Functions and Mechanisms of Diabetes-Linked Transcription Factors

Transcription factors are significant regulators of gene expression in most biological processes related to diabetes, including beta cell (β-cell) development, insulin secretion and glucose metabolism. Dysregulation of transcription factor expression or abundance has been closely associated with the pathogenesis of type 1 and type 2 diabetes, including pancreatic and duodenal homeobox 1 (PDX1), neurogenic differentiation 1 (NEUROD1), and forkhead box protein O1 (FOXO1). Gene expression is regulated at the transcriptional level by transcription factor binding, epigenetically by DNA methylation and chromatin remodelling, and post-transcriptional mechanisms, including alternative splicing and microRNA (miRNA). Recent data indicate a central role for transcription factors in pancreatic β-cell failure in the context of systemic insulin resistance and chronic inflammation. Therapeutic modulation of transcription factor abundance via gene therapy, small-molecule pharmacology, and epigenetic therapies holds great promise for β-cell restoration and metabolic normalisation. However, further clinical translation will require targeted delivery to appropriate tissues, minimising off-target effects and ensuring long-term safety. This review focuses on the involvement of pancreatic β-cells and transcription factors in diabetes development and their therapeutic implications, intending to develop and consolidate a basis for further research in this area and for the treatment of diabetes in the future.