TY - JOUR
T1 - Mitochondrion-driven nephroprotective mechanisms of novel glucose lowering medications
AU - Afsar, Baris
AU - Hornum, Mads
AU - Afsar, Rengin Elsurer
AU - Ertuglu, Lale A.
AU - Ortiz, Alberto
AU - Covic, Adrian
AU - van Raalte, Daniel H.
AU - Cherney, David Z. I.
AU - Kanbay, Mehmet
N1 - Funding Information:
MK gratefully acknowledge use of the services and facilities of the Koç University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget.”
Funding Information:
MK gratefully acknowledge use of the services and facilities of the Ko? University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget.?, Compliance with Ethical Standards. This study was not funded by any grant. This article does not contain any studies with human participants or animals performed by any of the authors.
Publisher Copyright:
© 2021
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Therapy for diabetic kidney disease (DKD) is undergoing a revolution with the realization that some glucose-lowering 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 1α 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.
AB - Therapy for diabetic kidney disease (DKD) is undergoing a revolution with the realization that some glucose-lowering 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 1α 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.
KW - Diabetes
KW - Diabetic kidney disease
KW - GLP-1 receptor activators
KW - Mitochondria
KW - Organ protection
KW - SGLT2 inhibitors
UR - https://www.scopus.com/pages/publications/85102243295
U2 - 10.1016/j.mito.2021.02.016
DO - 10.1016/j.mito.2021.02.016
M3 - Review article
C2 - 33677060
SN - 1567-7249
VL - 58
SP - 72
EP - 82
JO - Mitochondrion
JF - Mitochondrion
ER -
SDG 3 Good Health and Well-being