Exosomal miR-375-3p as a mediator of pancreas-liver crosstalk in impaired hepatic glycogenesis

Type 2 diabetes mellitus is a complex metabolic disorder characterized by impaired insulin secretion, insulin resistance, and dysregulated inter-organ communication. Beyond classical endocrine signaling, exosomes have recently emerged as critical mediators of crosstalk between pancreatic β cells and peripheral metabolic tissue. In a recent study<i>,</i> Xu <i>et al</i> demonstrated that hepatocytes can receive exosomal miR-375-3p derived from pancreatic β-cells, which suppresses the Rbpj region and consequently impairing hepatic glycogenesis. These findings provide novel mechanistic insights into how glucotoxic β cells influence hepatic glucose metabolism independently of insulin secretion. Notably, this study highlights exosomal miR-375-3p as a potential biomarker and therapeutic target for metabolic diseases. However, clinical validation in human cohorts and assessment of long-term metabolic outcomes are still required. A deeper understanding of exosome-mediated communication between the pancreas and liver may ultimately pave the way for new strategies to restore metabolic homeostasis and mitigate disease-related complications.