6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3: A potential target in the development of diabetes and its complications.

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a bifunctional enzyme involved in the production and breakdown of fructose-2,6-bisphosphate (F-2,6-BP) and serves as a key regulator of glucose metabolism. It is closely implicated in the progression of diabetes and its associated complications, including diabetic cardiomyopathy (DCM), diabetic kidney disease (DKD), and diabetic retinopathy (DR). PFKFB3 mediates diabetes-induced organ damage through its effects on immune-inflammatory responses, fibrosis, vascular dysfunction, as well as β-cells function and survival. In this review, we highlight the bidirectional regulatory role of PFKFB3 in diabetes and its complications and explore the therapeutic potential of PFKFB3 inhibitors for managing diabetes and its related complications.