PMID- 27627216
OWN - NLM
STAT- MEDLINE
DCOM- 20170508
LR  - 20220318
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 232
IP  - 4
DP  - 2017 Apr
TI  - Nephroprotective Effects of Metformin in Diabetic Nephropathy.
PG  - 731-742
LID - 10.1002/jcp.25598 [doi]
AB  - Metformin, a well-known anti-diabetic agent, is very effective in lowering blood 
      glucose in patients with type 2 diabetes with minimal side-effects. Metformin is 
      also being recommended in the treatment of obesity and polycystic ovary syndrome. 
      Metformin elicits its therapeutic effects mainly via activation of AMP-activated 
      kinase (AMPK) pathway. Renal cells under hyperglycemic or proteinuric conditions 
      exhibit inactivation of cell defense mechanisms such as AMPK and autophagy, and 
      activation of pathologic pathways such as mammalian target of rapamycin (mTOR), 
      endoplasmic reticulum (ER) stress, epithelial-to-mesenchymal transition (EMT), 
      oxidative stress, and hypoxia. As these pathologic pathways are intertwined with 
      AMPK signaling, the potential benefits of metformin therapy in patients with type 
      2 diabetes would extend beyond its anti-hyperglycemic effects. However, since 
      metformin is eliminated unchanged through the kidneys and some studies have shown 
      the incidence of lactic acidosis with its use during severe renal dysfunction, 
      the use of metformin was contraindicated in patients with renal disease until 
      recently. With more studies indicating the relatively low incidence of lactic 
      acidosis and revealing the additional benefits with metformin therapy, the US FDA 
      has now approved metformin to be administered in patients with established renal 
      disease based on their renal function. The purpose of this review is to highlight 
      the various mechanisms by which metformin protects renal cells that have lost its 
      functionality in a diabetic or non-diabetic setting and to enlighten the 
      advantages and therapeutic potential of metformin as a nephroprotectant for 
      patients with diabetic nephropathy and other non-diabetic forms of chronic kidney 
      disease. J. Cell. Physiol. 232: 731-742, 2017. (c) 2016 Wiley Periodicals, Inc.
CI  - (c) 2016 Wiley Periodicals, Inc.
FAU - Ravindran, Sreenithya
AU  - Ravindran S
AD  - College of Pharmacy, Qatar University, Doha, Qatar.
FAU - Kuruvilla, Vinitha
AU  - Kuruvilla V
AD  - College of Pharmacy, Qatar University, Doha, Qatar.
FAU - Wilbur, Kerry
AU  - Wilbur K
AD  - College of Pharmacy, Qatar University, Doha, Qatar.
FAU - Munusamy, Shankar
AU  - Munusamy S
AD  - College of Pharmacy, Qatar University, Doha, Qatar.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160926
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Protective Agents)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Animals
MH  - Diabetic Nephropathies/*drug therapy
MH  - Endoplasmic Reticulum Stress/drug effects
MH  - Humans
MH  - Metformin/pharmacokinetics/*therapeutic use
MH  - Oxidative Stress/drug effects
MH  - Protective Agents/pharmacokinetics/pharmacology/*therapeutic use
MH  - Signal Transduction/drug effects
EDAT- 2016/09/15 06:00
MHDA- 2017/05/10 06:00
CRDT- 2016/09/15 06:00
PHST- 2016/09/09 00:00 [received]
PHST- 2016/09/12 00:00 [accepted]
PHST- 2016/09/15 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2016/09/15 06:00 [entrez]
AID - 10.1002/jcp.25598 [doi]
PST - ppublish
SO  - J Cell Physiol. 2017 Apr;232(4):731-742. doi: 10.1002/jcp.25598. Epub 2016 Sep 
      26.