Work

Cdk5 Contributes to Diabetic Islet β Cell and Kidney Injury by Impairing Autophagy

Year: 2025

Type: article

Abstract: Insufficient insulin secretion due to islet β cell damage is a hallmark of diabetes mellitus. Diabetic nephropathy (DN) is a common microvascular complication of diabetes, and podocyte damage is the main cause of proteinuria in patients with DN. Over-activation of cyclin-dependent kinase 5 (Cdk5) is involved in the development of diabetes and its complications; however, the specific mechanism remains to be elucidated. The aim of this study was to investigate the role of Cdk5 in diabetic islet β cells and renal injury. Our results showed that Cdk5 expression was upregulated in diabetic mice, which induced attenuated autophagy and increased apoptosis of islet β cells, as well as decreased insulin secretion. Similarly, Cdk5 activation impaired autophagy and apoptosis of podocytes. Decreasing the expression of Cdk5 in diabetes and DN partially restored the autophagy of islet β cells and podocytes and reduced the damage to islet β cells and podocytes. In conclusion, Cdk5 is involved in islet β cell and podocyte damage in a high glucose environment; thus, targeting Cdk5 may be a significant therapeutic option for diabetes and its complications.

Source: The FASEB Journal

DOI: 10.1096/fj.202500483rrrrr