Abstract
Diabetes mellitus is a complex metabolic disorder characterized by hyperglycemia due to impaired insulin production, action, or both. The Pancreas and Liver play central roles in glucose regulation, and their dysfunction is critical to the onset and progression of specific types of diabetes, including type 2 diabetes and certain forms of monogenic diabetes. While these organs have distinct physiological roles, they originate from the foregut endoderm and share key developmental regulators and signaling pathways. This review explores the overlapping transcription factors and genes that are essential for both pancreatic and hepatic development and function. These dual-role genes not only govern early organogenesis but are also implicated in diabetes pathogenesis, underscoring their significance in metabolic homeostasis. We highlight how interorgan signaling, particularly between hepatokines and pancreatic islet cells, contributes to the maintenance or disruption of glucose metabolism. Furthermore, we discuss the clinical implications of these shared pathways, emphasizing how insights from developmental biology can inform precision diagnostics and therapeutic strategies for diabetes. Finally, we consider how emerging tools, such as pluripotent stem cell-based disease models and gene editing and multi-omics approaches, are transforming our understanding of gene function and disease progression. By bridging the developmental and metabolic landscapes of the pancreas and liver, this review provides a comprehensive framework for uncovering novel regulators of diabetes and paves the way toward targeted, personalized treatment strategies.