PMID- 26733332
OWN - NLM
STAT- MEDLINE
DCOM- 20170822
LR  - 20211204
IS  - 1724-6059 (Electronic)
IS  - 1121-8428 (Linking)
VI  - 29
IP  - 6
DP  - 2016 Dec
TI  - Metformin modulates apoptosis and cell signaling of human podocytes under high 
      glucose conditions.
PG  - 765-773
AB  - Diabetic nephropathy, which is associated with loss of human (h) podocytes (PC), 
      is a major complication in diabetes mellitus. High-glucose modulates 
      AMP-activated protein kinase (AMPK) signaling and cell apoptosis. Metformin has 
      been demonstrated to reduce apoptosis and albuminuria in type 2 diabetes. Here, 
      we examined the effect of metformin on cell apoptosis and on pro-/anti-apoptotic 
      signaling in hPC. Expression analyses were done by real-time polymerase chain 
      reaction and western blotting. Moreover, a functional apoptosis assay was 
      performed in hPC. Determination of kinase activation by phosphorylation was done 
      via immunodetection analyses and digital quantification. We found that hPC 
      express organic cation transporter 1 which is the major uptake transporter of 
      metformin. High-glucose reduced AMPK phosphorylation and induced mammalian target 
      of rapamycin (mTOR) activation in podocytes, which was abolished and reversed by 
      pre-treatment with metformin. Furthermore, metformin reduced high-glucose-induced 
      podocytes apoptosis in a concentration-dependent manner. In summary, metformin 
      exhibits an anti-apoptotic impact on podocytes under high-glucose conditions via 
      activation of AMPK and inhibition of mTOR signaling. These data support a 
      beneficial effect of metformin in diabetic nephropathy.
FAU - Langer, Sebastian
AU  - Langer S
AD  - Klinische Pharmakologie und Toxikologie, CC04, Charite-Universitatsmedizin 
      Berlin, Chariteplatz 1, 10117, Berlin, Germany.
FAU - Kreutz, Reinhold
AU  - Kreutz R
AD  - Klinische Pharmakologie und Toxikologie, CC04, Charite-Universitatsmedizin 
      Berlin, Chariteplatz 1, 10117, Berlin, Germany.
FAU - Eisenreich, Andreas
AU  - Eisenreich A
AD  - Klinische Pharmakologie und Toxikologie, CC04, Charite-Universitatsmedizin 
      Berlin, Chariteplatz 1, 10117, Berlin, Germany. andreas.eisenreich@charite.de.
LA  - eng
PT  - Journal Article
DEP - 20160105
PL  - Italy
TA  - J Nephrol
JT  - Journal of nephrology
JID - 9012268
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Organic Cation Transporter 1)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Apoptosis/*drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Cytoprotection
MH  - Diabetic Nephropathies/genetics/metabolism/pathology/*prevention & control
MH  - Dose-Response Relationship, Drug
MH  - Glucose/*toxicity
MH  - Humans
MH  - Hypoglycemic Agents/metabolism/*pharmacology
MH  - Metformin/metabolism/*pharmacology
MH  - Organic Cation Transporter 1/genetics/metabolism
MH  - Phosphorylation
MH  - Podocytes/*drug effects/metabolism/pathology
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Diabetic nephropathy
OT  - Glucose
OT  - Podocytes
EDAT- 2016/10/27 06:00
MHDA- 2017/08/23 06:00
CRDT- 2016/01/07 06:00
PHST- 2015/05/15 00:00 [received]
PHST- 2015/12/15 00:00 [accepted]
PHST- 2016/10/27 06:00 [pubmed]
PHST- 2017/08/23 06:00 [medline]
PHST- 2016/01/07 06:00 [entrez]
AID - 10.1007/s40620-015-0258-1 [pii]
AID - 10.1007/s40620-015-0258-1 [doi]
PST - ppublish
SO  - J Nephrol. 2016 Dec;29(6):765-773. doi: 10.1007/s40620-015-0258-1. Epub 2016 Jan 
      5.