The exosome-PI3K/Akt-autophagy axis in diabetic vascular complications: Mechanisms and implications

Diabetic vascular complications (DVCs) are among the most serious issues faced by individuals with diabetes. The pathogenesis of DVC involves various pathological processes, including lipid metabolism disorders, inflammatory responses, apoptosis and neovascularisation. While exosomes, the phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/Akt) pathway and autophagy have been extensively studied individually in DVC, a gap exists in understanding their integrative crosstalk and feedback mechanisms as a cohesive regulatory network.

Based on a review of the literature, we analyse the individual and interactive roles of exosomes, the PI3K/Akt pathway and autophagy in DVC pathogenesis, with a focus on their integrative regulatory network.

Exosomes carrying specific miRNAs, proteins, and other bioactive molecules regulate intracellular autophagy via the PI3K/Akt pathway. At the same time, autophagy is bidirectionally regulated by the PI3K/Akt pathway. Through this mutual regulation, they collectively influence exosome biogenesis and secretion, which in turn modulates cell survival, proliferation, and inflammatory responses to maintain intracellular homeostasis. Both processes co-regulate cellular metabolic homeostasis and inflammatory responses through the PI3K/Akt pathway, affecting vascular endothelial function.

In this review, we propose the novel conceptual framework of the "exosome-PI3K/Akt-autophagy axis" and investigate the role and mechanism in DVC, aiming to provide novel therapeutic targets and strategies for its treatment.