Metabolic Modulation of Type 2 Diabetes Mellitus by 1-Deoxynojirimycin: A Multifaceted Approach.

Type 2 diabetes mellitus (T2DM) represents a significant global health burden. The natural alkaloid, 1-Deoxynojirimycin (DNJ), abundant in mulberry (Morus alba L.), offers a promising bioactive approach to its early management. This review comprehensively summarises the multifaceted roles of DNJ in modulating the core pathophysiological dysfunctions of T2DM, including impaired glucose and lipid metabolism, insulin resistance (IR), and dysbiosis of gut microbiota. Specifically, DNJ exerts its therapeutic effects by regulating various pathways involved in glucose and lipid metabolism (e.g., phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) and AMP-activated protein kinase (AMPK) pathways), enhancing insulin sensitivity, modulating the gut microbiota, and upregulating transporter proteins. We highlight emerging methodologies, such as network pharmacology, which underscore the pivotal role of the PI3K/AKT and AMPK signalling pathways as primary targets of DNJ in T2DM management. Although this review elucidates multifaceted mechanisms of DNJ in T2DM management, it also identifies critical research gaps, particularly concerning its effects on pancreatic cells, obesity-related T2DM, and mitochondrial energy metabolism. Further investigation in these areas is crucial for fully understanding DNJ's preventive and therapeutic potential and for the development of related functional foods.