GLP-1 Receptor Agonists Alleviate Diabetic Kidney Injury via β-Klotho-Mediated Ferroptosis Inhibition.

ABSTRACT: Semaglutide (Smg), a GLP-1 receptor agonist (GLP-1RA), shows renal protective effects in patients with diabetic kidney disease (DKD). However, the exact underlying mechanism remains elusive. This study employs transcriptome sequencing and identifies β-Klotho (KLB) as the critical target responsible for the role of Smg in kidney protection. Smg treatment alleviates diabetic kidney injury by inhibiting ferroptosis in patients, animal models, and HK-2 cells. Notably, Smg treatment significantly increases the mRNA expression of KLB through the activation of the cyclic adenosine monophosphate (cAMP) signaling pathway, specifically through the phosphorylation of protein kinase A (PKA) and cAMP-response element-binding protein (CREB). Subsequently, the adenosine monophosphate-activated protein ki

SUBMITTER: Tian S 

PROVIDER: S-EPMC11775532 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature