title: Glutamine treatment attenuates hyperglycemia-induced mitochondrial stress and apoptosis in umbilical vein endothelial cells.
abstract: OBJECTIVE
  The aim of this study was to determine the in vitro effect of glutamine and insulin on apoptosis, mitochondrial membrane potential, cell permeability, and inflammatory cytokines in hyperglycemic umbilical vein endothelial cells.
  
  
  METHODS
  Human umbilical vein endothelial cells were grown and subjected to glutamine and insulin to examine the effects of these agents on the hyperglycemic state. Mitochondrial function and the production of inflammatory cytokines were assessed using fluorescence analysis and multiple cytotoxicity assays. Apoptosis was analyzed by the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay.
  
  
  RESULTS
  Glutamine maintains the integrity of the mitochondria by reducing the cell permeability and cytochrome c levels and increasing the mitochondrial membrane potential. The cytochrome c level was significantly (p<0.005) reduced when the cells were treated with glutamine. An apoptosis assay revealed significantly reduced apoptosis (p<0.005) in the glutamine-treated cells. Moreover, glutamine alone or in combination with insulin modulated inflammatory cytokine levels. Interleukin-10, interleukin-6, and vascular endothelial growth factor were up-regulated while tumor necrosis factor-α was down-regulated after treatment with glutamine.
  
  
  CONCLUSIONS
  Glutamine, either alone or in combination with insulin, can positively modulate the mitochondrial stress and cell permeability in umbilical vein endothelial cells. Glutamine regulates the expression of inflammatory cytokines and maintains the balance of the mitochondria in a cytoprotective manner.
authors.affiliation: Faculty of Medicine, University of Malaya, Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Sher Zaman
authors.initials: SZ
authors.lastname: Safi
authors.affiliation: Faculty of Medicine, University of Malaya, Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Kalaivani
authors.initials: K
authors.lastname: Batumalaie
authors.affiliation: Faculty of Medicine, University of Malaya, Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Marzida
authors.initials: M
authors.lastname: Mansor
authors.affiliation: Faculty of Medicine, University of Malaya, Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Karuthan
authors.initials: K
authors.lastname: Chinna
authors.affiliation: Faculty of Medicine, University of Malaya, Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Syam
authors.initials: S
authors.lastname: Mohan
authors.affiliation: Faculty of Medicine, University of Malaya, Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Hamed
authors.initials: H
authors.lastname: Karimian
authors.affiliation: Faculty of Medicine, University of Malaya, Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Rajes
authors.initials: R
authors.lastname: Qvist
authors.affiliation: Faculty of Science, University of Malaya, Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Muhammad Aqeel
authors.initials: MA
authors.lastname: Ashraf
authors.affiliation: Faculty of Medicine, University of Malaya, Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Garcie Ong Siok
authors.initials: GO
authors.lastname: Yan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000032:analysis; D016207:Cytokines / Q000032:analysis / Q000187:drug effects; D004338:Drug Combinations; D005973:Glutamine / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D016207:Cytokines; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D007328:Insulin; D005973:Glutamine; D045304:Cytochromes c