PMID- 12649541
OWN - NLM
STAT- MEDLINE
DCOM- 20030723
LR  - 20131121
IS  - 1121-8428 (Print)
IS  - 1121-8428 (Linking)
VI  - 16
IP  - 1
DP  - 2003 Jan-Feb
TI  - Regulation of glucose transporters in human peritoneal mesothelial cells.
PG  - 103-9
AB  - BACKGROUND: Risk factors for peritoneal fibrosis and mesothelial cell (MsC) 
      injury in CAPD are infections and bioincompatibility of the dialysate, including 
      high glucose concentrations. To study a potential link between dialysate and 
      glucose toxicity in MsC, we investigated the expression of facilitative glucose 
      transporters (GLUT), which could contribute to glucose toxicity. METHODS: After 
      induction of cell differentiation, MsC were incubated in regular medium or medium 
      with 60 mM D-glucose, 30 mM glucose plus 30 mM mannitol, 60 mM mannitol, PD 
      effluent, or with a cytokine mix. Expression of GLUT1, GLUT3, SGLT and GAPDH/L32 
      was studied by RNase protection assay. MsC were incubated under identical 
      conditions with 14C-fluoro-deoxy-glucose for 30 minutes and glucose uptake was 
      measured. To estimate Vmax and Km, 14C-fluoro-deoxy-glucose uptake rates were 
      determined over a range of 0.6 to 10 mM unlabeled glucose. RESULTS: The cytokine 
      mix significantly stimulated GLUT1 expression (3-fold) and GLUT3 (1.7-fold). 
      There was a 1.4-fold increase in GLUT1 (p<0.05) and a 1.7-fold increase in GLUT3 
      (p<0.05) after incubation in high glucose but not in mannitol or PD-effluent 
      controls. Glucose uptake studies confirmed this increase after incubation in 30 
      mM (p<0.05) and 60 mM glucose solutions. Kinetic studies showed the Km was 
      approximately 3.7 mM for this transport. CONCLUSIONS: GLUT mRNA expression and 
      glucose uptake are induced by high ambient glucose concentrations and cytokines. 
      Unlike many other cells, MsC are not able to protect themselves from increased 
      glucose concentrations by downregulation of GLUTs. The intracellular glucose 
      concentration may therefore increase during CAPD, affecting growth factor 
      expression and glycosylation, and contributing to glucose toxicity.
FAU - Fischereder, Michael
AU  - Fischereder M
AD  - Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany. 
      michael.fischereder@klinik.uni-regensburg.de
FAU - Schroppel, Bernd
AU  - Schroppel B
FAU - Wiese, Patrick
AU  - Wiese P
FAU - Fink, Monika
AU  - Fink M
FAU - Banas, Bernhard
AU  - Banas B
FAU - Schmidbauer, Stefan
AU  - Schmidbauer S
FAU - Schlondorff, Detlef
AU  - Schlondorff D
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - J Nephrol
JT  - Journal of nephrology
JID - 9012268
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Glucose Transporter Type 3)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (SLC2A3 protein, human)
RN  - 3OWL53L36A (Mannitol)
RN  - 63231-63-0 (RNA)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Biological Transport, Active/drug effects/physiology
MH  - Cell Division/physiology
MH  - Cells, Cultured
MH  - Culture Media, Conditioned
MH  - Epithelial Cells/physiology
MH  - Fibrosis/etiology/pathology
MH  - Glucose/*pharmacology
MH  - Glucose Transporter Type 3
MH  - Humans
MH  - Kidney Failure, Chronic/therapy
MH  - Mannitol/*pharmacology
MH  - Membrane Glycoproteins/*metabolism
MH  - Monosaccharide Transport Proteins/*metabolism
MH  - *Nerve Tissue Proteins
MH  - Peritoneal Dialysis, Continuous Ambulatory/adverse effects
MH  - Peritoneal Diseases/etiology/pathology
MH  - Peritoneum/*cytology
MH  - Probability
MH  - RNA/analysis
MH  - Sensitivity and Specificity
EDAT- 2003/03/22 04:00
MHDA- 2003/07/24 05:00
CRDT- 2003/03/22 04:00
PHST- 2002/10/24 00:00 [received]
PHST- 2002/12/12 00:00 [accepted]
PHST- 2003/03/22 04:00 [pubmed]
PHST- 2003/07/24 05:00 [medline]
PHST- 2003/03/22 04:00 [entrez]
PST - ppublish
SO  - J Nephrol. 2003 Jan-Feb;16(1):103-9.