Glucagon like peptide-1 modulates urinary sodium excretion in diabetic kidney disease via ENaC activation.

ABSTRACT: Diabetic kidney disease (DKD) is a leading cause of end stage kidney disease. Elevated salt sensitivity by epithelial sodium channel (ENaC) overexpression may be a residual risk factor for DKD. We found that combination therapy of linagliptin (LINA) to empagliflozin (EMPA), but not EMPA alone decreased phosphorylated Nedd4-2 (p-Nedd4-2) and ENaC levels in DKD rats in association with the increased urinary sodium excretion (USE). More extensive renoprotective effects were observed by the combination therapy of LINA and EMPA in deoxycorticosterone and high salt-treated mice. Acute injection experiments showed time-lagged administration of LINA to EMPA increased USE, and its effect sustained until 3 h. High salt and high glucose increased p-Nedd4-2 and ENaC levels in cultured distal tubules,

SUBMITTER: Kodama G 

PROVIDER: S-EPMC11968945 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature