Mitochondrion-driven nephroprotective mechanisms of novel glucose lowering medications.

Afsar B., Hornum M., Afsar R. E. , Ertuglu L. A. , Ortiz A., Covic A., ...More

Mitochondrion, vol.58, pp.72-82, 2021 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 58
  • Publication Date: 2021
  • Doi Number: 10.1016/j.mito.2021.02.016
  • Journal Name: Mitochondrion
  • Journal Indexes: Science Citation Index Expanded, Scopus, Academic Search Premier, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.72-82
  • Keywords: Diabetes, Diabetic kidney disease, Mitochondria, Organ protection, SGLT2 inhibitors, GLP-1 receptor activators, GLUCAGON-LIKE PEPTIDE-1, FATTY LIVER-DISEASE, KIDNEY-DISEASE, INHIBITION, EMPAGLIFLOZIN, LIRAGLUTIDE, HYPOXIA, HEART, APOPTOSIS, AUTOPHAGY


Therapy for diabetic kidney disease (DKD) is undergoing a revolution with the realization that some glucoselowering drugs have nephroprotective actions that may be intrinsic to the drugs and not dependent on the impact on diabetes control, as demonstrated with the sodium glucose co-transporter-2 (SGLT-2) inhibitors. Mitochondria are a critical factor required for the maintenance of kidney function, given its high energy demanding profile, with extensive use of adenosine triphosphate (ATP). Consequently, deficiency of the master regulator of mitochondrial biogenesis peroxisome proliferator-activated receptor gamma coactivator 1 alpha predisposes to kidney disease. Perhaps as a result of key role of mitochondria in fundamental cellular functions, mitochondrial dysfunction may play a role in the pathogenesis of common conditions such as DKD. Finding pharmacological agents to influence this pathway could therefore lead to early implementation of therapy. Importantly, glucose-lowering drugs such as glucagon-like peptide-1 receptor activators and SGLT2 inhibitors have kidney and/or cardioprotective actions in patients with diabetes. Accumulating evidence from preclinical studies has suggested a protective effect of these drugs that is in part mediated by normalizing mitochondrial function. We now critically review this evidence and discuss studies needed to confirm mitochondrial protective benefits across a range of clinical studies.