Work

The biology of PKM2 in the metabolism and senescence in diabetic kidney disease

Year: 2025

Type: article

Abstract: Diabetic kidney disease (DKD) is one of the most common causes of chronic kidney disease that leads to end-stage kidney disease, and its progression is closely linked to metabolic stress within renal tubular cells. Under long-term hyperglycemia, cells shift their glucose metabolism from normal oxidative phosphorylation toward glycolysis. This change is driven in part by the conversion of pyruvate kinase M2 (PKM2) from its active tetramer form to the less active dimer form. The PKM2 dimer slows pyruvate production and promotes lactate accumulation, leading to redox imbalance and activation of stress pathways such as HIF-1α, STAT3, and NF-κB. These signaling events enhance cellular senescence and inflammation, which further aggravate tubular injury and fibrosis. Growing evidence suggests that stabilizing PKM2 in its tetrameric state or blocking its nuclear translocation can restore metabolic balance and reduce renal damage. Targeting PKM2 dimer-dependent metabolic reprogramming may therefore represent a promising therapeutic approach to slow or reverse the progression of DKD.

Source: Journal of Diabetes Investigation

DOI: 10.1111/jdi.70231

Authors: Md. Imrul Kayes, Keizo Kanasaki

Institutions: Shimane University, University of Shimane

Language: English

Topic: Chronic Kidney Disease and Diabetes

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,850