF)-1,一种普遍存在的缺氧适应性反应的主要调节因子,在多个临床前T1D模型中,通过转录和非转录机制促进葡萄糖代谢并改变疾病进展。然而,胰腺β细胞和免疫细胞(T1D中的两种关键细胞类型)中的HIF-1激活如何最终影响疾病进展仍存在争议.我们讨论了我们对缺氧/HIF-1诱导的糖酵解在T1D中的作用的理解的最新进展,并探讨了靶向该途径的药物作为潜在的新疗法的可能用途。