Metabolic Analysis and Renal Protective Effects of Linagliptin and Empagliflozin in Alport Syndrome
Abstract
KEY POINTS: Linagliptin reduces kidney function decline and extends lifespan in Alport syndrome mice. Inhibiting the generation of glucose metabolites could serve as a potential therapeutic strategy for the treatment of Alport syndrome.
BACKGROUND: We previously demonstrated that empagliflozin (Empa), a sodium-glucose cotransporter-2 inhibitor, reduces intrarenal lipid accumulation and slows kidney function decline in experimental Alport syndrome (AS). In this study, we aimed to evaluate the renal protective benefits of linagliptin (Lina), a dipeptidyl peptidase-4 inhibitor in AS, and compare it with Empa.
METHODS: Metabolite distribution in kidney cortices was assessed using mass spectrometry imaging. We examined albuminuria and histological changes in kidneys from AS mice treated with Lina and/or Empa or vehicle.
RESULTS: Several metabolites, including adrenic acid and glucose, were increased in renal cortices of AS mice compared with wild-type (WT) mice, whereas eicosapentaenoic acid levels were decreased. In addition, a redistribution of adrenic acid from the glomerular compartment in WT mice to the tubulointerstitial compartment in AS mice was observed. Both Lina and Empa treatments were found to reduce albuminuria to extend the survival of AS mice for about 10 days and to decrease glomerulosclerosis and tubulointerstitial fibrosis compared with WT mice. There were no significant differences with regard to the renal phenotype observed between Empa- and Lina-treated AS…
Read the paper
Related studies
- The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity
- Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism
- Isorhamnetin Reduces Glucose Level, Inflammation, and Oxidative Stress in High-Fat Diet/Streptozotocin Diabetic Mice Model
- Modulating Sirtuin Biology and Nicotinamide Adenine Diphosphate Metabolism in Cardiovascular Disease—From Bench to Bedside
- Characterization of the SGLT2 Interaction Network and Its Regulation by SGLT2 Inhibitors: A Bioinformatic Analysis
- Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.